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Sample records for anticancer agents isolated

  1. Alkaloids Isolated from Natural Herbs as the Anticancer Agents

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    Jin-Jian Lu

    2012-01-01

    Full Text Available Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery. Several alkaloids isolated from natural herbs exhibit antiproliferation and antimetastasis effects on various types of cancers both in vitro and in vivo. Alkaloids, such as camptothecin and vinblastine, have already been successfully developed into anticancer drugs. This paper focuses on the naturally derived alkaloids with prospective anticancer properties, such as berberine, evodiamine, matrine, piperine, sanguinarine, and tetrandrine, and summarizes the mechanisms of action of these compounds. Based on the information in the literature that is summarized in this paper, the use of alkaloids as anticancer agents is very promising, but more research and clinical trials are necessary before final recommendations on specific alkaloids can be made.

  2. ISOLATION AND CHARACTERIZATION OF BIOACTIVE PROTEIN FROM GREEN ALGAE Halimeda macrobola AS ANTIOXIDANT AND ANTICANCER AGENT

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    Ahmad, Ahyar

    2014-01-01

    A protein fraction isolated from green algae Halimeda macrobola taken from the sea of Selayar and Kapoposang Island inSouth Sulawesi was tested forantioxidant and anticancer properties.The protein was isolated using buffer Tris (hydroxymethyl) amino methane. Initial purification of protein uses conducted by using the fractionation method with ammonium sulphate, followed by a dialysis process. The protein concentration was determined by Lowry method. The antioxidant assay was done by using DP...

  3. Anticancer agent-based marine natural products and related compounds.

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    Chen, Jian-Wei; Wu, Qi-Hao; Rowley, David C; Al-Kareef, Ammar M Q; Wang, Hong

    2015-01-01

    Marine natural products constitute a huge reservoir of anticancer agents. Consequently during the past decades, several marine anticancer compounds have been isolated, identified, and approved for anticancer treatment or are under trials. In this article the sources, structure, bioactivities, mode of actions, and analogs of some promising marine and derived anticancer compounds have been discussed. PMID:25559315

  4. Anthracenedione Derivatives as Anticancer Agents Isolated from Secondary Metabolites of the Mangrove Endophytic Fungi

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    Jian-ye Zhang

    2010-04-01

    Full Text Available In this article, we report anticancer activity of 14 anthracenedione derivatives separated from the secondary metabolites of the mangrove endophytic fungi Halorosellinia sp. (No. 1403 and Guignardia sp. (No. 4382. Some of them inhibited potently the growth of KB and KBv200 cells, among which compound 6 displayed strong cytotoxicity with IC50 values of 3.17 and 3.21 μM to KB and KBv200 cells, respectively. Furthermore, we demonstrate that the mechanism involved in the apoptosis induced by compound 6 is probably related to mitochondrial dysfunction. Additionally, the structure-activity relationships of these compounds are discussed.

  5. Lappaol F, a novel anticancer agent isolated from plant arctium Lappa L.

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    Sun, Qing; Liu, Kanglun; Shen, Xiaoling; Jin, Weixin; Jiang, Lingyan; Sheikh, M Saeed; Hu, Yingjie; Huang, Ying

    2014-01-01

    In an effort to search for new cancer-fighting therapeutics, we identified a novel anticancer constituent, Lappaol F, from plant Arctium Lappa L. Lappaol F suppressed cancer cell growth in a time- and dose-dependent manner in human cancer cell lines of various tissue types. We found that Lappaol F induced G(1) and G(2) cell-cycle arrest, which was associated with strong induction of p21 and p27 and reduction of cyclin B1 and cyclin-dependent kinase 1 (CDK1). Depletion of p21 via genetic knockout or short hairpin RNA (shRNA) approaches significantly abrogated Lappaol F-mediated G(2) arrest and CDK1 and cyclin B1 suppression. These results suggest that p21 seems to play a crucial role in Lappaol F-mediated regulation of CDK1 and cyclin B1 and G(2) arrest. Lappaol F-mediated p21 induction was found to occur at the mRNA level and involved p21 promoter activation. Lappaol F was also found to induce cell death in several cancer cell lines and to activate caspases. In contrast with its strong growth inhibitory effects on tumor cells, Lappaol F had minimal cytotoxic effects on nontumorigenic epithelial cells tested. Importantly, our data also demonstrate that Lappaol F exhibited strong growth inhibition of xenograft tumors in nude mice. Lappaol F was well tolerated in treated animals without significant toxicity. Taken together, our results, for the first time, demonstrate that Lappaol F exhibits antitumor activity in vitro and in vivo and has strong potential to be developed as an anticancer therapeutic. PMID:24222662

  6. Bacteriocins as potential anticancer agents

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    Sukhraj eKaur; Sumanpreet eKaur

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have nonspecific toxicity towards normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeu...

  7. Bacteriocins as Potential Anticancer Agents

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    Kaur, Sumanpreet; Kaur, Sukhraj

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have non-specific toxicity toward normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeu...

  8. Anticancer agents from marine sponges.

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    Ye, Jianjun; Zhou, Feng; Al-Kareef, Ammar M Q; Wang, Hong

    2015-01-01

    Marine sponges are currently one of the richest sources of anticancer active compounds found in the marine ecosystems. More than 5300 different known metabolites are from sponges and their associated microorganisms. To survive in the complicated marine environment, most of the sponge species have evolved chemical means to defend against predation. Such chemical adaptation produces many biologically active secondary metabolites including anticancer agents. This review highlights novel secondary metabolites in sponges which inhibited diverse cancer species in the recent 5 years. These natural products of marine sponges are categorized based on various chemical characteristics. PMID:25402340

  9. Isolation and characterization of bioactive protein from green algae Halimeda macrobola acting as antioxidant and anticancer agent

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    Ahmad, Ahyar

    2014-01-01

    A protein fraction isolated from green algae Halimeda macrobola taken from the sea of Selayar and Kapoposang Island in South Sulawesi was tested for antioxidant and anticancer properties. The protein was isolated using buffer Tris (hydroxymethyl) amino methane. Initial purification of protein was conducted by using the fractionation method with ammonium sulphate, followed by dialysis process. Protein concentration was determined by Lowry method. Antioxidant assay was done by using DPPH method...

  10. A REVIEW: HERBS USED AS ANTICANCER AGENTS

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    Badri Nagarani

    2011-01-01

    Full Text Available Herbs are the plants which will have desirable odour, taste and other medical uses. Anti-cancer agents are effective in cancer treatment. Here an attempt has been made to review some herbs used for the prevention and treatment of cancer. These herbs were found for posses anticancer, cytotoxic or antioxidant activity in various pre-clinical or clinical studies. Cancer is a disease in which body cells become abnormal and divide without control. Cancer cell may invade nearby tissues and they may spread through the blood stream & lymphatic system to other parts of the body. The search for anticancer agents from the plant sources alkaloids in earnest in the 1950s such as Vincristine, Vinblastine and the isolation of cytotoxic Podophyllotoxins will reduce white blood cell count and caused bone marrow depression in rats. Roots, leaves, stem, root, bark and fruity of the plant herbs are used in the treatment of cancer. The dietary antioxidants having anti carcinogenic property are in demand. Identification and characterization of these anti-carcinogens in the diet can be used for reducing the risk of human cancer. Tea (Camellia thea an evergreen plant contains antioxidants which prevent and repair cellular damage caused by reactive free radicals. Supervitamin drinks containing a combination of Hordeum vulgare, Medicago sativa and Spirulina enhances the activity of immune cells against cancer. Mentha species containing antioxidants prevent reocurrence of cancer.

  11. Heterocyclic chalcone analogues as potential anticancer agents.

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    Sharma, Vikas; Kumar, Vipin; Kumar, Pradeep

    2013-03-01

    Chalcones, aromatic ketones and enones acting as the precursor for flavonoids such as Quercetin, are known for their anticancer effects. Although, parent chalcones consist of two aromatic rings joined by a three-carbon α,β-unsaturated carbonyl system, various synthetic compounds possessing heterocyclic rings like pyrazole, indole etc. are well known and proved to be effective anticancer agents. In addition to their use as anticancer agents in cancer cell lines, heterocyclic analogues are reported to be effective even against resistant cell lines. In this connection, we hereby highlight the potential of various heterocyclic chalcone analogues as anticancer agents with a brief summary about therapeutic potential of chalcones, mechanism of anticancer action of various chalcone analogues, and current and future prospects related to the chalcones-derived anticancer research. Furthermore, some key points regarding chalcone analogues have been reviewed by analyzing their medicinal properties. PMID:22721390

  12. Novel anticancer agents from plant sources

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    Shah Unnati; Shah Ripal; Acharya Sanjeev; Acharya Niyati

    2013-01-01

    Plants remain an important source of new drugs,new drug leads and new chemical entities.Plant based drug discovery resulted mainly in the development of anticancer and anti-infectious agents,and continues to contribute to the new leads in clinical trials.Natural product drugs play a dominant role in pharmaceutical care.Several plant-derived compounds are currently successfully employed in cancer treatment.There are many classes of plant-derived cytotoxic natural products studied for further improvement and development of drugs.New anticancer drugs derived from research on plant antitumor agents will be continuously discovered.The basic aim of this review is to explore the potential of newly discovered anticancer compounds from medicinal plants,as a lead for anticancer drug development.It will be helpful to explore the medicinal value of plants and for new drug discovery from them for the researchers and scientists around the globe.

  13. Novel Anticancer Agents from Ascidiacea

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    Vervoort, Hélène C.

    1999-01-01

    This thesis presents an effort to contribute to the discovery and development of struc­turally and mechanistically novel anticancer drugs. In order to reach this goal it focusses on the biologically active secondary metabolites of marine invertebrates of the class As­cidiacea (phylum Chordata, subphylum Urochordata (Tunicata), class Ascidacea). Three distinct areas of research were combined. The first part concerns the discovery of two novel, naturally occurring didemnin depsipeptide...

  14. Some medicinal plants as natural anticancer agents

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    Govind Pandey

    2009-01-01

    Full Text Available India is the largest producer of medicinal plants and is rightly called the "Botanical garden of the World". The medicinal plants, besides having natural therapeutic values against various diseases, also provide high quality of food and raw materials for livelihood. Considerable works have been done on these plants to treat cancer, and some plant products have been marketed as anticancer drugs, based on the traditional uses and scientific reports. These plants may promote host resistance against infection by re-stabilizing body equilibrium and conditioning the body tissues. Several reports describe that the anticancer activity of medicinal plants is due to the presence of antioxidants in them. In fact, the medicinal plants are easily available, cheaper and possess no toxicity as compared to the modern (allopathic drugs. Hence, this review article contains 66 medicinal plants, which are the natural sources of anticancer agents.

  15. Reengineered tricyclic anti-cancer agents.

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    Kastrinsky, David B; Sangodkar, Jaya; Zaware, Nilesh; Izadmehr, Sudeh; Dhawan, Neil S; Narla, Goutham; Ohlmeyer, Michael

    2015-10-01

    The phenothiazine and dibenzazepine tricyclics are potent neurotropic drugs with a documented but underutilized anti-cancer side effect. Reengineering these agents (TFP, CPZ, CIP) by replacing the basic amine with a neutral polar functional group (e.g., RTC-1, RTC-2) abrogated their CNS effects as demonstrated by in vitro pharmacological assays and in vivo behavioral models. Further optimization generated several phenothiazines and dibenzazepines with improved anti-cancer potency, exemplified by RTC-5. This new lead demonstrated efficacy against a xenograft model of an EGFR driven cancer without the neurotropic effects exhibited by the parent molecules. Its effects were attributed to concomitant negative regulation of PI3K-AKT and RAS-ERK signaling. PMID:26372073

  16. Histone deacetylase inhibitors (HDACIs: multitargeted anticancer agents

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    Ververis K

    2013-02-01

    Full Text Available Katherine Ververis,1 Alison Hiong,1 Tom C Karagiannis,1,* Paul V Licciardi2,*1Epigenomic Medicine, Alfred Medical Research and Education Precinct, 2Allergy and Immune Disorders, Murdoch Childrens Research Institute, Melbourne, VIC, Australia*These authors contributed equally to this workAbstract: Histone deacetylase (HDAC inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb homeostasis, and contribute to neoplastic growth. The family of HDAC inhibitors is large and diverse. It includes a range of naturally occurring and synthetic compounds that differ in terms of structure, function, and specificity. HDAC inhibitors have multiple cell type-specific effects in vitro and in vivo, such as growth arrest, cell differentiation, and apoptosis in malignant cells. HDAC inhibitors have the potential to be used as monotherapies or in combination with other anticancer therapies. Currently, there are two HDAC inhibitors that have received approval from the US FDA for the treatment of cutaneous T-cell lymphoma: vorinostat (suberoylanilide hydroxamic acid, Zolinza and depsipeptide (romidepsin, Istodax. More recently, depsipeptide has also gained FDA approval for the treatment of peripheral T-cell lymphoma. Many more clinical trials assessing the effects of various HDAC inhibitors on hematological and solid malignancies are currently being conducted. Despite the proven anticancer effects of particular HDAC inhibitors against certain cancers, many aspects of HDAC enzymes and HDAC inhibitors are still not fully understood. Increasing our understanding of the effects of HDAC inhibitors, their targets and mechanisms of action will be critical for the

  17. Snake venom: a potent anticancer agent.

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    Jain, Deepika; Kumar, Sudhir

    2012-01-01

    Since cancer is one of the leading causes of death worldwide, and there is an urgent need to find better treatment. In recent years remarkable progress has been made towards the understanding of proposed hallmarks of cancer development and treatment. Treatment modalities comprise radiation therapy, surgery, chemotherapy, immunotherapy and hormonal therapy. Currently, the use of chemotherapeutics remains the predominant option for clinical control. However, one of the major problems with successful cancer therapy using chemotherapeutics is that patients often do not respond or eventually develop resistance after initial treatment. This has led to the increased use of anticancer drugs developed from natural resources. The biodiversity of venoms and toxins makes them a unique source from which novel therapeutics may be developed. In this review, the anticancer potential of snake venom is discussed. Some of the included molecules are under clinical trial and may find application for anticancer drug development in the near future. PMID:23244070

  18. Arene ruthenium complexes as anticancer agents

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    Süss-Fink, Georg

    2012-01-01

    Neutral or cationic arene ruthenium complexes providing both hydrophilic as well as hydrophobic properties due to the robustness of the ruthenium–arene unit hold a high potential for the development of metal-based anticancer drugs. Mononuclear arene ruthenium complexes containing P- or N-donor ligands or N,N-, N,O- or O,O-chelating ligands, dinuclear arene ruthenium systems with adjustable organic linkers, trinuclear arene ruthenium clusters containing an oxo cap, tetranuclear arene ruthenium...

  19. Some medicinal plants as natural anticancer agents

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    Govind Pandey; S Madhuri

    2009-01-01

    India is the largest producer of medicinal plants and is rightly called the "Botanical garden of the World". The medicinal plants, besides having natural therapeutic values against various diseases, also provide high quality of food and raw materials for livelihood. Considerable works have been done on these plants to treat cancer, and some plant products have been marketed as anticancer drugs, based on the traditional uses and scientific reports. These plants may promote host resistance agai...

  20. Natural compounds as anticancer agents: Experimental evidence

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    Wang, Jiao; Jiang, Yang-Fu

    2012-01-01

    Cancer prevention research has drawn much attention worldwide. It is believed that some types of cancer can be prevented by following a healthy life style. Cancer chemoprevention by either natural or synthetic agents is a promising route towards lowering cancer incidence. In recent years, the concept of cancer chemoprevention has evolved greatly. Experimental studies in animal models demonstrate that the reversal or suppression of premalignant lesions by chemopreventive agents is achievable. ...

  1. Pharmaceutical development of selected novel anticancer agents : from drugs substance to dosage form

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    Brok, M.W.J. (Monique Wilhelmina Johanna) den

    2004-01-01

    Despite the substantial progress made over the last decades in the treatment of cancer, there still is a great need for novel therapies. Especially for patients with advanced disease, chemotherapy is the best option. Nature is the primary source of anticancer drugs with compounds isolated from plants or micro-organisms. Moreover, the marine ecosystem provides for a growing number of promising agents in clinical trials. Besides natural resources, the increasing knowledge of tumour pathology an...

  2. BlueBerry Isolate, Pterostilbene, Functions as a Potential Anticancer Stem Cell Agent in Suppressing Irradiation-Mediated Enrichment of Hepatoma Stem Cells

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    Chi-Ming Lee

    2013-01-01

    Full Text Available For many malignancies, radiation therapy remains the second option only to surgery in terms of its curative potential. However, radiation-induced tumor cell death is limited by a number of factors, including the adverse response of the tumor microenvironment to the treatment and either intrinsic or acquired mechanisms of evasive resistance, and the existence of cancer stem cells (CSCs. In this study, we demonstrated that using different doses of irradiation led to the enrichment of CD133+ Mahlavu cells using flow cytometric method. Subsequently, CD133+ Mahlavu cells enriched by irradiation were characterized for their stemness gene expression, self-renewal, migration/invasion abilities, and radiation resistance. Having established irradiation-enriched CD133+ Mahlavu cells with CSC properties, we evaluated a phytochemical, pterostilbene (PT, found abundantly in blueberries, against irradiation-enriched CSCs. It was shown that PT treatment dose-dependently reduced the enrichment of CD133+ Mahlavu cells upon irradiation; PT treatment also prevented tumor sphere formation, reduced stemness gene expression, and suppressed invasion and migration abilities as well as increasing apoptosis of CD133+ Mahlavu CSCs. Based on our experimental data, pterostilbene could be used to prevent the enrichment of CD133+ hepatoma CSCs and should be considered for future clinical testing as a combined agent for HCC patients.

  3. Monitoring of occupational exposure to cytostatic anticancer agents.

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    Sorsa, M; Anderson, D

    1996-08-17

    Many anticancer agents have been shown to be carcinogenic, mutagenic and teratogenic in experimental animals and in in vitro test systems. Epidemiological data on the association of second neoplasms with a specific chemotherapy treatment is available on some 30 agents, and in the case of 10 compounds the overall evidence on human carcinogenicity has been evaluated to be conclusive (Group 1: IARC, 1987 and 1990). The primary source of human exposure to anticancer drugs is from their use in therapy of cancer. However, persons employed in the manufacture, preparation and administration of the drugs to patients and in nursing patients may also be exposed. Safe handling of anticancer drugs, since the introduction of various general handling guidelines, is now good practice in hospitals, pharmacies and drug manufacturing companies of most developed countries. Careless handling of cancer chemotherapeutic agents may lead to exposure of the personnel in amounts detectable with chemical or biological methods in the body fluids or cell samples of the subjects. The exposure is typically to mixed compounds over long-term and to low exposure levels with accidental peaks. Therefore, the use of biological exposure markers is appropriate for the monitoring of such exposure patterns. The biological markers/methods for exposure assessment are either non-specific (e.g., cytogenetic damage, point mutations or 32P-post-labelling adducts in peripheral blood lymphocytes, urinary mutagenicity) or specific for a given compound (immunological methods for DNA adducts, specific analytical methods). Studies have revealed minor amounts of cyclophosphamide in the urine of pharmacy technicians and nurses handling the drug even when taking special safety precautions (Sessink et al. (1994a) J. Occup. Med., 36, 79; Sessink et al. (1994b) Arch. Env. Health, 49, 165). Another study showed surface wipe samples with measurable cyclophosphamide even away from the handling site (McDevitt et al. (1993) J

  4. Anti-cancer natural products isolated from chinese medicinal herbs

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    Wu Guosheng

    2011-07-01

    Full Text Available Abstract In recent years, a number of natural products isolated from Chinese herbs have been found to inhibit proliferation, induce apoptosis, suppress angiogenesis, retard metastasis and enhance chemotherapy, exhibiting anti-cancer potential both in vitro and in vivo. This article summarizes recent advances in in vitro and in vivo research on the anti-cancer effects and related mechanisms of some promising natural products. These natural products are also reviewed for their therapeutic potentials, including flavonoids (gambogic acid, curcumin, wogonin and silibinin, alkaloids (berberine, terpenes (artemisinin, β-elemene, oridonin, triptolide, and ursolic acid, quinones (shikonin and emodin and saponins (ginsenoside Rg3, which are isolated from Chinese medicinal herbs. In particular, the discovery of the new use of artemisinin derivatives as excellent anti-cancer drugs is also reviewed.

  5. Anticancer activity studies of cubebin isolated from Piper cubeba and its synthetic derivatives.

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    Rajalekshmi, Dhanya S; Kabeer, Farha A; Madhusoodhanan, Arya R; Bahulayan, Arun K; Prathapan, Remani; Prakasan, Nisha; Varughese, Sunil; Nair, Mangalam S

    2016-04-01

    (-)-Cubebin, isolated from the seeds of Piper cubeba, and its five different types of derivatives (a total of 17), with varying functionalities, were tested for their in vitro anticancer activity against six human cancer cell lines (A549, K562, SiHa, KB, HCT116 and HT29) using MTT assay. Cubebin as well as its derivatives containing lactone and amide groups showed significant anticancer activity. In some of the tested cell lines, the amide derivatives showed higher activity. Morphological analysis indicated that these compounds act through apoptosis mediated pathway of cell death and we expect that these results will pave new paths in the development of novel anticancer agents by the derivatization of (-)-cubebin. PMID:26916436

  6. T-oligo as an anticancer agent in colorectal cancer

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    Wojdyla, Luke; Stone, Amanda L. [Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL (United States); Sethakorn, Nan [Department of Medicine, University of Chicago, Chicago, IL (United States); Uppada, Srijayaprakash B.; Devito, Joseph T. [Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL (United States); Bissonnette, Marc [Department of Medicine, University of Chicago, Chicago, IL (United States); Puri, Neelu, E-mail: neelupur@uic.edu [Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL (United States)

    2014-04-04

    Highlights: • T-oligo induces cell cycle arrest, senescence, apoptosis, and differentiation in CRC. • Treatment with T-oligo downregulates telomere-associated proteins. • T-oligo combined with an EGFR-TKI additively inhibits cellular proliferation. • T-oligo has potential as an effective therapeutic agent for CRC. - Abstract: In the United States, there will be an estimated 96,830 new cases of colorectal cancer (CRC) and 50,310 deaths in 2014. CRC is often detected at late stages of the disease, at which point there is no effective chemotherapy. Thus, there is an urgent need for effective novel therapies that have minimal effects on normal cells. T-oligo, an oligonucleotide homologous to the 3′-telomere overhang, induces potent DNA damage responses in multiple malignant cell types, however, its efficacy in CRC has not been studied. This is the first investigation demonstrating T-oligo-induced anticancer effects in two CRC cell lines, HT-29 and LoVo, which are highly resistant to conventional chemotherapies. In this investigation, we show that T-oligo may mediate its DNA damage responses through the p53/p73 pathway, thereby inhibiting cellular proliferation and inducing apoptosis or senescence. Additionally, upregulation of downstream DNA damage response proteins, including E2F1, p53 or p73, was observed. In LoVo cells, T-oligo induced senescence, decreased clonogenicity, and increased expression of senescence associated proteins p21, p27, and p53. In addition, downregulation of POT1 and TRF2, two components of the shelterin protein complex which protects telomeric ends, was observed. Moreover, we studied the antiproliferative effects of T-oligo in combination with an EGFR tyrosine kinase inhibitor, Gefitinib, which resulted in an additive inhibitory effect on cellular proliferation. Collectively, these data provide evidence that T-oligo alone, or in combination with other molecularly targeted therapies, has potential as an anti-cancer agent in CRC.

  7. Anticancer activity of streptochlorin, a novel antineoplastic agent, in cholangiocarcinoma

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    Kwak TW

    2015-04-01

    Full Text Available Tae Won Kwak,1,* Hee Jae Shin,2,* Young-Il Jeong,1 Myoung-Eun Han,3 Sae-Ock Oh,3 Hyun-Jung Kim,4 Do Hyung Kim,5 Dae Hwan Kang1 1Biomedical Research Institute, Pusan National University Hospital, Busan, 2Marine Natural Products Chemistry Laboratory, Korea Institute of Ocean Science and Technology, Ansan, 3Department of Anatomy, School of Medicine, Pusan National University, Gyeongnam, 4Genewel Co Ltd. Gyeonggi-do, 5School of Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea *These authors contributed equally to this work Background: The aim of this study is to investigate the anticancer activity of streptochlorin, a novel antineoplastic agent, in cholangiocarcinoma. Methods: The anticancer activity of streptochlorin was evaluated in vitro in various cholangiocarcinoma cell lines for apoptosis, proliferation, invasiveness, and expression of various protein levels. A liver metastasis model was prepared by splenic injection of HuCC-T1 cholangiocarcinoma cells using a BALB/c nude mouse model to study the systemic antimetastatic efficacy of streptochlorin 5 mg/kg at 8 weeks. The antitumor efficacy of subcutaneously injected streptochlorin was also assessed using a solid tumor xenograft model of SNU478 cells for 22 days in the BALB/c nude mouse. Results: Streptochlorin inhibited growth and secretion of vascular endothelial growth factor by cholangiocarcinoma cells in a dose-dependent manner and induced apoptosis in vitro. In addition, streptochlorin effectively inhibited invasion and migration of cholangiocarcinoma cells. Secretion of vascular endothelial growth factor and activity of matrix metalloproteinase-9 in cholangiocarcinoma cells were also suppressed by treatment with streptochlorin. Streptochlorin effectively regulated metastasis of HuCC-T1 cells in a mouse model of liver metastasis. In a tumor xenograft study using SNU478 cells, streptochlorin significantly inhibited tumor growth without changes in body weight

  8. Rosemary (Rosmarinus officinalis L.) Extract as a Potential Complementary Agent in Anticancer Therapy.

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    González-Vallinas, Margarita; Reglero, Guillermo; Ramírez de Molina, Ana

    2015-01-01

    Cancer remains an important cause of mortality nowadays and, therefore, new therapeutic approaches are still needed. Rosemary (Rosmarinus officinalis L.) has been reported to possess antitumor activities both in vitro and in animal studies. Some of these activities were attributed to its major components, such as carnosic acid, carnosol, ursolic acid, and rosmarinic acid. Initially, the antitumor effects of rosemary were attributed to its antioxidant activity. However, in recent years, a lack of correlation between antioxidant and antitumor effects exerted by rosemary was reported, and different molecular mechanisms were related to its tumor inhibitory properties. Moreover, supported by the U.S. Food and Drug Administration and the European Food and Safety Authority, specific compositions of rosemary extract were demonstrated to be safe for human health and used as antioxidant additive in foods, suggesting the potential easy application of this agent as a complementary approach in cancer therapy. In this review, we aim to summarize the reported anticancer effects of rosemary, the demonstrated molecular mechanisms related to these effects and the interactions between rosemary and currently used anticancer agents. The possibility of using rosemary extract as a complementary agent in cancer therapy in comparison with its isolated components is discussed. PMID:26452641

  9. Anticancer activity of flavane gallates isolated from Plicosepalus curviflorus

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    Ghada Ahmed Fawzy

    2014-01-01

    Full Text Available Background: Previous investigation of the methanol extract of Plicosepalus curviflorus leaves led to the isolation of two new flavane gallates (1, 2, together with other compounds including quercetin (3. The stems of P. curviflorus are used traditionally for the treatment of cancer in Yemen. Objective: The aim of this study was to evaluate the anticancer activity of the plant methanol extract as well as isolated compounds (1-3. Materials and Methods: The human cancer cell lines used were; MCF-7, HepG-2, HCT-116, Hep-2, HeLa and normal, Vero cell line using the Crystal Violet Staining method (CVS. Results: Quercetin (3 possessed the highest anticancer effect against all five cell lines (IC 50 ranging from 3.6 to 16.2 μg/ml. It was followed by 2S, 3R-3, 3′, 4′, 5, 7-pentahydroxyflavane-5-O-gallate (1 , with IC 50 ranging from 11.6 to 38.8 μg/ml. The weakest anticancer activity was given by 2S, 3R-3,3′,4′,5,5′,7-hexahydroxyflavane-3′,5-di-O-gallate (2 with IC 50 ranging from 39.8 to above 50 μg/ml, compared to vinblastine sulphate as reference drug. Colon, liver and breast cell lines seemed to be more sensitive to the tested compounds than the cervical and laryngeal cell lines. Concerning the cytotoxic effect on Vero cell line, the pentahydroxyflavane-5-O-gallate (1 showed the highest IC 50 ( 138.2 μg/ml, while quercetin exhibited the lowest IC 50 to Vero cells (30.5 μg/ml, compared to vinblastine sulphate as reference drug (IC 50: 39.7 μg/ml. Conclusion: The results suggest the possible use of compounds 1 and 3 as anticancer drugs especially against colon and liver cancers.

  10. Current developments of coumarin-based anti-cancer agents in medicinal chemistry.

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    Emami, Saeed; Dadashpour, Sakineh

    2015-09-18

    Cancer is one of the leading health hazards and the prominent cause of death in the world. A number of anticancer agents are currently in clinical practice and used for treatment of various kinds of cancers. There is no doubt that the existing arsenal of anticancer agents is insufficient due to the high incidence of side effects and multidrug resistance. In the efforts to develop suitable anticancer drugs, medicinal chemists have focused on coumarin derivatives. Coumarin is a naturally occurring compound and a versatile synthetic scaffold possessing wide spectrum of biological effects including potential anticancer activity. This review article covers the current developments of coumarin-based anticancer agents and also discusses the structure-activity relationship of the most potent compounds. PMID:26318068

  11. A Systematic Review of the Anticancer Properties of Compounds Isolated from Licorice (Gancao).

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    Tang, Zheng-Hai; Li, Ting; Tong, Yun-Guang; Chen, Xiao-Jia; Chen, Xiu-Ping; Wang, Yi-Tao; Lu, Jin-Jian

    2015-12-01

    Licorice (Gancao in Chinese) has been used worldwide as a botanical source in medicine and as a sweetening agent in food products for thousands of years. Triterpene saponins and flavonoids are its main ingredients that exhibit a variety of biological activities, including hepatoprotective, antiulcer, anti-inflammatory, antiviral and anticancer effects among others. This review attempts to summarize the current knowledge on the anticancer properties and mechanisms of the compounds isolated from licorice and obtain new insights for further research and development of licorice. A broad spectrum of in vitro and in vivo studies have recently demonstrated that the mixed extracts and purified compounds from licorice exhibit evident anticancer properties by inhibition of proliferation, induction of cell cycle arrest, apoptosis, autophagy, differentiation, suppression of metastasis, angiogenesis, and sensitization of chemotherapy or radiotherapy. A combined treatment of licorice compounds and clinical chemotherapy drugs remarkably enhances anticancer effects and reduces the side effects of chemotherapeutics. Furthermore, glycyrrhizic acid and glycyrrhetinic acid in licorice have been indicated to present obvious liver-targeting effects in targeted drug delivery systems for hepatocellular carcinoma treatment. PMID:26695708

  12. Triterpenoids of Marine Origin as Anti-Cancer Agents

    Directory of Open Access Journals (Sweden)

    Yong-Xin Li

    2013-07-01

    Full Text Available Triterpenoids are the most abundant secondary metabolites present in marine organisms, such as marine sponges, sea cucumbers, marine algae and marine-derived fungi. A large number of triterpenoids are known to exhibit cytotoxicity against a variety of tumor cells, as well as anticancer efficacy in preclinical animal models. In this review efforts have been taken to review the structural features and the potential use of triterpenoids of marine origin to be used in the pharmaceutical industry as potential anti-cancer drug leads.

  13. Synthesis and evaluation of flavanones as anticancer agents

    Directory of Open Access Journals (Sweden)

    Y Murti

    2014-01-01

    Full Text Available A few flavanones were synthesised by cyclisation of corresponding 3-(heteroaryl-1(2-hydroxyphenyl prop-2-en-1-one with sodium acetate in alcohol-water and evaluated for activity. Synthesised compounds were assayed for their in vitro anticancer activity against three human cancer cell lines, mammary adenocarcinoma (MCF7, human colon adenocarcinoma (HT29 and human kidney adenocarcinoma (A498 using sulforhodamine B dye. Results indicated that most of the compounds exhibited significant in vitro anticancer potential. Among them, compound having furan ring showed most potent activity against all the tested cell lines.

  14. Quinones derived from plant secondary metabolites as anti-cancer agents.

    Science.gov (United States)

    Lu, Jin-Jian; Bao, Jiao-Lin; Wu, Guo-Sheng; Xu, Wen-Shan; Huang, Ming-Qing; Chen, Xiu-Ping; Wang, Yi-Tao

    2013-03-01

    Quinones are plant-derived secondary metabolites that present some anti-proliferation and anti-metastasis effects in various cancer types both in vitro and in vivo. This review focuses on the anti-cancer prospects of plant-derived quinones, namely, aloe-emodin, juglone, β-lapachol, plumbagin, shikonin, and thymoquinone. We intend to summarize their anti-cancer effects and investigate the mechanism of actions to promote the research and development of anti-cancer agents from quinones. PMID:22931417

  15. Design and development of polynuclear ruthenium and platinum polypyridyl complexes in search of new anticancer agents

    OpenAIRE

    Schilden, Karlijn van der

    2006-01-01

    The research described in this Ph.D. Thesis has been devoted to the design and development of polynuclear polypyridyl ruthenium and ruthenium-platinum complexes in search of new anticancer agents. A variety of polynuclear ruthenium and ruthenium-platinum complexes has been synthesized with a long and flexible linker. The complexes are characterized and have been studied for anticancer activity. The ruthenium unit of the dinuclear complexes varies in molecular structure, which may result in di...

  16. ANTICANCER ACTIVITY OF ISOLATED CHEMICAL CONSTITUENTS FROM MILIUSA SMITHIAE

    Directory of Open Access Journals (Sweden)

    Chonthicha Naphong

    2013-01-01

    Full Text Available Miliusa plants belonging to the family Annonaceae are found in Thailand and have been used as Thai traditional medicines. There have been a few previously reports on the chemical constituents of plants in this genus, describing the presence of aporphine alkaloids, terpenoids, flavonoids, phenylpropanoids, styrylpyrones, bis-styryls and homogentisic acid derivatives. Miliusa smithiae, a new species for Thailand and world, has not been studied chemical composition. The present study described phytochemical study of the leaves and twigs of M. smithiae together with their cytotoxicity. The M. smithiae was selected and percolated with hexane, ethyl acetate, acetone and methanol. The extracts were purified and elucidated chemical structures. The constituent of ethyl acetate extract of M. smithiae has been investigated. We isolated and identified two flavonoid derivatives, 5-hydroxy-3,7,4′-trimetoxyflavone (1 and 5,3′-dihydroxy-3,7,4′-trimetoxyflavone (2. The structures of these compounds were elucidated on the basis of spectroscopic evidence. Studies on ethyl acetate extract of M. smithiae has now resulted the isolation and structural characterization of two flavonoids. Their anticancer activities were evaluated using SRB assays. In this method, compound 2 showed potential activity in cell lines.

  17. Cultivation and utility of Piptoporus betulinus fruiting bodies as a source of anticancer agents.

    Science.gov (United States)

    Pleszczyńska, Małgorzata; Wiater, Adrian; Siwulski, Marek; Lemieszek, Marta K; Kunaszewska, Justyna; Kaczor, Józef; Rzeski, Wojciech; Janusz, Grzegorz; Szczodrak, Janusz

    2016-09-01

    Piptoporus betulinus is a wood-rotting basidiomycete used in medicine and biotechnology. However, to date, no indoor method for cultivation of this mushroom fruiting bodies has been developed. Here we present the first report of successful production of P. betulinus mature fruiting bodies in artificial conditions. Four P. betulinus strains were isolated from natural habitats and their mycelia were inoculated into birch sawdust substrate supplemented with organic additives. All the strains effectively colonized the medium but only one of them produced fruiting bodies. Moisture and organic supplementation of the substrate significantly determined the fruiting process. The biological efficiency of the P. betulinus PB01 strain cultivated on optimal substrate (moisture and organic substance content of 55 and 65 and 25 or 35 %, respectively) ranged from 12 to 16 %. The mature fruiting bodies reached weight in the range from 50 to 120 g. Anticancer properties of water and ethanol extracts isolated from both cultured and nature-derived fruiting bodies of P. betulinus were examined in human colon adenocarcinoma, human lung carcinoma and human breast cancer cell lines. The studies revealed antiproliferative and antimigrative properties of all the investigated extracts. Nevertheless the most pronounced effects demonstrated the ethanol extracts, obtained from fruiting bodies of cultured P. betulinus. Summarizing, our studies proved that P. betulinus can be induced to fruit in indoor artificial culture and the cultured fruiting bodies can be used as a source of potential anticancer agents. In this respect, they are at least as valuable as those sourced from nature. PMID:27465851

  18. Potential role of garcinol as an anticancer agent.

    Science.gov (United States)

    Saadat, Nadia; Gupta, Smiti V

    2012-01-01

    Garcinol, a polyisoprenylated benzophenone, is extracted from the rind of the fruit of Garcinia indica, a plant found extensively in tropical regions. Although the fruit has been consumed traditionally over centuries, its biological activities, specifically its anticancer potential is a result of recent scientific investigations. The anticarcinogenic properties of garcinol appear to be moderated via its antioxidative, anti-inflammatory, antiangiogenic, and proapoptotic activities. In addition, garcinol displays effective epigenetic influence by inhibiting histone acetyltransferases (HAT 300) and by possible posttranscriptional modulation by mi RNA profiles involved in carcinogenesis. In vitro as well as some in vivo studies have shown the potential of this compound against several cancers types including breast, colon, pancreatic, and leukemia. Although this is a promising molecule in terms of its anticancer properties, investigations in relevant animal models, and subsequent human trials are warranted in order to fully appreciate and confirm its chemopreventative and/or therapeutic potential. PMID:22745638

  19. Discovery of Natural Product Anticancer Agents from Biodiverse Organisms

    OpenAIRE

    Kinghorn, A. Douglas; Chin, Young-Won; Swanson, Steven M.

    2009-01-01

    For over 40 years, small organic molecules derived naturally from microbes and plants have provided a number of useful cancer chemotherapeutic drugs. The search for naturally occurring lead compounds of this type has continued in recent years, with the constituents of marine fauna and flora as well as those of terrestrial microorganisms and plants being investigated for their anti-cancer activities. In the present short review, selected new compounds or their derivatives are described that ha...

  20. Triterpenoids of Marine Origin as Anti-Cancer Agents

    OpenAIRE

    Yong-Xin Li; Himaya, S.W.A.; Se-Kwon Kim

    2013-01-01

    Triterpenoids are the most abundant secondary metabolites present in marine organisms, such as marine sponges, sea cucumbers, marine algae and marine-derived fungi. A large number of triterpenoids are known to exhibit cytotoxicity against a variety of tumor cells, as well as anticancer efficacy in preclinical animal models. In this review efforts have been taken to review the structural features and the potential use of triterpenoids of marine origin to be used in the pharmaceutical industry ...

  1. Potential Role of Garcinol as an Anticancer Agent

    OpenAIRE

    Gupta, Smiti V.; Nadia Saadat

    2012-01-01

    Garcinol, a polyisoprenylated benzophenone, is extracted from the rind of the fruit of Garcinia indica, a plant found extensively in tropical regions. Although the fruit has been consumed traditionally over centuries, its biological activities, specifically its anticancer potential is a result of recent scientific investigations. The anticarcinogenic properties of garcinol appear to be moderated via its antioxidative, anti-inflammatory, antiangiogenic, and proapoptotic activities. In addition...

  2. Second annual progress report on introduction and use of investigational anticancer agents in Australia, 1984-1985. Anticancer Subcommittee of the Australian Drug Evaluation Committee.

    Science.gov (United States)

    1986-03-31

    Since the publication of its first report, the Anticancer Subcommittee of the Australian Drug Evaluation Committee (ADEC) has provided advice to ADEC and to the Commonwealth Department of Health on investigational anticancer agents in all stages of development. This second report outlines the progress in 1984-1985. PMID:3515139

  3. Selective anti-cancer agents as anti-aging drugs

    OpenAIRE

    Blagosklonny, Mikhail V.

    2013-01-01

    Recent groundbreaking discoveries have revealed that IGF-1, Ras, MEK, AMPK, TSC1/2, FOXO, PI3K, mTOR, S6K, and NFκB are involved in the aging process. This is remarkable because the same signaling molecules, oncoproteins and tumor suppressors, are well-known targets for cancer therapy. Furthermore, anti-cancer drugs aimed at some of these targets have been already developed. This arsenal could be potentially employed for anti-aging interventions (given that similar signaling molecules are inv...

  4. Design and synthesis of harzialactone analogues: promising anticancer agents.

    Science.gov (United States)

    Pawar, Vishwas U; Ghosh, Sougata; Chopade, Balu A; Shinde, Vaishali S

    2010-12-15

    New homologues of harzialactone were synthesized using D-glucose as chiral template. Wittig reaction to introduce aromatic moiety in 10 and chemoselective anomeric oxidation of 13 were used as key reactions in our synthesis. Anticancer activity of these target molecules was assessed against five cancer cell lines, P388D1, HL60, COLO-205, Zr-75-1 and HeLa. Both compound 5 and 6, showed significant activity against colon cancer (COLO-205) and cervical cancer (HeLa) and moderate with others. To the best of our knowledge, this is the first report of harzialactone analogues as potent inhibitors of human colon and cervical cancer. PMID:21074431

  5. New water soluble pyrroloquinoline derivatives as new potential anticancer agents.

    Science.gov (United States)

    Ferlin, Maria Grazia; Marzano, Christine; Dalla Via, Lisa; Chilin, Adriana; Zagotto, Giuseppe; Guiotto, Adriano; Moro, Stefano

    2005-08-01

    A new class of water soluble 3H-pyrrolo[3,2-f]quinoline derivatives has been synthesized and investigated as potential anticancer drugs. Water solubility profiles have been used to select the most promising derivatives. The novel compound 10, having two (2-diethylamino-ethyl) side chains linked through positions 3N and 9O, presents a suitable water solubility profile, and it was shown to exhibit cell growth inhibitory properties when tested against the in-house panel of cell lines, in particular those obtained from melanoma. PMID:15936202

  6. (-)-Arctigenin as a lead compound for anticancer agent.

    Science.gov (United States)

    Chen, Gui-Rong; Li, Hong-Fu; Dou, De-Qiang; Xu, Yu-Bin; Jiang, Hong-Shuai; Li, Fu-Rui; Kang, Ting-Guo

    2013-01-01

    (-)-Arctigenin, an important active constituent of the traditional Chinese herb Fructus Arctii, was found to exhibit various bioactivities, so it can be used as a good lead compound for further structure modification in order to find a safer and more potent medicine. (-)-Arctigenin derivatives 1-5 of (-)-arctingen were obtained by modifying with ammonolysis at the lactone ring and sulphonylation at C (6') and C (6″) and O-demethylation at CH3O-C (3'), CH3O-C (3″) and CH3O-C (4″), and their anticancer bioactivities were examined. PMID:23962054

  7. Anticancer and Antitumor Potential of Fucoidan and Fucoxanthin, Two Main Metabolites Isolated from Brown Algae

    Directory of Open Access Journals (Sweden)

    Soheil Zorofchian Moghadamtousi

    2014-01-01

    Full Text Available Seaweed is one of the largest producers of biomass in marine environment and is a rich arsenal of active metabolites and functional ingredients with valuable beneficial health effects. Being a staple part of Asian cuisine, investigations on the crude extracts of Phaeophyceae or brown algae revealed marked antitumor activity, eliciting a variety of research to determine the active ingredients involved in this potential. The sulfated polysaccharide of fucoidan and carotenoid of fucoxanthin were found to be the most important active metabolites of brown algae as potential chemotherapeutic or chemopreventive agents. This review strives to provide detailed account of all current knowledge on the anticancer and antitumor activity of fucoidan and fucoxanthin as the two major metabolites isolated from brown algae.

  8. Phytochemicals and Biogenic Metallic Nanoparticles as Anticancer Agents.

    Science.gov (United States)

    Rao, Pasupuleti Visweswara; Nallappan, Devi; Madhavi, Kondeti; Rahman, Shafiqur; Jun Wei, Lim; Gan, Siew Hua

    2016-01-01

    Cancer is a leading cause of death worldwide. Several classes of drugs are available to treat different types of cancer. Currently, researchers are paying significant attention to the development of drugs at the nanoscale level to increase their target specificity and to reduce their concentrations. Nanotechnology is a promising and growing field with multiple subdisciplines, such as nanostructures, nanomaterials, and nanoparticles. These materials have gained prominence in science due to their size, shape, and potential efficacy. Nanomedicine is an important field involving the use of various types of nanoparticles to treat cancer and cancerous cells. Synthesis of nanoparticles targeting biological pathways has become tremendously prominent due to the higher efficacy and fewer side effects of nanodrugs compared to other commercial cancer drugs. In this review, different medicinal plants and their active compounds, as well as green-synthesized metallic nanoparticles from medicinal plants, are discussed in relation to their anticancer activities. PMID:27057273

  9. Phytochemicals and Biogenic Metallic Nanoparticles as Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Pasupuleti Visweswara Rao

    2016-01-01

    Full Text Available Cancer is a leading cause of death worldwide. Several classes of drugs are available to treat different types of cancer. Currently, researchers are paying significant attention to the development of drugs at the nanoscale level to increase their target specificity and to reduce their concentrations. Nanotechnology is a promising and growing field with multiple subdisciplines, such as nanostructures, nanomaterials, and nanoparticles. These materials have gained prominence in science due to their size, shape, and potential efficacy. Nanomedicine is an important field involving the use of various types of nanoparticles to treat cancer and cancerous cells. Synthesis of nanoparticles targeting biological pathways has become tremendously prominent due to the higher efficacy and fewer side effects of nanodrugs compared to other commercial cancer drugs. In this review, different medicinal plants and their active compounds, as well as green-synthesized metallic nanoparticles from medicinal plants, are discussed in relation to their anticancer activities.

  10. Chrysin-piperazine conjugates as antioxidant and anticancer agents.

    Science.gov (United States)

    Patel, Rahul V; Mistry, Bhupendra; Syed, Riyaz; Rathi, Anuj K; Lee, Yoo-Jung; Sung, Jung-Suk; Shinf, Han-Seung; Keum, Young-Soo

    2016-06-10

    Synthesis of 7-(4-bromobutoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one intermediate treating chrysin with 1,4-dibromobutane facilitated combination of chrysin with a wide range of piperazine moieties which were equipped via reacting the corresponding amines with bis(2-chloroethyl)amine hydrochloride in diethylene glycol monomethyl ether solvent. Free radical scavenging potential of prepared products was analyzed in vitro adopting DPPH and ABTS bioassay in addition to the evaluation of in vitro anticancer efficacies against cervical cancer cell lines (HeLa and CaSki) and an ovarian cancer cell line SK-OV-3 using SRB assay. Bearable toxicity of 7a-w was examined employing Madin-Darby canine kidney (MDCK) cell line. In addition, cytotoxic nature of the presented compounds was inspected utilizing Human bone marrow derived mesenchymal stem cells (hBM-MSCs). Overall, 7a-w indicated remarkable antioxidant power in scavenging DPPH(·) and ABTS(·+), particularly analogs 7f, 7j, 7k, 7l, 7n, 7q, 7v, 7w have shown promising free radical scavenging activity. Analogs 7j and 7o are identified to be highly active candidates against HeLa and CaSki cell lines, whereas 7h and 7l along with 7j proved to be very sensitive towards ovarian cancer cell line SKOV-3. None of the newly prepared scaffolds showed cytotoxic nature toward hBM-MSCs cells. From the structure-activity point of view, nature and position of the electron withdrawing and electron donating functional groups on the piperazine core may contribute to the anticipated antioxidant and anticancer action. Different spectroscopic techniques (FT-IR, (1)H NMR, (13)C NMR, Mass) and elemental analysis (CHN) were utilized to confirm the desired structure of final compounds. PMID:26924226

  11. Design and development of polynuclear ruthenium and platinum polypyridyl complexes in search of new anticancer agents

    NARCIS (Netherlands)

    Schilden, Karlijn van der

    2006-01-01

    The research described in this Ph.D. Thesis has been devoted to the design and development of polynuclear polypyridyl ruthenium and ruthenium-platinum complexes in search of new anticancer agents. A variety of polynuclear ruthenium and ruthenium-platinum complexes has been synthesized with a long an

  12. Pharmaceutical development of the novel metal-based anticancer agents NAMI-A and AP 5280

    NARCIS (Netherlands)

    Bouma, M. (Marjan)

    2003-01-01

    The pharmaceutical development of the two novel metal-based anticancer agents NAMI-A and AP 5280 is described in this thesis, starting with the development of analytical methods for the quality control of drug substance and final product, via the formulation process leading to a stable, intravenous

  13. Targeted Anticancer Immunotoxins and Cytotoxic Agents with Direct Killing Moieties

    Directory of Open Access Journals (Sweden)

    Koji Kawakami

    2006-01-01

    Full Text Available Despite the progress of the bioinformatics approach to characterize cell-surface antigens and receptors on tumor cells, it remains difficult to generate novel cancer vaccines or neutralizing monoclonal antibody therapeutics. Among targeted cancer therapeutics, biologicals with targetable antibodies or ligands conjugated or fused to toxins or chemicals for direct cell-killing ability have been developed over the last 2 decades. These conjugated or fused chimeric proteins are termed immunotoxins or cytotoxic agents. Two agents, DAB389IL-2 (ONTAKTM targeting the interleukin-2 receptor and CD33-calicheamicin (Mylotarg®, have been approved by the FDA for cutaneous T-cell lymphoma (CTCL and relapsed acute myeloid leukemia (AML, respectively. Such targetable agents, including RFB4(dsFv-PE38 (BL22, IL13-PE38QQR, and Tf-CRM107, are being tested in clinical trials. Several agents using unique technology such as a cleavable adapter or immunoliposomes with antibodies are also in the preclinical stage. This review summarizes the generation, mechanism, and development of these agents. In addition, possible future directions of this therapeutic approach are discussed.

  14. Strategies to Optimize Molecularly Targeted Anti-Cancer Agent Combinations

    Directory of Open Access Journals (Sweden)

    Ayse Erdogan

    2015-12-01

    Full Text Available Cytotoxic agents which are used in cancer chemotherapy reduced several times the number of neoplastic cells but not fully. Therefore, usage of and ldquo;targeted therapeutics" which were developed with much more rational approach is increasing markedly in patients with solid cancer. Targeted therapeutics due to selective targets aims cancer cells with specific molecular defect thereby, kils the cancer cells, which makes it possible to continue normal cells in a healthy environment. The rapid emergence of hundreds of new agents that modulates ever-growing list of the cancer-specific molecular targets promise great hope for cancer patients. Evaluation of the target agent individually, in combination with standard therapy and other target agents bring about important development challenges. As possible combinations of drugs number is unlimited, the identification of the most promising combinations and giving priority to assessing their strategies are very important.In this article important elements of the development strategy of the target agent combinations will be considered. Difficulties in this kind of combinations of rational pre-clinical and clinical evaluation and possible approaches to overcome these challenges will be discussed. [Archives Medical Review Journal 2015; 24(4.000: 432-451

  15. Prolonging the exposure to anti-cancer agents

    NARCIS (Netherlands)

    O. Soepenberg (Otto)

    2004-01-01

    textabstractThis thesis includes phase I clinical and pharmacological studies on second and third generation topoisomerase I inhibitors, either administered orally, or intravenously as a macromolecular drug-delivery system, and on the antimicrotubulin agent, paclitaxel encapsulated in liposomes, to

  16. Double layered hydroxides as potential anti-cancer drug delivery agents.

    Science.gov (United States)

    Riaz, Ufana; Ashraf, S M

    2013-04-01

    The emergence of nanotechnology has changed the scenario of the medical world by revolutionizing the diagnosis, monitoring and treatment of cancer. This nanotechnology has been proved miraculous in detecting cancer cells, delivering chemotherapeutic agents and monitoring treatment from non-specific to highly targeted killing of tumor cells. In the past few decades, a number of inorganic materials have been investigated such as calcium phosphate, gold, carbon materials, silicon oxide, iron oxide, and layered double hydroxide (LDH) for examining their efficacy in targeting drug delivery. The reason behind the selection of these inorganic materials was their versatile and unique features efficient in drug delivery, such as wide availability, rich surface functionality, good biocompatibility, potential for target delivery, and controlled release of the drug from these inorganic nanomaterials. Although, the drug-LDH hybrids are found to be quite instrumental because of their application as advanced anti-cancer drug delivery systems, there has not been much research on them. This mini review is set to highlight the advancement made in the use of layered double hydroxides (LDHs) as anti-cancer drug delivery agents. Along with the advantages of LDHs as anti-cancer drug delivery agents, the process of interaction of some of the common anti-cancer drugs with LDH has also been discussed. PMID:23170959

  17. Bacterial biosynthesis and maturation of the didemnin anticancer agents

    OpenAIRE

    Xu, Ying; Kersten, Roland D.; Nam, Sang-Jip; Lu, Liang; Al-Suwailem, Abdulaziz M.; Zheng, Huajun; Fenical, William; Dorrestein, Pieter C.; Moore, Bradley S.; Qian, Pei-Yuan

    2012-01-01

    The antineoplastic agent didemnin B from the Caribbean tunicate Trididemnum solidum was the first marine drug to be clinically tested in humans. Because of its limited supply and its complex cyclic depsipeptide structure, considerable challenges were encountered during didemnin B's development that continue to limit aplidine (dehydrodidemnin B), which is currently being evaluated in numerous clinical trials. Herein we show that the didemnins are bacterial products produced by the marine α-pro...

  18. Repurposing the Clinically Efficacious Antifungal Agent Itraconazole as an Anticancer Chemotherapeutic.

    Science.gov (United States)

    Pace, Jennifer R; DeBerardinis, Albert M; Sail, Vibhavari; Tacheva-Grigorova, Silvia K; Chan, Kelly A; Tran, Raymond; Raccuia, Daniel S; Wechsler-Reya, Robert J; Hadden, M Kyle

    2016-04-28

    Itraconazole (ITZ) is an FDA-approved member of the triazole class of antifungal agents. Two recent drug repurposing screens identified ITZ as a promising anticancer chemotherapeutic that inhibits both the angiogenesis and hedgehog (Hh) signaling pathways. We have synthesized and evaluated first- and second-generation ITZ analogues for their anti-Hh and antiangiogenic activities to probe more fully the structural requirements for these anticancer properties. Our overall results suggest that the triazole functionality is required for ITZ-mediated inhibition of angiogenesis but that it is not essential for inhibition of Hh signaling. The synthesis and evaluation of stereochemically defined des-triazole ITZ analogues also provides key information as to the optimal configuration around the dioxolane ring of the ITZ scaffold. Finally, the results from our studies suggest that two distinct cellular mechanisms of action govern the anticancer properties of the ITZ scaffold. PMID:27014922

  19. Discovery of new anticancer agents from higher plants

    OpenAIRE

    Pan, Li; Chai, Hee-Byung; Kinghorn, A. Douglas

    2012-01-01

    Small organic molecules derived from higher plants have been one of the mainstays of cancer chemotherapy for approximately the past half a century. In the present review, selected single chemical entity natural products of plant origin and their semi-synthetic derivatives currently in clinical trials are featured as examples of new cancer chemotherapeutic drug candidates. Several more recently isolated compounds obtained from plants showing promising in vivo biological activity are also discu...

  20. 3D QSAR Analysis on Oxadiazole Derivatives as Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Sanmati K. Jain

    2011-07-01

    Full Text Available Three dimensional quantitative structure activity relationship (3D QSAR study by means of partial least square regression (PLSR method was performed on a series of 3-(Aryl-N-(Aryl-1, 2, 4-Oxadiazol-5-amines as antiproliferative agents using molecular design suite (VLifeMDS. This study was performed with 20 compounds (data set using sphere exclusion (SE algorithm and manual selection method used for the division of the data set into training and test set. PLSR methodology with stepwise (SW forward-backward variable selection method was used for building the QSAR models. Five predictive models were generated with sphere exclusion and two with manual data selection methods using PLSR. The most significant model is having correlation coefficient 0.9334 (squared correlation coefficient r2 = 0.8713 indicating noteworthy correlation between biological activity and descriptors. The model has internal predictivity 74.45% (q2 = 0.7445 and highest external predictivity 81.09 % (pred_r2 = 0.8109 and lowest error term for predictive correlation coefficient (pred_r2se = 0.1321. Model showed that steric (S_1278, S_751 and electrostatic (E_307 interactions play important role in determining antiproliferative activity. The molecular field analysis (MFA contour plots provided further understanding of the relationship between structural features of substituted oxadiazole derivatives and their activities which should be applicable to design newer potential antiproliferative agents.

  1. Can Some Marine-Derived Fungal Metabolites Become Actual Anticancer Agents?

    Science.gov (United States)

    Gomes, Nelson G M; Lefranc, Florence; Kijjoa, Anake; Kiss, Robert

    2015-06-01

    Marine fungi are known to produce structurally unique secondary metabolites, and more than 1000 marine fungal-derived metabolites have already been reported. Despite the absence of marine fungal-derived metabolites in the current clinical pipeline, dozens of them have been classified as potential chemotherapy candidates because of their anticancer activity. Over the last decade, several comprehensive reviews have covered the potential anticancer activity of marine fungal-derived metabolites. However, these reviews consider the term "cytotoxicity" to be synonymous with "anticancer agent", which is not actually true. Indeed, a cytotoxic compound is by definition a poisonous compound. To become a potential anticancer agent, a cytotoxic compound must at least display (i) selectivity between normal and cancer cells (ii) activity against multidrug-resistant (MDR) cancer cells; and (iii) a preferentially non-apoptotic cell death mechanism, as it is now well known that a high proportion of cancer cells that resist chemotherapy are in fact apoptosis-resistant cancer cells against which pro-apoptotic drugs have more than limited efficacy. The present review thus focuses on the cytotoxic marine fungal-derived metabolites whose ability to kill cancer cells has been reported in the literature. Particular attention is paid to the compounds that kill cancer cells through non-apoptotic cell death mechanisms. PMID:26090846

  2. Hormetic Effect of Berberine Attenuates the Anticancer Activity of Chemotherapeutic Agents.

    Directory of Open Access Journals (Sweden)

    Jiaolin Bao

    Full Text Available Hormesis is a phenomenon of biphasic dose response characterized by exhibiting stimulatory or beneficial effects at low doses and inhibitory or toxic effects at high doses. Increasing numbers of chemicals of various types have been shown to induce apparent hormetic effect on cancer cells. However, the underlying significance and mechanisms remain to be elucidated. Berberine, one of the major active components of Rhizoma coptidis, has been manifested with notable anticancer activities. This study aims to investigate the hormetic effect of berberine and its influence on the anticancer activities of chemotherapeutic agents. Our results demonstrated that berberine at low dose range (1.25 ~ 5 μM promoted cell proliferation to 112% ~170% of the untreated control in various cancer cells, while berberine at high dose rage (10 ~ 80 μM inhibited cell proliferation. Further, we observed that co-treatment with low dose berberine could significantly attenuate the anticancer activity of chemotherapeutic agents, including fluorouracil (5-FU, camptothecin (CPT, and paclitaxel (TAX. The hormetic effect and thereby the attenuated anticancer activity of chemotherapeutic drugs by berberine may attributable to the activated protective stress response in cancer cells triggered by berberine, as evidenced by up-regulated MAPK/ERK1/2 and PI3K/AKT signaling pathways. These results provided important information to understand the potential side effects of hormesis, and suggested cautious application of natural compounds and relevant herbs in adjuvant treatment of cancer.

  3. Discovery and development of natural product oridonin-inspired anticancer agents.

    Science.gov (United States)

    Ding, Ye; Ding, Chunyong; Ye, Na; Liu, Zhiqing; Wold, Eric A; Chen, Haiying; Wild, Christopher; Shen, Qiang; Zhou, Jia

    2016-10-21

    Natural products have historically been, and continue to be, an invaluable source for the discovery of various therapeutic agents. Oridonin, a natural diterpenoid widely applied in traditional Chinese medicines, exhibits a broad range of biological effects including anticancer and anti-inflammatory activities. To further improve its potency, aqueous solubility and bioavailability, the oridonin template serves as an exciting platform for drug discovery to yield better candidates with unique targets and enhanced drug properties. A number of oridonin derivatives (e.g. HAO472) have been designed and synthesized, and have contributed to substantial progress in the identification of new agents and relevant molecular mechanistic studies toward the treatment of human cancers and other diseases. This review summarizes the recent advances in medicinal chemistry on the explorations of novel oridonin analogues as potential anticancer therapeutics, and provides a detailed discussion of future directions for the development and progression of this class of molecules into the clinic. PMID:27344488

  4. Adding pharmacogenomics to the development of new marine-derived anticancer agents

    Directory of Open Access Journals (Sweden)

    Aracil Miguel

    2006-01-01

    Full Text Available Abstract Nature has always been a highly productive tool in the development of anticancer therapies. Renewed interest in the potential of this tool has recently been sparked by the realization that the marine ecosystem can be used for the discovery and development of new compounds with clinical potential in advanced resistant tumors. These compounds can be incorporated into combination approaches in a chronic therapy scenario. Our marine anticancer program is using the sea to develop new agents with activity in resistant solid tumors and to identify new cellular targets for therapeutic intervention. This review describes the integration of different pharmacogenomic tools in the development of Yondelis™, Aplidin® and Kahalalide F, three marine-derived compounds currently in Phase II or III development. Our results are reinforcing the targeted selectivity of these agents and opening the gates for customized therapies in cancer patients in the near future.

  5. Evaluation of Degradation Properties of Polyglycolide and Its Potential as Delivery Vehicle for Anticancer Agents

    International Nuclear Information System (INIS)

    Biodegradable polymers offer a unique combination of properties that can be tailored to suit nearly any controlled drug delivery application. The most common biodegradable polymers used for biomedical applications are semicrystalline polyesters and polyethers which possess good mechanical properties and have been used in many controlled release applications. Drug release from these polymers may be controlled by several mechanisms and these include diffusion of drug through a matrix, dissolution of polymer matrix and degradation of the polymer. This study aims to investigate the degradation and drug release properties of polyglycolide (1.03 dL/g), in which, cis platin, an anticancer agent was used as the model drug. The degradation behaviour of the chosen polymer is thought to largely govern the release of the anticancer agent in vitro.

  6. Caffeine-hydrazones as anticancer agents with pronounced selectivity toward T-lymphoblastic leukaemia cells

    Czech Academy of Sciences Publication Activity Database

    Kaplánek, R.; Jakubek, M.; Rak, J.; Kejik, Z.; Havlík, M.; Dolenský, B.; Frydrych, I.; Hajduch, M.; Kolář, M.; Bogdanová, K.; Králová, Jarmila; Dzubak, P.; Král, V.

    2015-01-01

    Roč. 60, Jun (2015), s. 19-29. ISSN 0045-2068 Grant ostatní: GA MŠk(CZ) EE2.3.30.0060; GA MŠk CZ.1.07/2.3.00/30.0041; GA MŠk(CZ) LO1304 Institutional support: RVO:68378050 Keywords : Anticancer agents * Cancer treatment * Caffeine-hydrazones * Leukaemia * Selectivity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.152, year: 2014

  7. Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer agents

    OpenAIRE

    Dinarvand, Rasoul

    2011-01-01

    R Dinarvand1,2, N Sepehri1, S Manoochehri1, H Rouhani1, F Atyabi1,21Department of Pharmaceutics, Faculty of Pharmacy, 2Nanotechnology Research Centre, Tehran University of Medical Sciences, Tehran, IranAbstract: The effectiveness of anticancer agents may be hindered by low solubility in water, poor permeability, and high efflux from cells. Nanomaterials have been used to enable drug delivery with lower toxicity to healthy cells and enhanced drug delivery to tumor cells. Different nanoparticle...

  8. Theobroma cacao: Review of the Extraction, Isolation, and Bioassay of Its Potential Anti-cancer Compounds.

    Science.gov (United States)

    Baharum, Zainal; Akim, Abdah Md; Hin, Taufiq Yap Yun; Hamid, Roslida Abdul; Kasran, Rosmin

    2016-02-01

    Plants have been a good source of therapeutic agents for thousands of years; an impressive number of modern drugs used for treating human diseases are derived from natural sources. The Theobroma cacao tree, or cocoa, has recently garnered increasing attention and become the subject of research due to its antioxidant properties, which are related to potential anti-cancer effects. In the past few years, identifying and developing active compounds or extracts from the cocoa bean that might exert anti-cancer effects have become an important area of health- and biomedicine-related research. This review provides an updated overview of T. cacao in terms of its potential anti-cancer compounds and their extraction, in vitro bioassay, purification, and identification. This article also discusses the advantages and disadvantages of the techniques described and reviews the processes for future perspectives of analytical methods from the viewpoint of anti-cancer compound discovery. PMID:27019680

  9. Spectral and electrochemical detection of protonated triplex formation by a small-molecule anticancer agent

    Science.gov (United States)

    Feng, Lingyan; Li, Xi; Peng, Yinghua; Geng, Jie; Ren, Jinsong; Qu, Xiaogang

    2009-10-01

    Triplex helical formation has been the focus of considerable interest because of possible applications in developing new molecular biology tools as well as therapeutic agents and the possible relevance of H-DNA structures in biology system. We report here that a small-molecule anticancer agent, coralyne, has binding preference to the less stable protonated triplex d(C +-T) 6:d(A-G) 6·d(C-T) 6 over duplex d(A-G) 6·d(C-T) 6 and shows different spectral and electrochemical characteristics when binding to triplex and duplex DNA, indicating that electrochemical technique can detect the less stable protonated triplex formation.

  10. Medical applications of nanoparticles in biological imaging, cell labeling, antimicrobial agents, and anticancer nanodrugs.

    Science.gov (United States)

    Singh, Ravina; Nalwa, Hari Singh

    2011-08-01

    This article reviews the applications of nanotechnology in the fields of medical and life sciences. Nanoparticles have shown promising applications from diagnosis to treatment of various types of diseases including cancer. In this review, we discuss the applications of nanostructured materials such as nanoparticles, quantum dots, nanorods, nanowires, and carbon nanotubes in diagnostics, biomarkers, cell labeling, contrast agents for biological imaging, antimicrobial agents, drug delivery systems, and anticancer nanodrugs for treatment of cancer and other infectious diseases. The adverse affects of nanoparticles on human skin from daily use in cosmetics and general toxicology of nanoscale materials are also reviewed. PMID:21870454

  11. New 1,4-anthracene-9,10-dione derivatives as potential anticancer agents.

    Science.gov (United States)

    Zagotto, G; Supino, R; Favini, E; Moro, S; Palumbo, M

    2000-01-01

    The amino-substituted anthracene-9,10-dione (9,10-anthraquinone) derivatives represent one of the most important classes of potential anticancer agents. To better understand the basic rules governing DNA sequence specificity, we have recently synthesized a new class of D- and L-aminoacyl-anthraquinone derivatives. We have tested these new compounds as cytotoxic agents, and we have correlated their activity with the configuration of the chiral aminoacyl moiety. Molecular modeling studies have been performed to compare the test drugs in terms of steric overlapping. PMID:10755224

  12. [Quod medicina aliis, aliis est acre venenum**--venoms as a source of anticancer agents].

    Science.gov (United States)

    Kucińska, Małgorzata; Ruciński, Piotr; Murias, Marek

    2013-01-01

    Natural product derived from plants and animals were used in folk medicine for centuries. The venoms produced by animals for hunting of self-defence are rich in bioactive compounds with broad spectrum of biological activity. The papers presents the most promising compounds isolated from venoms of snakes, scorpions and toads. For these compounds both: mechanism of anticancer activity as well as possibilities of clinical use are presented. PMID:24466712

  13. Can Some Marine-Derived Fungal Metabolites Become Actual Anticancer Agents?

    Directory of Open Access Journals (Sweden)

    Nelson G. M. Gomes

    2015-06-01

    Full Text Available Marine fungi are known to produce structurally unique secondary metabolites, and more than 1000 marine fungal-derived metabolites have already been reported. Despite the absence of marine fungal-derived metabolites in the current clinical pipeline, dozens of them have been classified as potential chemotherapy candidates because of their anticancer activity. Over the last decade, several comprehensive reviews have covered the potential anticancer activity of marine fungal-derived metabolites. However, these reviews consider the term “cytotoxicity” to be synonymous with “anticancer agent”, which is not actually true. Indeed, a cytotoxic compound is by definition a poisonous compound. To become a potential anticancer agent, a cytotoxic compound must at least display (i selectivity between normal and cancer cells (ii activity against multidrug-resistant (MDR cancer cells; and (iii a preferentially non-apoptotic cell death mechanism, as it is now well known that a high proportion of cancer cells that resist chemotherapy are in fact apoptosis-resistant cancer cells against which pro-apoptotic drugs have more than limited efficacy. The present review thus focuses on the cytotoxic marine fungal-derived metabolites whose ability to kill cancer cells has been reported in the literature. Particular attention is paid to the compounds that kill cancer cells through non-apoptotic cell death mechanisms.

  14. Essential Oils and Their Constituents as Anticancer Agents: A Mechanistic View

    Directory of Open Access Journals (Sweden)

    Nandini Gautam

    2014-01-01

    Full Text Available Exploring natural plant products as an option to find new chemical entities as anticancer agents is one of the fastest growing areas of research. Recently, in the last decade, essential oils (EOs have been under study for their use in cancer therapy and the present review is an attempt to collect and document the available studies indicating EOs and their constituents as anticancer agents. This review enlists nearly 130 studies of EOs from various plant species and their constituents that have been studied so far for their anticancer potential and these studies have been classified as in vitro and in vivo studies for EOs and their constituents. This review also highlights in-depth various mechanisms of action of different EOs and their constituents reported in the treatment strategies for different types of cancer. The current review indicates that EOs and their constituents act by multiple pathways and mechanisms involving apoptosis, cell cycle arrest, antimetastatic and antiangiogenic, increased levels of reactive oxygen and nitrogen species (ROS/RNS, DNA repair modulation, and others to demonstrate their antiproliferative activity in the cancer cell. The effect of EOs and their constituents on tumour suppressor proteins (p53 and Akt, transcription factors (NF-κB and AP-1, MAPK-pathway, and detoxification enzymes like SOD, catalase, glutathione peroxidase, and glutathione reductase has also been discussed.

  15. Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer agents

    Directory of Open Access Journals (Sweden)

    Rouhani H

    2011-04-01

    Full Text Available R Dinarvand1,2, N Sepehri1, S Manoochehri1, H Rouhani1, F Atyabi1,21Department of Pharmaceutics, Faculty of Pharmacy, 2Nanotechnology Research Centre, Tehran University of Medical Sciences, Tehran, IranAbstract: The effectiveness of anticancer agents may be hindered by low solubility in water, poor permeability, and high efflux from cells. Nanomaterials have been used to enable drug delivery with lower toxicity to healthy cells and enhanced drug delivery to tumor cells. Different nanoparticles have been developed using different polymers with or without surface modification to target tumor cells both passively and/or actively. Polylactide-co-glycolide (PLGA, a biodegradable polyester approved for human use, has been used extensively. Here we report on recent developments concerning PLGA nanoparticles prepared for cancer treatment. We review the methods used for the preparation and characterization of PLGA nanoparticles and their applications in the delivery of a number of active agents. Increasing experience in the field of preparation, characterization, and in vivo application of PLGA nanoparticles has provided the necessary momentum for promising future use of these agents in cancer treatment, with higher efficacy and fewer side effects.Keywords: nanotechnology, polymeric nanocarriers, targeting, anticancer agents, surface modification

  16. Design and synthesis of novel 4'-demethyl-4-deoxypodophyllotoxin derivatives as potential anticancer agents.

    Science.gov (United States)

    Zhu, Xiong; Fu, Junjie; Tang, Yan; Gao, Yuan; Zhang, Shijin; Guo, Qinglong

    2016-02-15

    A group of podophyllotoxin (PPT) derivatives (7a-j) were synthesized by conjugating aryloxyacetanilide moieties to the 4'-hydroxyl of 4'-demethyl-4-deoxypodophyllotoxin (DDPT), and their anticancer activity was evaluated. It was found that the most potent compound 7d inhibited the proliferation of three cancer cell lines with sub to low micromolar IC50 values. Furthermore, it was demonstrated that 7d induced cell cycle arrest in G2/M phase in MGC-803 cells, and regulated the expression of cell cycle check point proteins, such as cyclin A, cyclin B, CDK1, cdc25c, and p21. Finally, 4 mg/kg of 7d reduced the weights and volumes of HepG2 xenografts in mice. Our findings suggest that 7d might be a potential anticancer agent. PMID:26804229

  17. Explanation of the mechanism of carcinogenesis and syntheses of anticancer agents with high selectivity

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In 1979, the mechanism of chemical carcinogenesis, a challenging and difficult scientific problem pending for a number of years, was explained by Dai Qianhuan. The mechanism named di-region theory predicted that a carcinogen always metabolizes to form a special bi-functional alkylating agent. This agent induces cross-linkages between the complementary base pairs in DNA and switches on initial mutageneses in genomes including point and frameshift mutations. This, in turn, induces further deep mutageneses including the production of various chimeric chromosomes, deletions and other aberrations found in genomes. In the end this initiates carcinogenesis of the whole cell through the reverse transcription mechanism after a lengthy incubation period. Recently, this laboratory has verified that physical carcinogenesis, including the oncogenesis induced by radiation and asbestos as well as the carcinogenesis induced by endogenous factors such as estrogen or diethylstilbestrol switch on carcinogenesis by inducing the formation of cross-linkages between the complementary base pairs in DNA. Di-region theory has now been supported by many experimental observations such as mutational spectra of various carcinogens. The potential for carcinogenesis, teratogenesis, sterility and mutagenesis lumped together as genetic toxicity appears to originate almost uniformly from the cross-linking between complementary bases, i.e. malignant cross-linking, which is in accordance with di-region theory. Other forms of cross-linking between non-complementary bases, benign cross-linkings, show bi-functional alkylation anticancer activity but lack genetic toxicity. The predictable design and synthesis of a high selectivity anticancer agent with high efficacy and low genetic toxicity, a goal long pursued in cancer chemotherapy, have been realized for the first time in this laboratory by inhibiting malignant and heightening benign cross-linking using the principles of di-region theory. A series of

  18. Investigation of antioxidative and anticancer potentials of Streptomyces sp. MUM256 isolated from Malaysia mangrove soil

    Directory of Open Access Journals (Sweden)

    Tan Loh eTeng Hern

    2015-11-01

    Full Text Available A Streptomyces strain, MUM256 was isolated from Tanjung Lumpur mangrove soil in Malaysia. Characterization of the strain showed that it has properties consistent with those of the members of the genus Streptomyces. In order to explore the potential bioactivities, extract of the fermented broth culture of MUM256 was prepared with organic solvent extraction method. DPPH and SOD activity were utilized to examine the antioxidant capacity and the results have revealed the potency of MUM256 in superoxide anion scavenging activity in dose-dependent manner. The cytotoxicity of MUM256 extract was determined using cell viability assay against 8 different panels of human cancer cell lines. Among all the tested cancer cells, HCT116 was the most sensitive toward the extract treatment. At the highest concentration of tested extract, the result showed 2.3, 2.0 and 1.8 folds higher inhibitory effect against HCT116, HT29 and Caco-2 respectively when compared to normal cell line. This result has demonstrated that MUM256 extract was selectively cytotoxic towards colon cancer cell lines. In order to determine the constituents responsible for its bioactivities, the extract was then subjected to chemical analysis using GC-MS. The analysis resulted in the identification of chemical constituents including phenolic and pyrrolopyrazine compounds which may responsible for antioxidant and anticancer activities observed. Based on the findings of this study, the presence of bioactive constituents in MUM256 extract could be a potential source for the development of antioxidative and chemopreventive agents.

  19. Synthesis and Characterization of Celecoxib Derivatives as Possible Anti-Inflammatory, Analgesic, Antioxidant, Anticancer and Anti-HCV Agents

    Directory of Open Access Journals (Sweden)

    Amartya Basu

    2013-03-01

    Full Text Available A series of novel N-(3-substituted aryl/alkyl-4-oxo-1,3-thiazolidin-2-ylidene-4-[5-(4-methylphenyl-3-(trifluoromethyl-1H-pyrazol-1-yl]benzenesulfonamides 2a–e were synthesized by the addition of ethyl a-bromoacetate and anhydrous sodium acetate in dry ethanol to N-(substituted aryl/alkylcarbamothioyl-4-[5-(4-methylphenyl-3-(trifluoro-methyl-1H-pyrazol-1-yl]benzene sulfonamides 1a–e, which were synthesized by the reaction of alkyl/aryl isothiocyanates with celecoxib. The structures of the isolated products were determined by spectral methods and their anti-inflammatory, analgesic, antioxidant, anticancer and anti-HCV NS5B RNA-dependent RNA polymerase (RdRp activities evaluated. The compounds were also tested for gastric toxicity and selected compound 1a was screened for its anticancer activity against 60 human tumor cell lines. These investigations revealed that compound 1a exhibited anti-inflammatory and analgesic activities and further did not cause tissue damage in liver, kidney, colon and brain compared to untreated controls or celecoxib. Compounds 1c and 1d displayed modest inhibition of HCV NS5B RdRp activity. In conclusion, N-(ethylcarbamothioyl-4-[5-(4-methylphenyl-3-(trifluoromethyl-1H-pyrazol-1-yl]benzenesulfonamide (1a may have the potential to be developed into a therapeutic agent.

  20. Association Between hTERT rs2736100 Polymorphism and Sensitivity to Anti-cancer Agents

    Directory of Open Access Journals (Sweden)

    Julie eKim

    2013-08-01

    Full Text Available Background: The rs2736100 single nucleotide polymorphism (SNP is located in the intron 2 of human telomerase reverse transcriptase (hTERT gene. Recent genome-wide association studies (GWAS have consistently supported the strong association between this SNP and risk for multiple cancers. Given the important role of the hTERT gene and this SNP in cancer biology, we hypothesize that rs2736100 may also confer susceptibility to anti-cancer drug sensitivity. In this study we aim to investigate the correlation between the rs2736100 genotype and the responsiveness to anti-cancer agents in the NCI-60 cancer cell panel. Methods and Materials: The hTERT rs2736100 was genotyped in the NCI-60 cancer cell lines. The relative telomere length of each cell line was quantified using real-time PCR. The genotype was then correlated with publically available drug sensitivity data of two agents with telomerase-inhibition activity: Geldanamycin (HSP90 inhibitor and RHPS4/BRACO19 (G-quadruplex stabilizer as well as additional 110 commonly used agents with established mechanism of action. The association between rs2736100 and mutation status of TP53 gene was also tested.Results: The C allele of the SNP was significantly correlated with increased sensitivity to RHPS4/BRACO19 with an additive effect (r=-0.35, p=0.009 but not with Geldanamycin. The same allele was also significantly associated with sensitivity to antimitotic agents compared to other agents (p=0.003. The highest correlation was observed between the SNP and paclitaxel (r=-0.36, p=0.005. The telomere length was neither associated with rs2736100 nor with sensitivity to anti-cancer agents. The C allele of rs2736100 was significantly associated with increased mutation rate in TP53 gene (p=0.004.Conclusion: Our data suggested that the cancer risk allele of hTERT rs2736100 polymorphism may also affect the cancer cell response to both TERT inhibitor and anti-mitotic agents, which might be attributed to the elevated

  1. The application of click chemistry in the synthesis of agents with anticancer activity

    Directory of Open Access Journals (Sweden)

    Ma N

    2015-03-01

    Full Text Available Nan Ma,1–3 Ying Wang,3 Bing-Xin Zhao,3 Wen-Cai Ye,1,3 Sheng Jiang2 1Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 2Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, 3Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, People’s Republic of China Abstract: The copper(I-catalyzed 1,3-dipolar cycloaddition between alkynes and azides (click chemistry to form 1,2,3-triazoles is the most popular reaction due to its reliability, specificity, and biocompatibility. This reaction has the potential to shorten procedures, and render more efficient lead identification and optimization procedures in medicinal chemistry, which is a powerful modular synthetic approach toward the assembly of new molecular entities and has been applied in anticancer drugs discovery increasingly. The present review focuses mainly on the applications of this reaction in the field of synthesis of agents with anticancer activity, which are divided into four groups: topoisomerase II inhibitors, histone deacetylase inhibitors, protein tyrosine kinase inhibitors, and antimicrotubule agents. Keywords: topoisomerase II inhibitors, histone deacetylase inhibitors, protein tyrosine kinase inhibitors, antimicrotubule agents

  2. Designing piperlongumine-directed anticancer agents by an electrophilicity-based prooxidant strategy: A mechanistic investigation.

    Science.gov (United States)

    Yan, Wen-Jing; Wang, Qi; Yuan, Cui-Hong; Wang, Fu; Ji, Yuan; Dai, Fang; Jin, Xiao-Ling; Zhou, Bo

    2016-08-01

    Piperlongumine (PL), a natural electrophilic alkaloid bearing two α, β-unsaturated imides, is a promising anticancer molecule by targeting the stress response to reactive oxygen species (ROS). Considering that ROS generation depends on electrophilicity of PL, PL-CL was designed as its analog by introducing the α-substituent chlorine on the lactam ring to increase moderately its electrophilicity. In comparison with the parent molecule, this molecule was identified as a stronger ROS (O2(∙-) and H2O2) inducer and cytotoxic agent, and manifested more than 15-fold selectivity toward A549 cells over normal WI-38 cells. Mechanistic study uncovers for the first time that the selenoprotein thioredoxin reductase (TrxR) is one of the targets by which PL-CL promotes the ROS generation. Stronger intracellular TrxR inhibition and higher accumulation of ROS (O2(∙-) and H2O2) are responsible for more effective S-phase arrest and mitochondria-mediated apoptotic induction of A549 cells by PL-CL than PLvia p53-p21-cyclinA/CDK2 and ASK1-JNK/p38 signaling cascade pathways, respectively. This work provides an example of successfully designing PL-directed anticancer agent by an electrophilicity-based prooxidant (ROS-generating agent) strategy and gives added confidence for extending this strategy to other natural products. PMID:27233942

  3. Current development of the second generation of mTOR inhibitors as anticancer agents

    Institute of Scientific and Technical Information of China (English)

    Hong-Yu Zhou; Shi-Le Huang

    2012-01-01

    The mammalian target of rapamycin (mTOR),a serine/threonine protein kinase,acts as a “master switch” for cellular anabolic and catabolic processes,regulating the rate of cell growth and proliferation.Dysregulation of the mTOR signaling pathway occurs frequently in a variety of human tumors,and thus,mTOR has emerged as an important target for the design of anticancer agents.mTOR is found in two distinct multiprotein complexes within cells,mTORC1 and mTORC2.These two complexes consist of unique mTOR-interacting proteins and are regulated by different mechanisms.Enormous advances have been made in the development of drugs known as mTOR inhibitors.Rapamycin,the first defined inhibitor of mTOR,showed effectiveness as an anticancer agent in various preclinical models.Rapamycin analogues (rapalogs) with better pharmacologic properties have been developed.However,the clinical success of rapalogs has been limited to a few types of cancer.The discovery that mTORC2 directly phosphorylates Akt,an important survival kinase,adds new insight into the role of mTORC2 in cancer.This novel finding prompted efforts to develop the second generation of mTOR inhibitors that are able to target both mTORC1 and mTORC2.Here,we review the recent advances in the mTOR field and focus specifically on the current development of the second generation of mTOR inhibitors as anticancer agents.

  4. The in vitro metabolism of phospho-sulindac amide, a novel potential anticancer agent

    OpenAIRE

    Xie, Gang; Cheng, Ka-Wing; Huang, Liqun; Rigas, Basil

    2014-01-01

    Phospho-sulindac amide (PSA) is a novel potential anti-cancer and anti-inflammatory agent. Here we report the metabolism of PSA in vitro. PSA was rapidly hydroxylated at its butane-phosphate moiety to form two di-hydroxyl-PSA and four mono-hydroxyl-PSA metabolites in mouse and human liver microsomes. PSA also can be oxidized or reduced at its sulindac moiety to form PSA sulfone and PSA sulfide, respectively. PSA was mono-hydroxylated and cleared more rapidly in mouse liver microsomes than in ...

  5. Investigation of Degradation Properties of Poly(lactide-co-glycolide) Matrix for Anticancer Agent Delivery

    International Nuclear Information System (INIS)

    Poly(lactide-co-glycolide)(PLA50GA50) is a biodegradable and biocompatible polymer. It offers tremendous potential as a basis for drug delivery, either as drug delivery system alone or in conjugate with a medical device. The PLA50GA50 is the material of choice for relatively shorter-duration applications, while the homopolymer PLA (poly-L-lactide) and PGA (polyglycolide) are preferred for longer term delivery of drugs. This paper discusses the degradation properties of poly(lactide-co-glycolide)(PLA50GA50) at inherent viscosity of 0.89 dL/g as preliminary studies for anticancer agent delivery.

  6. Moringa oleifera as an Anti-Cancer Agent against Breast and Colorectal Cancer Cell Lines

    Science.gov (United States)

    Al-Asmari, Abdulrahman Khazim; Albalawi, Sulaiman Mansour; Athar, Md Tanwir; Khan, Abdul Quaiyoom; Al-Shahrani, Hamoud; Islam, Mozaffarul

    2015-01-01

    In this study we investigated the anti-cancer effect of Moringa oleifera leaves, bark and seed extracts. When tested against MDA-MB-231 and HCT-8 cancer cell lines, the extracts of leaves and bark showed remarkable anti-cancer properties while surprisingly, seed extracts exhibited hardly any such properties. Cell survival was significantly low in both cells lines when treated with leaves and bark extracts. Furthermore, a striking reduction (about 70–90%) in colony formation as well as cell motility was observed upon treatment with leaves and bark. Additionally, apoptosis assay performed on these treated breast and colorectal cancer lines showed a remarkable increase in the number of apoptotic cells; with a 7 fold increase in MD-MB-231 to an increase of several fold in colorectal cancer cell lines. However, no significant apoptotic cells were detected upon seeds extract treatment. Moreover, the cell cycle distribution showed a G2/M enrichment (about 2–3 fold) indicating that these extracts effectively arrest the cell progression at the G2/M phase. The GC-MS analyses of these extracts revealed numerous known anti-cancer compounds, namely eugenol, isopropyl isothiocynate, D-allose, and hexadeconoic acid ethyl ester, all of which possess long chain hydrocarbons, sugar moiety and an aromatic ring. This suggests that the anti-cancer properties of Moringa oleifera could be attributed to the bioactive compounds present in the extracts from this plant. This is a novel study because no report has yet been cited on the effectiveness of Moringa extracts obtained in the locally grown environment as an anti-cancer agent against breast and colorectal cancers. Our study is the first of its kind to evaluate the anti-malignant properties of Moringa not only in leaves but also in bark. These findings suggest that both the leaf and bark extracts of Moringa collected from the Saudi Arabian region possess anti-cancer activity that can be used to develop new drugs for treatment of

  7. Pharmacophore modeling and in silico toxicity assessment of potential anticancer agents from African medicinal plants

    Directory of Open Access Journals (Sweden)

    Ntie-Kang F

    2016-07-01

    Full Text Available Fidele Ntie-Kang,1,2,* Conrad Veranso Simoben,1,2,* Berin Karaman,1 Valery Fuh Ngwa,3 Philip Neville Judson,4 Wolfgang Sippl,1 Luc Meva’a Mbaze5 1Department of Pharmaceutical Chemistry, Martin-Luther University of Halle-Wittenberg, Halle (Saale, Germany; 2Department of Chemistry, University of Buea, Buea, Cameroon; 3Interuniversity Institute For Biostatistics and Statistical Bioinformatics (I-BioStat, University of Hasselt, Hasselt, Belgium; 4Chemical Bioactivity Information Centre, Harrogate, UK; 5Department of Chemistry, Faculty of Science, University of Douala, Douala, Cameroon *These authors contributed equally to this work Abstract: Molecular modeling has been employed in the search for lead compounds of chemotherapy to fight cancer. In this study, pharmacophore models have been generated and validated for use in virtual screening protocols for eight known anticancer drug targets, including tyrosine kinase, protein kinase B β, cyclin-dependent kinase, protein farnesyltransferase, human protein kinase, glycogen synthase kinase, and indoleamine 2,3-dioxygenase 1. Pharmacophore models were validated through receiver operating characteristic and Güner–Henry scoring methods, indicating that several of the models generated could be useful for the identification of potential anticancer agents from natural product databases. The validated pharmacophore models were used as three-dimensional search queries for virtual screening of the newly developed AfroCancer database (~400 compounds from African medicinal plants, along with the Naturally Occurring Plant-based Anticancer Compound-Activity-Target dataset (comprising ~1,500 published naturally occurring plant-based compounds from around the world. Additionally, an in silico assessment of toxicity of the two datasets was carried out by the use of 88 toxicity end points predicted by the Lhasa’s expert knowledge-based system (Derek, showing that only an insignificant proportion of the promising

  8. The Comparison of MTT and CVS Assays for the Assessment of Anticancer Agent Interactions.

    Directory of Open Access Journals (Sweden)

    Lidia Śliwka

    Full Text Available Multiple in vitro tests are widely applied to assess the anticancer activity of new compounds, including their combinations and interactions with other drugs. The MTT (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide assay is one of the most commonly used assays to assess the efficacy and interactions of anticancer agents. However, it can be significantly influenced by compounds that modify cell metabolism and reaction conditions. Therefore, several assays are sometimes used to screen for potential anticancer drugs. However, the majority of drug interactions are evaluated only with this single method. The aim of our studies was to verify whether the choice of an assay has an impact on determining the type of interaction and to identify the source of discrepancies. We compared the accuracy of MTT and CVS (crystal violet staining assays in the interaction of two compounds characterized by similar anticancer activity: isothiocyanates (ITCs and Selol. Confocal microscopy studies were carried out to assess the influence of these compounds on the reactive oxygen species (ROS level, mitochondrial membrane potential, dead-to-live cell ratio and MTT-tetrazolium salt reduction rate. The MTT assay was less reliable than CVS. The MTT test of Selol and 2-oxoheptyl ITC, which affected the ROS level and MTT reduction rate, gave false negative (2-oxoheptyl ITC or false positive (Selol results. As a consequence, the MTT assay identified an antagonistic interaction between Selol and ITC, while the metabolism-independent CVS test identified an additive or synergistic interaction. In this paper, we show for the first time that the test assay may change the interpretation of the compound interaction. Therefore, the test method should be chosen with caution, considering the mechanism of action of the compound.

  9. The Comparison of MTT and CVS Assays for the Assessment of Anticancer Agent Interactions.

    Science.gov (United States)

    Śliwka, Lidia; Wiktorska, Katarzyna; Suchocki, Piotr; Milczarek, Małgorzata; Mielczarek, Szymon; Lubelska, Katarzyna; Cierpiał, Tomasz; Łyżwa, Piotr; Kiełbasiński, Piotr; Jaromin, Anna; Flis, Anna; Chilmonczyk, Zdzisław

    2016-01-01

    Multiple in vitro tests are widely applied to assess the anticancer activity of new compounds, including their combinations and interactions with other drugs. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay is one of the most commonly used assays to assess the efficacy and interactions of anticancer agents. However, it can be significantly influenced by compounds that modify cell metabolism and reaction conditions. Therefore, several assays are sometimes used to screen for potential anticancer drugs. However, the majority of drug interactions are evaluated only with this single method. The aim of our studies was to verify whether the choice of an assay has an impact on determining the type of interaction and to identify the source of discrepancies. We compared the accuracy of MTT and CVS (crystal violet staining) assays in the interaction of two compounds characterized by similar anticancer activity: isothiocyanates (ITCs) and Selol. Confocal microscopy studies were carried out to assess the influence of these compounds on the reactive oxygen species (ROS) level, mitochondrial membrane potential, dead-to-live cell ratio and MTT-tetrazolium salt reduction rate. The MTT assay was less reliable than CVS. The MTT test of Selol and 2-oxoheptyl ITC, which affected the ROS level and MTT reduction rate, gave false negative (2-oxoheptyl ITC) or false positive (Selol) results. As a consequence, the MTT assay identified an antagonistic interaction between Selol and ITC, while the metabolism-independent CVS test identified an additive or synergistic interaction. In this paper, we show for the first time that the test assay may change the interpretation of the compound interaction. Therefore, the test method should be chosen with caution, considering the mechanism of action of the compound. PMID:27196402

  10. Amino acid esters substituted phosphorylated emtricitabine and didanosine derivatives as antiviral and anticancer agents.

    Science.gov (United States)

    Sekhar, Kuruva Chandra; Janardhan, Avilala; Kumar, Yellapu Nanda; Narasimha, Golla; Raju, Chamarthi Naga; Ghosh, S K

    2014-07-01

    Owing to the promising antiviral activity of amino acid ester-substituted phosphorylated nucleosides in the present study, a series of phosphorylated derivatives of emtricitabine and didanosine substituted with bioactive amino acid esters at P-atom were synthesized. Initially, molecular docking studies were screened to predict their molecular interactions with hemagglutinin-neuraminidase protein of Newcastle disease virus and E2 protein of human papillomavirus. The title compounds were screened for their antiviral ability against Newcastle disease virus (NDV) by their in ovo study in embryonated chicken eggs. Compounds 5g and 9c exposed well mode of interactions with HN protein and also exhibited potential growth of NDV inhibition. The remaining compounds exhibited better growth of NDV inhibition than their parent molecules, i.e., emtricitabine (FTC) and didanosine (ddI). In addition, the in vitro anticancer activity of all the title compounds were screenedagainst HeLa cell lines at 10 and 100 μg/mL concentrations. The compounds 5g and 9c showed an effective anticancer activity than that of the remaining title compounds with IC50 values of 40 and 60 μg/mL, respectively. The present in silico and in ovo antiviral and in vitro anticancer results of the title compounds are suggesting that the amino acid ester-substituted phosphorylated FTC and ddI derivatives, especially 5g and 9c, can be used as NDV inhibitors and anticancer agents for the control and management of viral diseases with cancerous condition. PMID:24789416

  11. Ferns and lycopods--a potential treasury of anticancer agents but also a carcinogenic hazard.

    Science.gov (United States)

    Tomšík, Pavel

    2014-06-01

    Many species of seedless vascular plants-ferns and lycopods-have been used as food and folk medicine since ancient times. Some of them have become the focus of intensive research concerning their anticancer properties. Studies on the anticancer effect of crude extracts are being increasingly replaced by bioactivity-guided fractionation, as well as detailed assessment of the mechanism of action. Numerous compounds-especially flavonoids such as amentoflavone and protoapigenone, and also simpler phenolic compounds, steroids, alkaloids and terpenoids-were isolated and found to be cytotoxic, particularly pro-apoptotic, or to induce cell cycle arrest in cancer cell lines in vitro. In in vivo experiments, some fern-derived compounds inhibited tumour growth with little toxicity. On the other hand, many ferns-not only the well-known Bracken (Pteridium)-may pose a significant hazard to human health due to the fact that they contain carcinogenic sesquiterpenoids and their analogues. The objective of this review is to summarise the recent state of research on the anticancer properties of ferns and lycopods, with a focus on their characteristic bioactive constituents. The carcinogenic hazard posed by ferns is also mentioned. PMID:24123573

  12. Design, synthesis, and mechanistic studies of Sansalvamide A derivatives as anti-cancer agents

    OpenAIRE

    Alexander, Leslie Diane

    2012-01-01

    Sansalvamide A (SanA) is a cyclic depsipeptide that was isolated from a marine fungus and demonstrates mid- micromolar anti-cancer activity in the NCI 60-cell line panel. Our laboratory has synthesized over 100 peptide derivatives of this molecule, 5 of which were contributed by the author of this dissertation. The design and solution-phase synthesis of these derivatives is described in Chapter 2. The author was also responsible for attaching PEG-biotin and fluorescein tags to lead SanA deriv...

  13. ER maleate is a novel anticancer agent in oral cancer: implications for cancer therapy

    Science.gov (United States)

    Fu, Guodong; Somasundaram, Raj Thani; Jessa, Fatima; Srivastava, Gunjan; MacMillan, Christina; Witterick, Ian; Walfish, Paul G.; Ralhan, Ranju

    2016-01-01

    ER maleate [10-(3-Aminopropyl)-3, 4-dimethyl-9(10H)-acridinone maleate] identified in a kinome screen was investigated as a novel anticancer agent for oral squamous cell carcinoma (OSCC). Our aim was to demonstrate its anticancer effects, identify putative molecular targets and determine their clinical relevance and investigate its chemosensitization potential for platinum drugs to aid in OSCC management. Biologic effects of ER maleate were determined using oral cancer cell lines in vitro and oral tumor xenografts in vivo. mRNA profiling, real time PCR and western blot revealed ER maleate modulated the expression of polo-like kinase 1 (PLK1) and spleen tyrosine kinase (Syk). Their clinical significance was determined in oral SCC patients by immunohistochemistry and correlated with prognosis by Kaplan-Meier survival and multivariate Cox regression analyses. ER maleate induced cell apoptosis, inhibited proliferation, colony formation, migration and invasion in oral cancer cells. Imagestream analysis revealed cell cycle arrest in G2/M phase and increased polyploidy, unravelling deregulation of cell division and cell death. Mechanistically, ER maleate decreased expression of PLK1 and Syk, induced cleavage of PARP, caspase9 and caspase3, and increased chemosensitivity to carboplatin; significantly suppressed tumor growth and increased antitumor activity of carboplatin in tumor xenografts. ER maleate treated tumor xenografts showed reduced PLK1 and Syk expression. Clinical investigations revealed overexpression of PLK1 and Syk in oral SCC patients that correlated with disease prognosis. Our in vitro and in vivo findings provide a strong rationale for pre-clinical efficacy of ER maleate as a novel anticancer agent and chemosensitizer of platinum drugs for OSCC. PMID:26934445

  14. Nature promises new anticancer agents: Interplay with the apoptosis-related BCL2 gene family.

    Science.gov (United States)

    Christodoulou, Maria-Ioanna; Kontos, Christos K; Halabalaki, Maria; Skaltsounis, Alexios-Leandros; Scorilas, Andreas

    2014-03-01

    Natural products display special attributes in the treatment and prevention of a variety of human disorders including cancer. Their therapeutic capacities along with the fact that nature comprises a priceless pool of new compounds have attracted the interest of researchers worldwide. A significant number of organic compounds from terrestrial and marine organisms exhibit anticancer properties as attested by both in vitro and in vivo studies. Emerging evidence supporting the antineoplastic activity of natural compounds has rendered them promising agents in the fight against cancer. As a result, numerous natural compounds or their derivatives have entered clinical practice and are currently in the forefront of chemotherapeutics, showing beneficial effects for cancer patients. Induction of apoptosis seems to be the major mechanism of action induced by these natural agents in the race against cancer. This is mainly achieved through modulations of the expression of B-cell CLL/lymphoma 2 (BCL2) family members. These molecules appear to be the pivotal players determining cellular fate. In the current review, we provide a comprehensive overview of the major alterations in the gene and/or protein levels of BCL2-family members evoked in cancer cells after treatment with a gamut of natural compounds. The data cited suggest the need for exploitation of newly discovered natural products that, along with the improvement of currently employed chemotherapeutics, will significantly enrich the anticancer armamentarium. PMID:23848203

  15. Antitumor efficacy of conventional anticancer drugs is enhanced by the vascular targeting agent ZD6126

    International Nuclear Information System (INIS)

    Purpose: The present report reviews the preclinical data on combined chemotherapy/vascular targeting agent treatments. Basic principles are illustrated in studies evaluating the antitumor efficacy of the vascular targeting agent ZD6126 (N-acetylcochinol-O-phosphate) when combined with the anticancer drug cisplatin in experimental rodent (KHT sarcoma) and human renal (Caki-1) tumor models. Methods and Materials: C3H/HeJ and NCR/nu-nu mice bearing i.m. tumors were injected i.p. with ZD6126 (0-150 mg/kg) or cisplatin (0-20 mg/kg) either alone or in combination. Tumor response to treatment was assessed by clonogenic cell survival. Results: Treatment with ZD6126 was found to damage existing neovasculature, leading to a rapid vascular shutdown. Histologic evaluation showed dose-dependent morphologic damage of tumor cells within a few hours after drug exposure, followed by extensive central tumor necrosis and neoplastic cell death as a result of prolonged ischemia. ZD6126 doses that led to pathophysiologic effects also enhanced the tumor cell killing of cisplatin when administered either 24 h before or 1-24 h after chemotherapy. In both tumor models, the administration of a 150 mg/kg dose of ZD6126 1 h after a range of doses of cisplatin resulted in an increase in tumor cell kill 10-500-fold greater than that seen with chemotherapy alone. In contrast, the inclusion of the antivascular agent did not increase bone marrow stem cell toxicity associated with this anticancer drug. Conclusion: The results obtained in the KHT and Caki-1 tumor models indicate that ZD6126 effectively enhanced the antitumor effects of cisplatin therapy. These findings are representative of the marked enhancements generally observed when vascular targeting agents are combined with chemotherapy in solid tumor therapy

  16. Theobroma cacao: Review of the Extraction, Isolation, and Bioassay of Its Potential Anti-cancer Compounds

    OpenAIRE

    Baharum, Zainal; Akim, Abdah Md; Hin, Taufiq Yap Yun; Hamid, Roslida Abdul; Kasran, Rosmin

    2016-01-01

    Plants have been a good source of therapeutic agents for thousands of years; an impressive number of modern drugs used for treating human diseases are derived from natural sources. The Theobroma cacao tree, or cocoa, has recently garnered increasing attention and become the subject of research due to its antioxidant properties, which are related to potential anti-cancer effects. In the past few years, identifying and developing active compounds or extracts from the cocoa bean that might exert...

  17. THE ROLE OF RED PIGMENT PRODIGIOSIN FROM BACTERIA OF EARTHWORM GUT AS AN ANTICANCER AGENT

    Directory of Open Access Journals (Sweden)

    Sruthy P.B.

    2014-12-01

    Full Text Available Earthworms are the most ancient invertebrate animals on earth which can be used as a good source of pharmaceutical compounds. A study was carried out to find out the distribution of microorganisms in the gut of earthworm, Eudrilus eugeniae. Significant number of microbial populations in the gut of earthworm was observed and it was gradually increased from the initial day to final day of composting. Pigmented colonies of bacteria from earthworm gut were selectively isolated, the pigment was extracted from the culture broth and a presumptive test was carried out for the confirmation of prodigiosin. The pigment component was separated using thin layer chromatography and the structural elucidation of the compound was performed using U.V. spectroscopy. The inhibitory effect of prodigiosin on bacterial pathogens was studied and the results confirmed the antibacterial activity against gram positive bacteria. The anticancer activity of the prodigiosin pigment was evaluated under in vitro conditions against the breast cancer cell lines and it was observed that prodigiosin induced the apoptosis in MCF-7 cell lines in a dose dependent manner. Then the potential isolate was subjected to morphological and biochemical analysis and it was confirmed that the colonies were of Serratia marcescens. The results obtained from the present study indicated that earthworm gut is promising and could be a vital source of habitat possessing antimicrobial and anticancer activity.

  18. Isolation of Cells Specialized in Anticancer Alkaloid Metabolism by Fluorescence-Activated Cell Sorting.

    Science.gov (United States)

    Carqueijeiro, Inês; Guimarães, Ana Luísa; Bettencourt, Sara; Martínez-Cortés, Teresa; Guedes, Joana G; Gardner, Rui; Lopes, Telma; Andrade, Cláudia; Bispo, Cláudia; Martins, Nuno Pimpão; Andrade, Paula; Valentão, Patrícia; Valente, Inês M; Rodrigues, José A; Duarte, Patrícia; Sottomayor, Mariana

    2016-08-01

    Plant specialized metabolism often presents a complex cell-specific compartmentation essential to accomplish the biosynthesis of valuable plant natural products. Hence, the disclosure and potential manipulation of such pathways may depend on the capacity to isolate and characterize specific cell types. Catharanthus roseus is the source of several medicinal terpenoid indole alkaloids, including the low-level anticancer vinblastine and vincristine, for which the late biosynthetic steps occur in specialized mesophyll cells called idioblasts. Here, the optical, fluorescence, and alkaloid-accumulating properties of C. roseus leaf idioblasts are characterized, and a methodology for the isolation of idioblast protoplasts by fluorescence-activated cell sorting is established, taking advantage of the distinctive autofluorescence of these cells. This achievement represents a crucial step for the development of differential omic strategies leading to the identification of candidate genes putatively involved in the biosynthesis, pathway regulation, and transmembrane transport leading to the anticancer alkaloids from C. roseus. PMID:27356972

  19. Isatin Derived Spirocyclic Analogues with α-Methylene-γ-butyrolactone as Anticancer Agents: A Structure-Activity Relationship Study.

    Science.gov (United States)

    Rana, Sandeep; Blowers, Elizabeth C; Tebbe, Calvin; Contreras, Jacob I; Radhakrishnan, Prakash; Kizhake, Smitha; Zhou, Tian; Rajule, Rajkumar N; Arnst, Jamie L; Munkarah, Adnan R; Rattan, Ramandeep; Natarajan, Amarnath

    2016-05-26

    Design, synthesis, and evaluation of α-methylene-γ-butyrolactone analogues and their evaluation as anticancer agents is described. SAR identified a spirocyclic analogue 19 that inhibited TNFα-induced NF-κB activity, cancer cell growth and tumor growth in an ovarian cancer model. A second iteration of synthesis and screening identified 29 which inhibited cancer cell growth with low-μM potency. Our data suggest that an isatin-derived spirocyclic α-methylene-γ-butyrolactone is a suitable core for optimization to identify novel anticancer agents. PMID:27077228

  20. 2-Hydroxypropyl-β-Cyclodextrin Acts as a Novel Anticancer Agent.

    Directory of Open Access Journals (Sweden)

    Masako Yokoo

    Full Text Available 2-Hydroxypropyl-β-cyclodextrin (HP-β-CyD is a cyclic oligosaccharide that is widely used as an enabling excipient in pharmaceutical formulations, but also as a cholesterol modifier. HP-β-CyD has recently been approved for the treatment of Niemann-Pick Type C disease, a lysosomal lipid storage disorder, and is used in clinical practice. Since cholesterol accumulation and/or dysregulated cholesterol metabolism has been described in various malignancies, including leukemia, we hypothesized that HP-β-CyD itself might have anticancer effects. This study provides evidence that HP-β-CyD inhibits leukemic cell proliferation at physiologically available doses. First, we identified the potency of HP-β-CyD in vitro against various leukemic cell lines derived from acute myeloid leukemia (AML, acute lymphoblastic leukemia and chronic myeloid leukemia (CML. HP-β-CyD treatment reduced intracellular cholesterol resulting in significant leukemic cell growth inhibition through G2/M cell-cycle arrest and apoptosis. Intraperitoneal injection of HP-β-CyD significantly improved survival in leukemia mouse models. Importantly, HP-β-CyD also showed anticancer effects against CML cells expressing a T315I BCR-ABL mutation (that confers resistance to most ABL tyrosine kinase inhibitors, and hypoxia-adapted CML cells that have characteristics of leukemic stem cells. In addition, colony forming ability of human primary AML and CML cells was inhibited by HP-β-CyD. Systemic administration of HP-β-CyD to mice had no significant adverse effects. These data suggest that HP-β-CyD is a promising anticancer agent regardless of disease or cellular characteristics.

  1. In vitro anticancer activity of microbial isolates from diverse habitats

    Directory of Open Access Journals (Sweden)

    Angel Treasa Thomas

    2011-06-01

    Full Text Available Extracts from natural products, especially microorganisms, have served as a valuable source of diverse molecules in many drug discovery efforts and led to the discovery of several important drugs. Identification of microbial strains having promising biological activities and purifying the bio-molecules responsible for the activities, have led to the discovery of many bioactive molecules. Extracellular, as well as intracellular, extracts of the metabolites of thirty-six bacterial and twenty-four fungal isolates, grown under unusual conditions such as high temperature, high salt and low sugar concentrations, were in vitro tested for their cytotoxic potential on various cancer cell lines. The extracts were screened on HeLa and MCF-7 cell lines to study the cytotoxic potential. Nuclear staining and flow cytometric studies were carried out to assess the potential of the extracts in arresting the cell cycle. The crude ethylacetate extract of isolate F-21 showed promising results by MTT assay with IC50 as low as 20.37±0.36 µg/mL on HeLa, and 44.75±0.81 µg/mL on MCF-7 cells, comparable with Cisplatin. The isolate F-21 was identified as Aspergillus sp. Promising results were also obtained with B-2C and B-4E strains. Morphological studies, biochemical tests and preliminary chemical investigation of the extracts were also carried out.Extratos de produtos naturais, especialmente de microrganismos, constituíram-se em fonte valiosa de diversas moléculas em muitas descobertas de fármacos e levaram à descoberta de fármacos importantes. A identificação de espécies microbianas que apresentam atividade biológica e a purificação de biomoléculas responsáveis pelas atividades levou à descoberta de muitas moléculas bioativas. Extratos extracelulares tanto quanto intracelulares de metabólitos de 36 isolados de bactérias e 24 isolados de fungos, que cresceram sob condições não usuais, como alta temperatura, alta concentração de sal e baixa

  2. Honey as a Potential Natural Anticancer Agent: A Review of Its Mechanisms

    Directory of Open Access Journals (Sweden)

    Sarfraz Ahmed

    2013-01-01

    Full Text Available The main treatment for cancer is by using chemotherapy and radiotherapy which themselves are toxic to other viable cells of the body. Recently, there are many studies focusing on the use of natural products for cancer prevention and treatment. Of these natural products, honey has been extensively researched. The mechanism of the anti-cancer activity of honey as chemopreventive and therapeutic agent has not been completely understood. The possible mechanisms are due to its apoptotic, antiproliferative, antitumor necrosis factor (anti-TNF, antioxidant, anti-inflammatory, estrogenic and immunomodulatory activities. We collate the findings of several studies published in the literature in order to understand the mechanism of its action.

  3. A Possible Anticancer Agent, Type III Interferon, Activates Cell Death Pathways and Produces Antitumor Effects

    Directory of Open Access Journals (Sweden)

    Masatoshi Tagawa

    2011-01-01

    Full Text Available Recently identified interleukin-28 and -29 belong to a novel type III interferon (IFN family, which could have distinct biological properties from type I and II IFNs. Type I IFNs, IFN-α/β, have been clinically applied for treating a certain kind of malignancies for over 30 years, but a wide range of the adverse effects hampered the further clinical applications. Type III IFNs, IFN-λs, have similar signaling pathways as IFN-α/β and inhibits proliferation of tumor cells through cell cycle arrest or apoptosis. Restricted patterns of type III IFN receptor expression in contrast to ubiquitously expressed IFN-α/β receptors suggest that type III IFNs have limited cytotoxicity to normal cells and can be a possible anticancer agent. In this paper, we summarize the current knowledge on the IFN-λs-mediated tumor cell death and discuss the functional difference between type I and III IFNs.

  4. Lesson Learned from Nature for the Development of Novel Anti-Cancer Agents: Implication of Isoflavone, Curcumin, and their Synthetic Analogs

    OpenAIRE

    Sarkar, Fazlul H; Li, Yiwei; Wang, Zhiwei; Padhye, Subhash

    2010-01-01

    In recent years, naturally occurring dietary compounds have received greater attention in the field of cancer prevention and treatment research. Among them, isoflavone genistein and curcumin are very promising anti-cancer agents because of their non-toxic and potent anti-cancer properties. However, it is important to note that the low water solubility, poor in vivo bioavailability and unacceptable pharmacokinetic profile of these natural compounds limit their efficacy as anti-cancer agents fo...

  5. In vitro evaluation of anticancer potentials of lupeol isolated from Elephantopus scaber L. on MCF-7 cell line

    Directory of Open Access Journals (Sweden)

    Daisy Pitchai

    2014-01-01

    Full Text Available Lupeol is a triterpenoid, present in most of the medicinally effective plants and possess a wide range of biological activity against human diseases. The present study aims at evaluating the anticancer potentials of lupeol, isolated from the leaves of Elephantopus scaber L. and thereby explores its action on key cancer marker, Bcl-2. The effect of lupeol on the cell viability of MCF-7 was determined by MTT and lactate dehydrogenase assays at different concentrations. The efficacy of the compound to induce cell death was analyzed using AO/EtBr staining. Phase contrast microscopic analysis provided the changes in cell morphology of the compound treated normal breast cells (MCF-10A and MCF-7 cells. The expression of Bcl-2 and Bcl-xL proteins in the normal, cancer and lupeol treated cancer cell was analyzed by western blotting. Lupeol induced an effective change in the cell viability of MCF-7 cells with IC 50 concentration as 80 μM. Induction of cell death, change in cell morphology and population of the cancer cells was observed in the lupeol treated cells, but the normal cells were not affected. The compound effectively downregulated Bcl-2 and Bcl-xL protein expressions, which directly contribute for the induction of MCF-7 cell apoptosis. Conclusion: Thus, lupeol acts as an anticancer agent against MCF-7 cells and is a potent phytodrug to be explored further for its cytotoxic mechanism.

  6. Design, Synthesis, and Biological Evaluation of Novel Selenium (Se-NSAID) Molecules as Anticancer Agents.

    Science.gov (United States)

    Plano, Daniel; Karelia, Deepkamal N; Pandey, Manoj K; Spallholz, Julian E; Amin, Shantu; Sharma, Arun K

    2016-03-10

    The synthesis and anticancer evaluation of novel selenium-nonsteroidal anti-inflammatory drug (Se-NSAID) hybrid molecules are reported. The Se-aspirin analogue 8 was identified as the most effective agent in reducing the viability of different cancer cell lines, particularly colorectal cancer (CRC) cells, was more selective toward cancer cells than normal cells, and was >10 times more potent than 5-FU, the current therapy for CRC. Compound 8 inhibits CRC growth via the inhibition of the cell cycle in G1 and G2/M phases and reduces the cell cycle markers like cyclin E1 and B1 in a dose dependent manner; the inhibition of the cell cycle may be dependent on the ability of 8 to induce p21 expression. Furthermore, 8 induces apoptosis by activating caspase 3/7 and PARP cleavage, and its longer exposure causes increase in intracellular ROS levels in CRC cells. Taken together, 8 has the potential to be developed further as a chemotherapeutic agent for CRC. PMID:26750401

  7. Poor oral bioavailability of a promising anticancer agent andrographolide is due to extensive metabolism and efflux by P-glycoprotein.

    Science.gov (United States)

    Ye, Ling; Wang, Tao; Tang, Lan; Liu, Wei; Yang, Zhen; Zhou, Juan; Zheng, Zhijie; Cai, Zheng; Hu, Ming; Liu, Zhongqiu

    2011-11-01

    Andrographolide (AP), isolated from Andrographis paniculata (Burm. F.) Nees, is an anticancer agent with significant clinical potential. This study determined its oral bioavailability and how intestinal disposition affects its bioavailability. Pharmacokinetics was evaluated in rats. Intestinal disposition was determined using a single-pass rat intestinal perfusion model and the cultured Caco-2 cells and Madin-Darby canine kidney II cells over expressing human P-gp (MDR1-MDCKII). Absolute bioavailability of AP was 2.67%. In the duodenum and jejunum, AP was rapidly metabolized to a sulfonate, identified as 14-deoxy-12-sulfo- andrographolide. AP was also rapidly metabolized by liver S9 fraction and in blank perfusates collected from duodenum and jejunum. The apparent permeability (P(app) ) of AP from basolateral (B) to apical (A) (4.94 × 10 cm/s) in the Caco-2 model was four times higher than the P(app) from A to B (1.14 × 10(-5) cm/s). Moreover, AP was significantly more permeable in the B to A direction than the opposite direction in MDR1-MDCKII cells. In the perfusion model, the effective permeability (P*(eff) ) for AP was highest in the duodenum, followed by jejunum, and then ileum and colon. In the ileum and colon, the P*(eff) for AP was significantly increased by verapamil, a P-glycoprotein (P-gp) inhibitor. AP has poor oral bioavailability because of its rapid biotransformation and efflux by P-gp. PMID:21721007

  8. Hematotoxicity response in rats by the novel copper-based anticancer agent: casiopeina II

    International Nuclear Information System (INIS)

    The in vivo toxicity of the novel copper-based anticancer agent, casiopeina II (Cu(4,7-dimethyl-1,10-phenanthroline)(glycine)NO3) (CII), was investigated. Casiopeinas are a family of copper-coordinated complexes that have shown promising anticancer activity. The major toxic effect attributed to a single i.v. administration of CII (5 mg/kg dose) in the rat was an hemolytic anemia (reduced hemoglobin concentration (HB), red blood cell (RBC) count and packed cell volume (PCV) accompanied by a marked neutrophilic leukocytosis) 12 h and 5 days after administration, attributed to a direct erythrocyte damage. Increased reticulocyte levels and presence of normoblasts in peripheral blood 5 days post-administration indicated an effective erythropoietic response with recovery at 15 days. Increase in spleen weight and the morphological evidence of congestion of the red pulp (RP) with erythrocytes (E) resulting in a higher ratio of red to white pulp (WP) was consistent with increased uptake of damaged erythrocytes by the reticuloendothelial system observed by histopathology and electron microscopy. Extramedullary hemopoiesis was markedly increased at 5 days giving further evidence of a regenerative erythropoietic response that had an effective recovery by 15 days. Morphological changes in spleen cellularity were consistent with hematotoxicity, mainly a reduction of the red pulp/white pulp ratio, increase in erythrocyte content at 12 h, and an infiltration of nucleated cells in the red pulp at 5 days, with a tendency towards recovery 15 days after administration. The erythrocyte damage is attributed to generation of free radicals and oxidative damage on the membrane and within cells resulting from the reduction of Cu(II) and the probable dissociation of the CII complex

  9. Recent Development of Copolymeric Delivery System for Anticancer Agents Based on Cyclodextrin Derivatives.

    Science.gov (United States)

    Feng, Runliang; Deng, Peizong; Teng, Fangfang; Song, Zhimei

    2016-01-01

    Core-shell structured aggregates of amphiphilic block copolymer are hopefully drug delivery system because of their ability to encapsulate hydrophobic drugs, and their hydrophilic shell can prolong retention time of drugs in the blood circulation system. Cyclodextrin is a kind of hydrophilic polysaccharide containing multiple hydroxyl groups, providing an inner hole that can load small molecule through host-guest interaction. These hydroxyl groups or their derived functional ones are utilized in conjugation with polymeric chains to form block copolymers. These copolymers can not only encapsulate hydrophobic drugs, but also encapsulate hydrophilic drugs (like DNA, protein, etc) through hydrophobic, host-guest or electrostatic interactions, which strengthen interaction between drugs and materials compared with general copolymers, indicating that formed drug delivery systems are more stable. By introduction of target molecule, they also achieve selective delivery of drugs to specific tissues or organs. So, several researchers are stimulated to carry out many studies for the development of cyclodextrin copolymeric drug delivery systems in recent. In this review, we focus the cyclodextrin copolymers' application in the anticancer agents' delivery. PMID:26349814

  10. Repurposing Drugs in Oncology (ReDO)—diclofenac as an anti-cancer agent

    Science.gov (United States)

    Pantziarka, Pan; Sukhatme, Vidula; Bouche, Gauthier; Meheus, Lydie; Sukhatme, Vikas P

    2016-01-01

    Diclofenac (DCF) is a well-known and widely used non-steroidal anti-inflammatory drug (NSAID), with a range of actions which are of interest in an oncological context. While there has long been an interest in the use of NSAIDs in chemoprevention, there is now emerging evidence that such drugs may have activity in a treatment setting. DCF, which is a potent inhibitor of COX-2 and prostaglandin E2 synthesis, displays a range of effects on the immune system, the angiogenic cascade, chemo- and radio-sensitivity and tumour metabolism. Both pre-clinical and clinical evidence of these effects, in multiple cancer types, is assessed and summarised and relevant mechanisms of action outlined. Based on this evidence the case is made for further clinical investigation of the anticancer effects of DCF, particularly in combination with other agents - with a range of possible multi-drug and multi-modality combinations outlined in the supplementary materials accompanying the main paper. PMID:26823679

  11. Repurposing Drugs in Oncology (ReDO)-diclofenac as an anti-cancer agent.

    Science.gov (United States)

    Pantziarka, Pan; Sukhatme, Vidula; Bouche, Gauthier; Meheus, Lydie; Sukhatme, Vikas P

    2016-01-01

    Diclofenac (DCF) is a well-known and widely used non-steroidal anti-inflammatory drug (NSAID), with a range of actions which are of interest in an oncological context. While there has long been an interest in the use of NSAIDs in chemoprevention, there is now emerging evidence that such drugs may have activity in a treatment setting. DCF, which is a potent inhibitor of COX-2 and prostaglandin E2 synthesis, displays a range of effects on the immune system, the angiogenic cascade, chemo- and radio-sensitivity and tumour metabolism. Both pre-clinical and clinical evidence of these effects, in multiple cancer types, is assessed and summarised and relevant mechanisms of action outlined. Based on this evidence the case is made for further clinical investigation of the anticancer effects of DCF, particularly in combination with other agents - with a range of possible multi-drug and multi-modality combinations outlined in the supplementary materials accompanying the main paper. PMID:26823679

  12. Microencapsulation of lectin anti-cancer agent and controlled release by alginate beads, biosafety approach.

    Science.gov (United States)

    El-Aassar, M R; Hafez, Elsayed E; El-Deeb, Nehal M; Fouda, Moustafa M G

    2014-08-01

    Hepatocellular carcinoma (HCC) is considered as one of the most aggressive cancer worldwide. In Egypt, the prevalence of HCC is increasing during last years. Recently, drug-loaded microparticles were used to improve the efficiency of various medical treatments. This study is designed to evaluate the anticancer potentialities of lectins against HCC while hinting to its safety usage. The aim is also extended to encapsulate lectins in alginate microbeads for oral drug delivery purposes. The extracted lectins showed anti-proliferative effect against HCC with a percentage of 60.76% by using its nontoxic dose with an up-regulation of P53 gene expression. Concerning the handling of lectin alginate microbeads for oral drug delivery, the prepared lectin alginate beads were ∼100μm in diameter. The efficiency of the microcapsules was checked by scanning electron microscopy, the SEM showed the change on the alginate beads surface revealing the successful lectin encapsulation. The release of lectins from the microbeads depended on a variety of factors as the microbeads forming carriers and the amount-encapsulated lectins. The Pisum sativum extracted lectins may be considered as a promising agent in controlling HCC and this solid dosage form could be suitable for oral administration complemented with/or without the standard HCC drugs. PMID:24857870

  13. Synthesis and biological evaluation of new naphthalene substituted thiosemicarbazone derivatives as potent antifungal and anticancer agents.

    Science.gov (United States)

    Altıntop, Mehlika Dilek; Atlı, Özlem; Ilgın, Sinem; Demirel, Rasime; Özdemir, Ahmet; Kaplancıklı, Zafer Asım

    2016-01-27

    New thiosemicarbazone derivatives (1-10) were obtained via the reaction of 4-(naphthalen-1-yl)thiosemicarbazide with fluoro-substituted aromatic aldehydes. The synthesized compounds were evaluated for their in vitro antifungal effects against pathogenic yeasts and molds using broth microdilution assay. Ames and umuC assays were carried out to determine the genotoxicity of the most effective antifungal derivatives. Furthermore, all compounds were evaluated for their cytotoxic effects on A549 human lung adenocarcinoma and NIH/3T3 mouse embryonic fibroblast cell lines using XTT test. Among these derivatives, 4-(naphthalen-1-yl)-1-(2,3-difluorobenzylidene)thiosemicarbazide (1) and 4-(naphthalen-1-yl)-1-(2,5-difluorobenzylidene)thiosemicarbazide (3) can be identified as the most promising antifungal derivatives due to their notable inhibitory effects on Candida species and no cytotoxicity against NIH/3T3 mouse embryonic fibroblast cell line. According to Ames and umuC assays, compounds 1 and 3 were classified as non-mutagenic compounds. On the other hand, 4-(naphthalen-1-yl)-1-(2,4-difluorobenzylidene)thiosemicarbazide (2) can be considered as the most promising anticancer agent against A549 cell line owing to its notable inhibitory effect on A549 cells with an IC50 value of 31.25 μg/mL when compared with cisplatin (IC50 = 16.28 μg/mL) and no cytotoxicity against NIH/3T3 cells. PMID:26706351

  14. Bridging academic science and clinical research in the search for novel targeted anti-cancer agents

    Institute of Scientific and Technical Information of China (English)

    Alex Matter

    2015-01-01

    This review starts with a brief history of drug discovery&development, and the place of Asia in this worldwide effort discussed. hTe conditions and constraints of a successful translational R&D involving academic basic research and clinical research are discussed and the Singapore model for pursuit of open R&D described. hTe importance of well-characterized, validated drug targets for the search for novel targeted anti-cancer agents is emphasized, as well as a structured, high quality translational R&D. Furthermore, the characteristics of an attractive preclinical development drug candidate are discussed laying the foundation of a successful preclinical development. hTe most frequent sources of failures are described and risk management at every stage is highly recommended. Organizational factors are also considered to play an important role. hTe factors to consider before starting a new drug discovery&development project are described, and an example is given of a successful clinical project that has had its roots in local universities and was carried through preclinical development into phase I clinical trials.

  15. Recent developments in l-asparaginase discovery and its potential as anticancer agent.

    Science.gov (United States)

    Shrivastava, Abhinav; Khan, Abdul Arif; Khurshid, Mohsin; Kalam, Mohd Abul; Jain, Sudhir K; Singhal, Pradeep K

    2016-04-01

    l-Asparaginase (EC3.5.1.1) is an enzyme, which is used for treatment of acute lymphoblastic leukaemia (ALL) and other related blood cancers from a long time. This enzyme selectively hydrolyzes the extracellular amino acid l-asparagine into l-aspartate and ammonia, leading to nutritional deficiencies, protein synthesis inhibition, and ultimately death of lymphoblastic cells by apoptosis. Currently, bacterial asparaginases are used for treatment purpose but offers scepticism due to a number of toxicities, including thrombosis, pancreatitis, hyperglycemia, and hepatotoxicity. Resistance towards bacterial asparaginase is another major disadvantage during cancer management. This situation attracted attention of researchers towards alternative sources of l-asparaginase, including plants and fungi. Present article discusses about potential of l-asparaginase as an anticancer agent, its mechanism of action, and adverse effects related to current asparaginase formulations. This article also provides an outlook for recent developments in l-asparaginase discovery from alternative sources and their potential as a less toxic alternative to current formulations. PMID:25630663

  16. Structure-activity relationships of novel substituted naphthalene diimides as anticancer agents.

    Science.gov (United States)

    Milelli, Andrea; Tumiatti, Vincenzo; Micco, Marialuisa; Rosini, Michela; Zuccari, Guendalina; Raffaghello, Lizzia; Bianchi, Giovanna; Pistoia, Vito; Fernando Díaz, J; Pera, Benet; Trigili, Chiara; Barasoain, Isabel; Musetti, Caterina; Toniolo, Marianna; Sissi, Claudia; Alcaro, Stefano; Moraca, Federica; Zini, Maddalena; Stefanelli, Claudio; Minarini, Anna

    2012-11-01

    Novel 1,4,5,8-naphthalenetetracarboxylic diimide (NDI) derivatives were synthesized and evaluated for their antiproliferative activity on a wide number of different tumor cell lines. The prototypes of the present series were derivatives 1 and 2 characterized by interesting biological profiles as anticancer agents. The present investigation expands on the study of structure-activity relationships of prototypes 1 and 2, namely, the influence of the different substituents of the phenyl rings on the biological activity. Derivatives 3-22, characterized by a different substituent on the aromatic rings and/or a different chain length varying from two to three carbon units, were synthesized and evaluated for their cytostatic and cytotoxic activities. The most interesting compound was 20, characterized by a linker of three methylene units and a 2,3,4-trimethoxy substituent on the two aromatic rings. It displayed antiproliferative activity in the submicromolar range, especially against some different cell lines, the ability to inhibit Taq polymerase and telomerase, to trigger caspase activation by a possible oxidative mechanism, to downregulate ERK 2 protein and to inhibit ERKs phosphorylation, without acting directly on microtubules and tubuline. Its theoretical recognition against duplex and quadruplex DNA structures have been compared to experimental thermodynamic measurements and by molecular modeling investigation leading to putative binding modes. Taken together these findings contribute to define this compound as potential Multitarget-Directed Ligands interacting simultaneously with different biological targets. PMID:22819507

  17. Synthesis and screening of ursolic acid-benzylidine derivatives as potential anti-cancer agents.

    Science.gov (United States)

    Dar, Bilal Ahmad; Lone, Ali Mohd; Shah, Wajaht Amin; Qurishi, Mushtaq Ahmad

    2016-03-23

    Ursolic acid present abundantly in plant kingdom is a well-known compound with various promising biological activities including, anti-cancer, anti-inflammatory, hepatoprotective, antiallergic and anti-HIV properties. Herein, a library of ursolic acid-benzylidine derivatives have been designed and synthesized using Claisen Schmidt condensation of ursolic acid with various aromatic aldehydes in an attempt to develop potent antitumor agents. The compounds were evaluated against a panel of four human carcinoma cell lines including, A-549 (lung), MCF-7 (breast), HCT-116 (colon), THP-1 (leukemia) and a normal human epithelial cell line (FR-2). The results from MTT assay revealed that all the compounds displayed high level of antitumor activities compared with the triazole analogs (previously reported) and the parent ursolic acid. However, compound 3b, the most active derivative was subjected to mechanistic studies to understand the underlying mechanism. The results revealed that compound 3b induced apoptosis in HCT-116 cell lines, arrest cell cycle in the G1 phase, caused accumulation of cytochrome c in the cytosol and increased the expression levels of caspase-9 and caspase-3 proteins. Therefore, compound 3b induces apoptosis in HCT-116 cells through mitochondrial pathway. PMID:26854375

  18. Anticancer activity of Ophiobolin A, isolated from the endophytic fungus Bipolaris setariae.

    Science.gov (United States)

    Bhatia, Dimple R; Dhar, Payal; Mutalik, Varun; Deshmukh, Sunil Kumar; Verekar, Shilpa A; Desai, Dattatraya C; Kshirsagar, Rajendra; Thiagarajan, Padma; Agarwal, Veena

    2016-06-01

    The present work describes the anticancer activity of Ophiobolin A isolated from the endophytic fungus Bipolaris setariae. Ophiobolin A was isolated using preparative HPLC and its structure was confirmed by HRMS, (1)H NMR, (13)C NMR, COSY, DEPT, HSQC and HMBC. It inhibited solid and haematological cancer cell proliferation with IC50 of 0.4-4.3 μM. In comparison, IC50 against normal cells was 20.9 μM. It was found to inhibit the phosphorylation of S6 (IC50 = 1.9 ± 0.2 μM), ERK (IC50 = 0.28 ± 0.02 μM) and RB (IC50 = 1.42 ± 0.1 μM), the effector proteins of PI3K/mTOR, Ras/Raf/ERK and CDK/RB pathways, respectively. It induced apoptosis and inhibited cell cycle progression in MDA-MB-231 cancer cells with concomitant inhibition of signalling proteins. Thus, this study reveals that anticancer activity of Ophiobolin A is associated with simultaneous inhibition of multiple oncogenic signalling pathways namely PI3K/mTOR, Ras/Raf/ERK and CDK/RB. PMID:26212208

  19. Bio-assay Guided Isolation of Anti-cancer Compounds from Anthocephalus cadamba Bark.

    Science.gov (United States)

    Kumar, Deepak; Tejaswi, Chilukuri; Rasamalla, Saiprasanna; Mallick, Sumana; Pala, Bikas C

    2015-08-01

    Anthocephalus cadamba, an important plant in the traditional system of medicine in India, is reported to possess anticancer activity. Guided by bio-assay tests using human colorectal (HCT116) and hepatocellular carcinoma (HepG2) cell lines, it has been shown to contain three active constituents, the triterpenoid saponins 3-O-[α-L-rhamnopyranosyl]-quinovic acid (1) and 3-O-[α-L-rhamnopyranosyl]-quinovic acid 28-O-[β-D-glucopyranosyl] ester (2), and the alkaloid cadambine (3). The structures of the isolated compounds were established using spectroscopic techniques. The isolated compounds demonstrated concentration dependent inhibition of both the cell lines, where compound 3 proved to be the most potent inhibitor of cell line HCT116 (IC50 45 +/- 4 μg/mL) and compound 2 demonstrated maximum inhibitory activity against HepG2 cell line with an IC50 value of 89 +/- 7 μg/mL. PMID:26434112

  20. Synthesis and evaluation of naphthalene-based thiosemicarbazone derivatives as new anticancer agents against LNCaP prostate cancer cells.

    Science.gov (United States)

    Altintop, Mehlika Dilek; Sever, Belgin; Özdemir, Ahmet; Kuş, Gökhan; Oztopcu-Vatan, Pinar; Kabadere, Selda; Kaplancikli, Zafer Asim

    2016-06-01

    Fourteen new naphthalene-based thiosemicarbazone derivatives were designed as anticancer agents against LNCaP human prostate cancer cells and synthesized. MTT assay indicated that compounds 6, 8 and 11 exhibited inhibitory effect on LNCaP cells. Among these compounds, 4-(naphthalen-1-yl)-1-[1-(4-hydroxyphenyl)ethylidene)thiosemicarbazide (6), which caused more than 50% death on LNCaP cells, was chosen for flow cytometric analysis of apoptosis. Flow cytometric analysis pointed out that compound 6 also showed apoptotic effect on LNCaP cells. Compound 6 can be considered as a promising anticancer agent against LNCaP cells owing to its potent cytotoxic activity and apoptotic effect. PMID:25826149

  1. Immune mechanisms regulating pharmacokinetics and pharmacodynamics of PEGylated liposomal anticancer agents

    Science.gov (United States)

    Song, Gina

    integrated approaches, we were able to identify the immunological mechanisms at the molecular, tissue, and clinical levels that may contribute to inter-individual variability in PK and PD of PLD. This dissertation research has a potential to make an impact on development of future NP-based anticancer therapeutics as well as on clinical use of PLD (DoxilRTM) and other PEGylated liposomal anticancer agents.

  2. Novel glyoxalase-I inhibitors possessing a “zinc-binding feature” as potential anticancer agents

    Directory of Open Access Journals (Sweden)

    Al-Balas QA

    2016-08-01

    Full Text Available Qosay A Al-Balas,1 Mohammad A Hassan,1 Nizar A Al-Shar’i,1 Nizar M Mhaidat,2 Ammar M Almaaytah,3 Fatima M Al-Mahasneh,1 Israa H Isawi1 1Department of Medicinal Chemistry and Pharmacognosy, 2Department of Clinical Pharmacy, 3Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan Background: The glyoxalase system including two thiol-dependent enzymes, glyoxalase I (Glo-I and glyoxalase II, plays an important role in a ubiquitous metabolic pathway involved in cellular detoxification of cytotoxic 2-oxoaldehydes. Tumor cells have high glycolytic activity, leading to increased cellular levels of these toxic metabolites. The increased activity of the detoxification system in cancerous cells makes this pathway a viable target for developing novel anticancer agents. In this study, we examined the potential utility of non-glutathione-based inhibitors of the Glo-I enzyme as novel anticancer drugs.Methods: Computer-aided drug design techniques, such as customized pharmacophoric features, virtual screening, and flexible docking, were used to achieve the project goals. Retrieved hits were extensively filtered and subsequently docked into the active site of the enzyme. The biological activities of retrieved hits were assessed using an in vitro assay against Glo-I.Results: Since Glo-I is a zinc metalloenzyme, a customized Zn-binding pharmacophoric feature was used to search for selective inhibitors via virtual screening of a small-molecule database. Seven hits were selected, purchased, and biologically evaluated. Three of the seven hits inhibited Glo-I activity, the most effective of which exerted 76.4% inhibition at a concentration of 25 µM.Conclusion: We successfully identified a potential Glo-I inhibitor that can serve as a lead compound for further optimization. Moreover, our in silico and experimental results were highly correlated. Hence, the docking protocol adopted in this study may

  3. Assessment of Performance of Manufacturing Procedures in a Unit for Production of Investigational Anticancer Agents, Using a Mixed Effects Analysis

    OpenAIRE

    van der Schoot, S. C.; Nuijen, B; Huitema, A D R; Beijnen, J.H.

    2007-01-01

    Purpose To identify the magnitude and sources of variability of a generic, aseptic manufacturing process for experimental anticancer agents employed at our facility, and to estimate the effects on product quality. Materials and Methods In-process and quality control data of all products manufactured according to this generic process (composed of weighing, dissolution, filtration, filling, semi-stoppering and lyophilization) over a 3-year period were retrospectively analyzed using mixed-effect...

  4. Anticancer Properties of Lamellarins

    OpenAIRE

    Christian Bailly

    2015-01-01

    In 1985 the first lamellarins were isolated from a small oceanic sea snail. Today, more than 50 lamellarins have been inventoried and numerous derivatives synthesized and tested as antiviral or anticancer agents. The lead compound in the family is lamellarin D, characterized as a potent inhibitor of both nuclear and mitochondrial topoisomerase I but also capable of directly interfering with mitochondria to trigger cancer cell death. The pharmacology and chemistry of lamellarins are discussed ...

  5. Novel quinolines carrying pyridine, thienopyridine, isoquinoline, thiazolidine, thiazole and thiophene moieties as potential anticancer agents.

    Science.gov (United States)

    Ghorab, Mostafa M; Alsaid, Mansour S; Al-Dosari, Mohammed S; Ragab, Fatma A; Al-Mishari, Abdullah A; Almoqbil, Abdulaziz N

    2016-06-01

    As a part of ongoing studies in developing new anticancer agents, novel 1,2-dihydropyridine 4, thienopyridine 5, isoquinolines 6-20, acrylamide 21, thiazolidine 22, thiazoles 23-29 and thiophenes 33-35 bearing a biologically active quinoline nucleus were synthesized. The structure of newly synthesized compounds was confirmed on the basis of elemental analyses and spectral data. All the newly synthesized compounds were evaluated for their cytotoxic activity against the breast cancer cell line MCF7. 2,3-Dihydrothiazole-5-carboxamides 27, 25, 4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (34), 1,2-dihydroisoquinoline-7-carbonitrile (7), 5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide (35), 1,2-dihydroisoquinoline-7-carbonitrile (6), 2-cyano-3-(dimethylamino)-N-(quinolin-3-yl)acrylamide (21), 1,2-dihydroisoquinoline-7-carbonitriles (11) and (8) exhibited higher activity (IC50 values of 27-45 μmol L-1) compared to doxorubicin (IC50 47.9 μmol L-1). LQ quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (12), 2-thioxo-2,3-dihydrothiazole-5-carboxamide (28) and quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (15) show activity comparable to doxorubicin, while (quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (9), 2,3-dihydrothiazole-5-carboxamide (24), thieno [3,4-c] pyridine-4(5H)-one (5), cyclopenta[b]thiophene-3-carboxamide (33) and (quinolin-3-yl)-6-stryl-1,2-dihydroisoquinoline-7-carbonitrile (10) exhibited moderate activity, lower than doxorubicin. PMID:27279061

  6. Novel quinolines carrying pyridine, thienopyridine, isoquinoline, thiazolidine, thiazole and thiophene moieties as potential anticancer agents

    Directory of Open Access Journals (Sweden)

    Ghorab Mostafa M.

    2016-06-01

    Full Text Available As a part of ongoing studies in developing new anticancer agents, novel 1,2-dihydropyridine 4, thienopyridine 5, isoquinolines 6–20, acrylamide 21, thiazolidine 22, thiazoles 23–29 and thiophenes 33–35 bearing a biologically active quinoline nucleus were synthesized. The structure of newly synthesized compounds was confirmed on the basis of elemental analyses and spectral data. All the newly synthesized compounds were evaluated for their cytotoxic activity against the breast cancer cell line MCF7. 2,3-Dihydrothiazole-5-carboxamides 27, 25, 4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (34, 1,2-dihydroisoquinoline-7-carbonitrile (7, 5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide (35, 1,2-dihydroisoquinoline-7-carbonitrile (6, 2-cyano-3-(dimethylamino-N-(quinolin-3-ylacrylamide (21, 1,2-dihydroisoquinoline-7-carbonitriles (11 and (8 exhibited higher activity (IC50 values of 27–45 μmol L–1 compared to doxorubicin (IC50 47.9 μmol L–1. LQ quinolin-3-yl-1,2-dihydroisoquinoline-7-carbonitrile (12, 2-thioxo-2,3-dihydrothiazole-5-carboxamide (28 and quinolin-3-yl-1,2-dihydroisoquinoline-7-carbonitrile (15 show activity comparable to doxorubicin, while (quinolin-3-yl-1,2-dihydroisoquinoline-7-carbonitrile (9, 2,3-dihydrothiazole-5-carboxamide (24, thieno [3,4-c] pyridine-4(5H-one (5, cyclopenta[b]thiophene-3-carboxamide (33 and (quinolin-3-yl-6-stryl-1,2-dihydroisoquinoline-7-carbonitrile (10 exhibited moderate activity, lower than doxorubicin.

  7. Clastogenicity Potential Screening of Pleurotus pulmonarius and Pleurotus ostreatus Metabolites as Potential Anticancer and Antileukaemic Agents Using Micronucleus Assay

    Directory of Open Access Journals (Sweden)

    E.O. Akanni

    2010-11-01

    Full Text Available Development of anticancer agents that will selectively destroy cancer cells without injury to normal cells has led to the discovery of novel immunotherapeutic agents such as Pleurotus pulmonarius and Pleurotus ostreatus metabolites. This study is to screen the agents of dreadful side effects of causing mutation after a prolonged use. Clastogenicity potential of the novel anti-cancer and antileukaemic agents Pleurotus pulmonarius and Pleurotus ostreatus metabolites was evaluated in this study. Wister rats were grouped into four with the test groups inoculated intraperitoneally at doses 64 and 16 mg/kg as 12.8 and 3.2% of the LD50 into the high and low dose rat groups respectively with each metabolite in a separate experiment. The treated rats were sacrificed after 24, 48 and 72 h post treatment. Cyclophosphamide (clastogen was inoculated into the positive control group at doses 112 and 28 mg/kg w hile saline was used for the negative control group. In all the treatment groups, only the rats in the positive control group formed micronuclei in their bone marrow cells. There was only an increase in the formation of normochromatic and polychromatic erythrocytes in rat groups inoculated with Pleurotus ostreatus metabolites. There is no statistically significant difference (p>0.05 between the 3 post treatment sacrificing periods. Similar result was also obtained for Pleurotus pulmonarius group. The chromosomal damaging potential screening reveals that the Pleurotus ostreatus and Pleurotus pulmonarius metabolites are not clastogenic (genotoxic that is, unlikely to cause cancer producing mutations, but rather enhanced erythropoiesis. They could therefore be useful anticancer agents when the potential is fully explored.

  8. Cyclooxygenase-2 inhibitor is a robust enhancer of anticancer agents against hepatocellular carcinoma multicellular spheroids

    Directory of Open Access Journals (Sweden)

    Cui J

    2014-02-01

    Full Text Available Jie Cui,1,2 Ya-Huan Guo,3 Hong-Yi Zhang,4 Li-Li Jiang,1 Jie-Qun Ma,1 Wen-Juan Wang,1 Min-Cong Wang,1 Cheng-Cheng Yang,1 Ke-Jun Nan,1 Li-Ping Song5 1Department of Oncology, First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an, 2Department of Oncology, Yan'an University Affiliated Hospital, Yan'an, 3Department of Oncology, Shaanxi Province Cancer Hospital, Xi'an, 4Department of Urology, Yan'an University Affiliated Hospital, Yan'an, 5Department of Radiotherapy, First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an, People's Republic of China Purpose: Celecoxib, an inhibitor of cyclooxygenase-2 (COX2, was investigated for enhancement of chemotherapeutic efficacy in cancer clinical trials. This study aimed to determine whether celecoxib combined with 5-fluorouracil or sorafenib or gefitinib is beneficial in HepG2 multicellular spheroids (MCSs, as well as elucidate the underlying mechanisms. Methods: The human hepatocellular carcinoma cell line HepG2 MCSs were used as in vitro models to investigate the effects of celecoxib combined with 5-fluorouracil or sorafenib or gefitinib treatment on cell growth, apoptosis, and signaling pathway. Results: MCSs showed resistance to drugs compared with monolayer cells. Celecoxib combined with 5-fluorouracil or sorafenib exhibited a synergistic action. Exposure to celecoxib (21.8 µmol/L plus 5-fluorouracil (8.1 × 10-3 g/L or sorafenib (4.4 µmol/L increased apoptosis but exerted no effect on COX2, phosphorylated epidermal growth-factor receptor (p-EGFR and phosphorylated (p-AKT expression. Gefitinib (5 µmol/L, which exhibits no growth-inhibition activity as a single agent, increased the inhibitory effect of celecoxib. Gefitinib (5 µmol/L plus celecoxib (21.8 µmol/L increased apoptosis. COX2, p-EGFR, and p-AKT were inhibited. Conclusion: Celecoxib combined with 5-fluorouracil or sorafenib or gefitinib may be superior to single-agent therapy in HepG2

  9. The prince and the pauper. A tale of anticancer targeted agents.

    Science.gov (United States)

    Dueñas-González, Alfonso; García-López, Patricia; Herrera, Luis Alonso; Medina-Franco, Jose Luis; González-Fierro, Aurora; Candelaria, Myrna

    2008-01-01

    Cancer rates are set to increase at an alarming rate, from 10 million new cases globally in 2000 to 15 million in 2020. Regarding the pharmacological treatment of cancer, we currently are in the interphase of two treatment eras. The so-called pregenomic therapy which names the traditional cancer drugs, mainly cytotoxic drug types, and post-genomic era-type drugs referring to rationally-based designed. Although there are successful examples of this newer drug discovery approach, most target-specific agents only provide small gains in symptom control and/or survival, whereas others have consistently failed in the clinical testing. There is however, a characteristic shared by these agents: -their high cost-. This is expected as drug discovery and development is generally carried out within the commercial rather than the academic realm. Given the extraordinarily high therapeutic drug discovery-associated costs and risks, it is highly unlikely that any single public-sector research group will see a novel chemical "probe" become a "drug". An alternative drug development strategy is the exploitation of established drugs that have already been approved for treatment of non-cancerous diseases and whose cancer target has already been discovered. This strategy is also denominated drug repositioning, drug repurposing, or indication switch. Although traditionally development of these drugs was unlikely to be pursued by Big Pharma due to their limited commercial value, biopharmaceutical companies attempting to increase productivity at present are pursuing drug repositioning. More and more companies are scanning the existing pharmacopoeia for repositioning candidates, and the number of repositioning success stories is increasing. Here we provide noteworthy examples of known drugs whose potential anticancer activities have been highlighted, to encourage further research on these known drugs as a means to foster their translation into clinical trials utilizing the more limited

  10. The prince and the pauper. A tale of anticancer targeted agents

    Directory of Open Access Journals (Sweden)

    González-Fierro Aurora

    2008-10-01

    Full Text Available Abstract Cancer rates are set to increase at an alarming rate, from 10 million new cases globally in 2000 to 15 million in 2020. Regarding the pharmacological treatment of cancer, we currently are in the interphase of two treatment eras. The so-called pregenomic therapy which names the traditional cancer drugs, mainly cytotoxic drug types, and post-genomic era-type drugs referring to rationally-based designed. Although there are successful examples of this newer drug discovery approach, most target-specific agents only provide small gains in symptom control and/or survival, whereas others have consistently failed in the clinical testing. There is however, a characteristic shared by these agents: -their high cost-. This is expected as drug discovery and development is generally carried out within the commercial rather than the academic realm. Given the extraordinarily high therapeutic drug discovery-associated costs and risks, it is highly unlikely that any single public-sector research group will see a novel chemical "probe" become a "drug". An alternative drug development strategy is the exploitation of established drugs that have already been approved for treatment of non-cancerous diseases and whose cancer target has already been discovered. This strategy is also denominated drug repositioning, drug repurposing, or indication switch. Although traditionally development of these drugs was unlikely to be pursued by Big Pharma due to their limited commercial value, biopharmaceutical companies attempting to increase productivity at present are pursuing drug repositioning. More and more companies are scanning the existing pharmacopoeia for repositioning candidates, and the number of repositioning success stories is increasing. Here we provide noteworthy examples of known drugs whose potential anticancer activities have been highlighted, to encourage further research on these known drugs as a means to foster their translation into clinical trials

  11. Design and Synthesis of 3-Substituedmethylenethiochroman-4-ones as Anticancer Agents

    Institute of Scientific and Technical Information of China (English)

    MA Zheng-yue; ZHANG Xing-hua; LI Chun-na; ZHENG Ya-jun; YANG Geng-liang; WANG Shi-kui; HE Yang

    2011-01-01

    A series of 3-substituedmethylenethiochroman-4-ones was designed and synthesized,and their structures were confirmed by 1H NMR,13C NMR,MS,IR,UV and elemental analysis.The results of their anticancer activity studies show that almost all 3-chloromethylenethiochroman-4-ones exhibit high anticancer activities and their activities are all better than reference cisplatin.Their IC50 against cancer cells is in a range of 0.80-9.17 μg/mL.Thus they could be promising candidates for anticancer drugs.However,compound 5 has no activity against cancer cells,thus chloromethylene at the 3 position of thiochroman-4-ones seems to play an important role in observed anticancer activities.

  12. Can Some Marine-Derived Fungal Metabolites Become Actual Anticancer Agents?

    OpenAIRE

    Gomes, Nelson G. M.; Florence Lefranc; Anake Kijjoa; Robert Kiss

    2015-01-01

    Marine fungi are known to produce structurally unique secondary metabolites, and more than 1000 marine fungal-derived metabolites have already been reported. Despite the absence of marine fungal-derived metabolites in the current clinical pipeline, dozens of them have been classified as potential chemotherapy candidates because of their anticancer activity. Over the last decade, several comprehensive reviews have covered the potential anticancer activity of marine fungal-derived metabolites. ...

  13. Adding pharmacogenomics to the development of new marine-derived anticancer agents

    OpenAIRE

    Aracil Miguel; Jimeno José; Tercero Juan

    2006-01-01

    Abstract Nature has always been a highly productive tool in the development of anticancer therapies. Renewed interest in the potential of this tool has recently been sparked by the realization that the marine ecosystem can be used for the discovery and development of new compounds with clinical potential in advanced resistant tumors. These compounds can be incorporated into combination approaches in a chronic therapy scenario. Our marine anticancer program is using the sea to develop new agen...

  14. Immune cell-based screening assay for response to anticancer agents: applications in pharmacogenomics

    Directory of Open Access Journals (Sweden)

    Frick A

    2015-02-01

    Full Text Available Amber Frick,1 Yuri Fedoriw,2 Kristy Richards,3,4 Blossom Damania,3,5 Bethany Parks,6 Oscar Suzuki,1 Cristina S Benton,1 Emmanuel Chan,1 Russell S Thomas,7 Tim Wiltshire1,3 1Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, 2Department of Pathology and Laboratory Medicine, School of Medicine, 3Lineberger Comprehensive Cancer Center, School of Medicine, 4Department of Genetics, School of Medicine, 5Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA; 6The Hamner Institutes for Health Sciences, 7Environmental Protection Agency, Research Triangle Park, NC, USA Background: Interpatient variability in immune and chemotherapeutic cytotoxic responses is likely due to complex genetic differences and is difficult to ascertain in humans. Through the use of a panel of genetically diverse mouse inbred strains, we developed a drug screening platform aimed at examining interstrain differences in viability on normal, noncancerous immune cells following chemotherapeutic cytotoxic insult. Drug effects were investigated by comparing selective chemotherapeutic agents, such as BEZ-235 and selumetinib, against conventional cytotoxic agents targeting multiple pathways, including doxorubicin and idarubicin. Methods: Splenocytes were isolated from 36 isogenic strains of mice using standard procedures. Of note, the splenocytes were not stimulated to avoid attributing responses to pathways involved with cellular stimulation rather than toxicity. Cells were incubated with compounds on a nine-point logarithmic dosing scale ranging from 15 nM to 100 µM (37°C, 5% CO2. At 4 hours posttreatment, cells were labeled with antibodies and physiological indicator dyes and fixed with 4% paraformaldehyde. Cellular phenotypes (eg, viability were collected and analyzed using flow cytometry. Dose-response curves with response normalized to the zero dose as a function of log concentration

  15. Strigolactone analogs act as new anti-cancer agents in inhibition of breast cancer in xenograft model.

    Science.gov (United States)

    Mayzlish-Gati, Einav; Laufer, Dana; Grivas, Christopher F; Shaknof, Julia; Sananes, Amiram; Bier, Ariel; Ben-Harosh, Shani; Belausov, Eduard; Johnson, Michael D; Artuso, Emma; Levi, Oshrat; Genin, Ola; Prandi, Cristina; Khalaila, Isam; Pines, Mark; Yarden, Ronit I; Kapulnik, Yoram; Koltai, Hinanit

    2015-01-01

    Strigolactones (SLs) are a novel class of plant hormones. Previously, we found that analogs of SLs induce growth arrest and apoptosis in breast cancer cell lines. These compounds also inhibited the growth of breast cancer stem cell enriched-mammospheres with increased potency. Furthermore, strigolactone analogs inhibited growth and survival of colon, lung, prostate, melanoma, osteosarcoma and leukemia cancer cell lines. To further examine the anti-cancer activity of SLs in vivo, we have examined their effects on growth and viability of MDA-MB-231 tumor xenografts model either alone or in combination with paclitaxel. We show that strigolactone act as new anti-cancer agents in inhibition of breast cancer in xenograft model. In addition we show that SLs affect the integrity of the microtubule network and therefore may inhibit the migratory phenotype of the highly invasive breast cancer cell lines that were examined. PMID:26192476

  16. Molecular analysis and anticancer properties of two identified isolates, Fusarium solani and Emericella nidulans isolated from Wady El-Natron soil in Egypt against Caco-2 (ATCC) cell line

    Institute of Scientific and Technical Information of China (English)

    Hala F Mohamed

    2012-01-01

    Objective: To characterize, identify and investigate the anticancer properties of two new soil fungal isolates, Emericella nidulans and Fusarium solani isolated from Wady El-Natron in Egypt against colon cancer Caco-2 (ATCC) cell line. Methods: Soil sample was cultured and two strains were chosen for morphological and phenotypical characterization. Partial sequences of the 18s rRNA gene and the internal transcribed spacer region ITS of the two isolates were amplified by PCR. Phylogenetic tree construction and analysis of the resulted multiple sequences from the two fugal isolates were also carried out. In vitro anticancer activity of the two strains was done against colon Caco-2 cancer cell line. Reverse transcription – PCR was carried out to detect level of expression of p53 in Caco-2 cell line. Results: HF.1 displayed morphological and genotypic characteristics most similar to that of Fusarium solani while HF.2 was most similar to Emericella nidulans with high similarity of 99% and 97% respectively. The multiple sequence alignment of the two fungal isolates showed that, the maximum identical conserved domains in the 18s rRNA genes were identified with the nucleotide regions of 51st to 399th base pairs, 88th to 525th base pairs respectively. While those in the ITS genes were identified with the nucleotide regions of 88th to 463rdand 51st to 274th. The two isolates showed IC50 value with (6.24±5.21) and (9.84±0.36) μg/mL) concentrations respectively at 28h. Reverse transcription – PCR indicated that these cells showed high level of expression for p53 mRNA. Conclusions: The morphology and molecular analysis identified HF.1 and HF.2 to be Fusarium solani and Emericella nidulans; new isolates of anticancer producing fungi from Wady El-Natroon city in Egypt. Treatment with the two isolates caused P53 expression in Caco-2 cell line. These two isolates can be used as an anticancer agents.

  17. Preparing cytotoxic agents in an isolator.

    Science.gov (United States)

    Favier, M; Hansel, S; Bressolle, F

    1993-11-01

    The design of an isolator and its use by an oncology satellite pharmacy for preparing cytotoxic drugs are described. The isolator (Iso Concept, Boulogne, France) is a totally enclosed ventilated biological-safety cabinet of class III polyvinyl chloride (PVC) with positive air pressure, a half-suit with a rotating seal, and attached neoprene gloves. There are three work-stations, one for the half-suit and two along one side of the isolator. The ventilation and air filtration system consists of one entry pipe with a full ventilation-filtration box fitted with one prefilter, one blower, one ball valve, one high-efficiency particulate air (HEPA) filter, one airtight nipple connected to an automatic sterilizer, alarms, and one exhaust pipe protected by a HEPA filter. The air lock consists of a rigid, transparent Plexiglas pass-through. The chamber is sterilized with heated compressed air mixed with 3.5% peracetic acid. Maintenance includes regular changing of gloves and HEPA filters; checking of the integrity of the PVC, half-suit, and gloves; and washing and decontamination procedures. Preparation of cytotoxics is planned in advance with prescription data and manufacturing sheets. In the half-suit, a pharmacy technician reads the label, supervises preparation of the sterile admixture, and writes a label. The operators on the side of the unit read the manufacturing sheet and prepare the dose identified by the label.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8266957

  18. Curcumin-albumin conjugates as an effective anti-cancer agent with immunomodulatory properties.

    Science.gov (United States)

    Aravind, S R; Krishnan, Lissy K

    2016-05-01

    the drug form has the potential to be used as an anticancer agent in affected human subjects. PMID:26927614

  19. Design, synthesis, and anticancer activity of novel berberine derivatives prepared via CuAAC “click” chemistry as potential anticancer agents

    Directory of Open Access Journals (Sweden)

    Jin X

    2014-08-01

    Full Text Available Xin Jin1,2,* Tian-Hua Yan,3,* Lan Yan,1 Qian Li,4 Rui-Lian Wang,1 Zhen-Lin Hu,1 Yuan-Ying Jiang,1 Qing-Yan Sun,1 Yong-Bing Cao1 1School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China; 2School of Pharmacy, FuJian University of Traditional Chinese Medicine, Fuzhou, People's Republic of China; 3Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China; 4Diakite Biological Technology Co., Ltd, Shanghai, People's Republic of China *These authors contributed equally to this work Abstract: A series of novel derivatives of phenyl-substituted berberine triazolyls has been designed and synthesized via copper-catalyzed azide-alkyne cycloaddition click chemistry in an attempt to develop antitumor agents. All of the compounds were evaluated for anticancer activity against a panel of three human cancer cell lines, including MCF-7 (breast, SW-1990 (pancreatic, and SMMC-7721 (liver and the noncancerous human umbilical vein endothelial cell (HUVEC cell lines. The results indicated that most of the compounds displayed notable anticancer activities against the MCF-7 cells compared with berberine. Among these derivatives, compound 16 showed the most potent inhibitory activity against the SW-1990 and SMMC-7721 cell lines, with half-maximal inhibitory concentration (IC50 values of 8.54±1.97 µM and 11.87±1.83 µM, respectively. Compound 36 exhibited the most potent inhibitory activity against the MCF-7 cell line, with an IC50 value of 12.57±1.96 µM. Compound 16 and compound 36 exhibited low cytotoxicity in the HUVEC cell line, with IC50 values of 25.49±3.24 µM and 30.47±3.47 µM. Furthermore, compounds 14, 15, 16, 17, 18, 32, and 36 exhibited much better selectivity than berberine toward the normal cell line HUVEC. Keywords: berberine, anticancer, click chemistry, structure–activity relationship

  20. Design, synthesis and biological activity of piperlongumine derivatives as selective anticancer agents.

    Science.gov (United States)

    Wu, Yuelin; Min, Xiao; Zhuang, Chunlin; Li, Jin; Yu, Zhiliang; Dong, Guoqiang; Yao, Jiangzhong; Wang, Shengzheng; Liu, Yang; Wu, Shanchao; Zhu, Shiping; Sheng, Chunquan; Wei, Yunyang; Zhang, Huojun; Zhang, Wannian; Miao, Zhenyuan

    2014-07-23

    In an effort to expand the structure-activity relationship of the natural anticancer compound piperlongumine, we have prepared sixteen novel piperlongumine derivatives with halogen or morpholine substituents at C2 and alkyl substituents at C7. Most of 2-halogenated piperlongumines showed potent in vitro activity against four cancer cells and modest selectivity for lung normal cells. The highly active anticancer compound 11h exhibited obvious ROS elevation and excellent in vivo antitumor potency with suppressed tumor growth by 48.58% at the dose of 2 mg/kg. The results indicated that halogen substituents as electrophilic group at C2 played an important role in increasing cytotoxicity. PMID:24937186

  1. Design, Synthesis and Biological Evaluation of Novel 5H-Chromenopyridines as Potential Anti-Cancer Agents

    Directory of Open Access Journals (Sweden)

    Souvik Banerjee

    2015-09-01

    Full Text Available A novel series of 5H-chromenopyridines was identified as anticancer agents in our continuing effort to discover and develop new small molecule anti-proliferative agents. Based on our initial lead SP-6-27 compound, we designed and synthesized novel tricyclic 5H-thiochromenopyridine and 5H-chromenopyridine analogs to evaluate the impact of an additional ring, as well as conformational flexibility on cytotoxic activity against human melanoma and glioma cell lines. All of the 5H-thiochromenopyridines have been achieved in good yields (89%–93% using a single-step, three-component cyclization without the need for purification. The 5H-chromenopyridine analog of the potent 5H-thiochromenopyride was obtained in a good yield upon purification. All newly-prepared 5H-thiochromenopyridines showed good to moderate cytotoxicity against three melanoma and two glioma cell lines (3–15 μM. However, the 5H-chromenopyridine analogue that we prepared in our laboratory lost cytotoxic activity. The moderate cytotoxic activity of 5H-thiochromenopyridines shows the promise of developing chromenopyridines as potential anticancer agents.

  2. From METS to malaria: RRx-001, a multi-faceted anticancer agent with activity in cerebral malaria

    OpenAIRE

    Yalçın, Özlem; Oronsky, Bryan; Carvalho, Leonardo J. M.; Kuypers, Frans A.; Scicinski, Jan; Cabrales, Pedro

    2015-01-01

    RESEARCH Open Access From METS to malaria: RRx-001, a multi-faceted anticancer agent with activity in cerebral malaria Ozlem Yalcin1,2, Bryan Oronsky3, Leonardo J. M. Carvalho4,5, Frans A. Kuypers6, Jan Scicinski3 and Pedro Cabrales1* Abstract Background: The survival of malaria parasites, under substantial haem-induced oxidative stress in the red blood cells (RBCs) is dependent on the pentose phosphate pathway (PPP). The PPP is the only source of NADPH in the RBC, ess...

  3. Anticancer effects of fraction isolated from fruiting bodies of Chaga medicinal mushroom, Inonotus obliquus (Pers.:Fr.) Pilát (Aphyllophoromycetideae): in vitro studies.

    Science.gov (United States)

    Lemieszek, Marta Kinga; Langner, Ewa; Kaczor, Józef; Kandefer-Szerszeń, Martyna; Sanecka, Bozena; Mazurkiewicz, Witold; Rzeski, Wojciech

    2011-01-01

    The medicinal mushroom Chaga, Inonotus obliquus (Pers.:Fr.) Pilát (Hymenochaetaceae), has been used in folk medicine in Russia, Poland, and most of the Baltic countries, as a cleansing and disinfecting measure, and as decoctions for stomach diseases, intestinal worms, liver and heart ailments, and cancer treatment. Many reports have been published concerning the health promoting functions of this mushroom, including antibacterial, hepatoprotective, anti-inflammatory, antitumor, and antioxidant activities. The purpose of the present study was evaluation of in vitro anticancer activity of fraction IO4 isolated from I. obliquus. The effect on cell proliferation, motility and viability was assessed in a range of cancer and normal cells. Chaga fraction prepared from dried fruiting bodies was subjected to anticancer evaluation in human lung carcinoma (A549), colon adenocarcinoma (HT-29), and rat glioma (C6) cell cultures. Human skin fibroblasts (HSF), bovine aorta endothelial cells (BAEC), models of rat oligodendrocytes (OLN-93), hepatocytes (Fao), rat astroglia, and mouse neurons (P19) were applied to test toxicity in normal cells. The following methods were applied: tumor cell proliferation (MTT assay and BrdU assay), cytotoxicity (LDH assay), tumor cell motility (wound assay), tumor cell morphology (May-Grünwald-Giemsa staining), and death detection (ELISA). Chaga fraction elicited anticancer effects which were attributed to decreased tumor cell proliferation, motility and morphological changes induction. Of note is the fact that it produced no or low toxicity in tested normal cells. The data presented could open interesting paths for further investigations of fraction IO4 as a potential anticancer agent. PMID:22135889

  4. Evaluation of bishexadecyltrimethyl ammonium palladium tetrachloride based dual functional colloidal carrier as an antimicrobial and anticancer agent.

    Science.gov (United States)

    Kaur, Gurpreet; Kumar, Sandeep; Dilbaghi, Neeraj; Kaur, Baljinder; Kant, Ravi; Guru, Santosh Kumar; Bhushan, Shashi; Jaglan, Sundeep

    2016-04-12

    We have developed a dual function carrier using bishexadecyltrimethyl ammonium palladium tetrachloride, which has anticancer as well as antibacterial activity, using a ligand insertion method with a simple and easy work procedure. The complex is prepared by a simple and cost effective method using hexadecyltrimethyl ammonium chloride and palladium chloride under controlled stoichiometry. Herein, we report the aggregation (self assembly) of the metallosurfactant having palladium as a counter ion, in aqueous medium along with its binding affinity with bovine serum albumin. The palladium surfactant has exhibited excellent antimicrobial efficacy against fungus and bacteria (both Gram-positive and Gram-negative bacteria). Cytotoxicity of palladium surfactant against cancerous (Human leukemia HL-60, pancreatic MIA-Pa-Ca-2 and prostate cancer PC-3) and healthy cells (fR2 human breast epithelial cells) was also evaluated using MTT assay. The present dual functional moiety shows a low IC50 value and has potential to be used as an anticancer agent. Our dual function carrier which itself possesses antimicrobial and anticancer activity represents a simple and effective system and can also be utilized as a drug carrier in the future. PMID:26961498

  5. Isolation, Characterization and Anticancer Potential of Cytotoxic Triterpenes from Betula utilis Bark

    Science.gov (United States)

    Joshi, Pushpa; Pal, Mahesh; Meena, Baleshwar; Upreti, D. K.; Rana, T. S.; Datta, Dipak

    2016-01-01

    Betula utilis, also known as Himalayan silver birch has been used as a traditional medicine for many health ailments like inflammatation, HIV, renal and bladder disorders as well as many cancers from ages. Here, we performed bio-guided fractionation of Betula utilis Bark (BUB), in which it was extracted in methanol and fractionated with hexane, ethyl acetate, chloroform, n-butanol and water. All six fractions were evaluated for their in-vitro anticancer activity in nine different cancer cell lines and ethyl acetate fraction was found to be one of the most potent fractions in terms of inducing cytotoxic activity against various cancer cell lines. By utilizing column chromatography, six triterpenes namely betulin, betulinic acid, lupeol, ursolic acid (UA), oleanolic acid and β-amyrin have been isolated from the ethyl acetate extract of BUB and structures of these compounds were unraveled by spectroscopic methods. β-amyrin and UA were isolated for the first time from Betula utilis. Isolated triterpenes were tested for in-vitro cytotoxic activity against six different cancer cell lines where UA was found to be selective for breast cancer cells over non-tumorigenic breast epithelial cells (MCF 10A). Tumor cell selective apoptotic action of UA was mainly attributed due to the activation of extrinsic apoptosis pathway via up regulation of DR4, DR5 and PARP cleavage in MCF-7 cells over non-tumorigenic MCF-10A cells. Moreover, UA mediated intracellular ROS generation and mitochondrial membrane potential disruption also play a key role for its anti cancer effect. UA also inhibits breast cancer migration. Altogether, we discovered novel source of UA having potent tumor cell specific cytotoxic property, indicating its therapeutic potential against breast cancer. PMID:27453990

  6. Biochemical characterization and molecular dynamic simulation of β-sitosterol as a tubulin-binding anticancer agent.

    Science.gov (United States)

    Mahaddalkar, Tejashree; Suri, Charu; Naik, Pradeep Kumar; Lopus, Manu

    2015-08-01

    Βeta-sitosterol (β-SITO), a phytosterol present in pomegranate, peanut, corn oil, almond, and avocado, has been recognized to offer health benefits and potential clinical uses. β-SITO is orally bioavailable and, as a constituent of edible natural products, is considered to have no undesired side effects. It has also been considered as a potent anticancer agent. However, the molecular mechanism of action of β-SITO as a tubulin-binding anticancer agent and its binding site on tubulin are poorly understood. Using a combination of biochemical analyses and molecular dynamic simulation, we investigated the molecular details of the binding interactions of β-SITO with tubulin. A polymer mass assay comparing the effects of β-SITO and of taxol and vinblastine on tubulin assembly showed that this phytosterol stabilized microtubule assembly in a manner similar to taxol. An 8-anilino-1-naphthalenesulfonic acid assay confirmed the direct interaction of β-SITO with tubulin. Although β-SITO did not show direct binding to the colchicine site on tubulin, it stabilized the colchicine binding. Interestingly, no sulfhydryl groups of tubulin were involved in the binding interaction of β-SITO with tubulin. Based on the results from the biochemical assays, we computationally modeled the binding of β-SITO with tubulin. Using molecular docking followed by molecular dynamic simulations, we found that β-SITO binds tubulin at a novel site (which we call the 'SITO site') adjacent to the colchicine and noscapine sites. Our data suggest that β-SITO is a potent anticancer compound that interferes with microtubule assembly dynamics by binding to a novel site on tubulin. PMID:25912799

  7. Prediction of sensitivity to anticancer agents for patients with advanced or recurrent breast cancer by Tc-99m sestamibi

    International Nuclear Information System (INIS)

    Tc-99m Sestamibi (99mTc-MIBI) is known to be a substrate of P-glycoprotein (P-gp) that effluxes the drugs out of cancer cells. The overexpression of P-gp involved in multidrug resistance phenomenon in patients with advanced or recurrent breast cancers was shown in the plasma membrane of breast cancer cells. In this study, we examined the usefulness of 99mTc-MIBI scintigraphy for the prediction of sensitivity to anticancer agents in 8 cases with advanced or recurrent breast cancer. The retrospective analysis showed that the sensitivity to the chemotherapy could be evaluated in 3 cases by 99mTc-MIBI scintigraphy, but in the other 5 cases 99mTc-MIBI scintigraphy was not eligible for the prediction of sensitivity. Two out of 3 cases showed over 50% in reduction rate of target tumors (PR) with higher accumulation of 99mTc-MIBI, while another case with PD showed lower. These results suggest that the accumulation of 99mTc-MIBI could be associated with the sensitivity to P-gp-related anticancer agents, and that the functional analysis of P-gp by 99mTc-MIBI might be useful for the prediction of responsiveness of chemotherapy in patients with breast cancer. (author)

  8. Photophysical characterization of anticancer drug valrubicin in rHDL nanoparticles and its use as an imaging agent.

    Science.gov (United States)

    Shah, Sunil; Chib, Rahul; Raut, Sangram; Bermudez, Jaclyn; Sabnis, Nirupama; Duggal, Divya; Kimball, Joseph D; Lacko, Andras G; Gryczynski, Zygmunt; Gryczynski, Ignacy

    2016-02-01

    Nanoparticles are target-specific drug delivery agents that are increasingly used in cancer therapy to enhance bioavailability and to reduce off target toxicity of anti-cancer agents. Valrubicin is an anti-cancer drug, currently approved only for vesicular bladder cancer treatment because of its poor water solubility. On the other hand, valrubicin carrying reconstituted high density lipoprotein (rHDL) nanoparticles appear ideally suited for extended applications, including systemic cancer chemotherapy. We determined selected fluorescence properties of the free (unencapsulated) drug vs. valrubicin incorporated into rHDL nanoparticles. We have found that upon encapsulation into rHDL nanoparticles the quantum yield of valrubicin fluorescence increased six fold while its fluorescence lifetime increased about 2 fold. Accordingly, these and potassium iodide (KI) quenching data suggest that upon incorporation, valrubicin is localized deep in the interior of the nanoparticle, inside the lipid matrix. Fluorescence anisotropy of the rHDL valrubicin nanoparticles was also found to be high along with extended rotational correlation time. The fluorescence of valrubicin could also be utilized to assess its distribution upon delivery to prostate cancer (PC3) cells. Overall the fluorescence properties of the rHDL: valrubicin complex reveal valuable novel characteristics of this drug delivery vehicle that may be particularly applicable when used in systemic (intravenous) therapy. PMID:26735001

  9. Urokinase-targeted recombinant bacterial protein toxins-a rationally designed and engineered anticancer agent for cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Yizhen LIU; Shi-Yan LI

    2009-01-01

    Urokinase-targeted recombinant bacterial protein toxins are a sort of rationally designed and engineered anticancer recombinant fusion proteins representing a novel class of agents for cancer therapy.Bacterial protein toxins have long been known as the primary virulence factor(s) for a variety of pathogenic bacteria and are the most powerful human poisons.On the other hand,it has been well documented that urokinase-type plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR),making up the uPA system,are overexpressed in a variety of human tumors and tumor cell lines.The expression of uPA system is highly correlated with tumor invasion and metastasis.To exploit these characteristics in the design of tumor cell-selective cytotoxins,two prominent bacterial protein toxins,i.e.,the diphtheria toxin and anthrax toxin are deliberately engineered through placing a sequence targeted specifically by the uPA system to form anticancer recombinant fusion proteins.These uPA system-targeted bacterial protein toxins are activated selectively on the surface of uPA systemexpressing tumor cells,thereby killing these cells.This article provides a review on the latest progress in the exploitation of these recombinant fusion proteins as potent tumoricidal agents.It is perceptible that the strategies for cancer therapy are being innovated by this novel therapeutic approach.

  10. A SIMPLE METHOD FOR ISOLATION OF SOME BACILLUS STRAINS WITH AN EXPRESSED ANTI-CANCER ACTIVITY

    Directory of Open Access Journals (Sweden)

    Francesco Marotta

    2006-02-01

    Full Text Available ABSTRACT:There is now increasing evidence that probiotic bacteria can provide health benefits to humans. In many areas of medicine (gastroenterology, urology, allergology, oncology and others, these sanative microorganisms may be considered as possible and viable alternatives applicable to patient care. Particularly, we have found that oral administration of Bacillus oligonitrophilus KU-1 cells can be used for treatment and prevention of some tumors. Here we present a simple method for isolation of bacteria with anticancer properties from soil.RESUMEN:Está aumentando la evidencia de que hay bacterias probióticas que pueden proporcionar beneficios saludables a los seres humanos. En muchas áreas de la medicina (gastroenterología, urología, alergología, oncología y otras, estos microorganismos pueden considerarse como alternativas posibles y viables aplicables al cuidado del paciente. Particularmente, nosotros hemos encontrado que la administración oral de células KU-1 Bacillus oligonitrophilus puede ser utilizada para el tratamiento y la prevención de algunos tumores. Aquí presentamos un método simple para aislamiento de suelos, de bacterias con características anticáncer.

  11. [Isolation, identification and anticancer activity of an endophytic fungi from Juglans mandshurica].

    Science.gov (United States)

    Li, Meiya; Wu, Yunwei; Jiang, Fusheng; Yu, Xiangli; Tang, Kexuan; Miao, Zhiqi

    2009-07-01

    The endophytic fungus named FSN006 was isolated from the inner bark of Juglans mandshurica. It grew quickly and formed circular colony on PDA plate. The upper side of the colony was white, while the lower side of the colony and the conditioned medium were light yellow as a result of significant yellow pigment substances were produced and secreted by the fungi. Green elliptic conidia appeared when cultured on CMX plate. Based on the morphology identification and ITS sequence, it was clear that this fungus belonged to the Deuteromycotina, HyPhomycetes, Moniliales, Trichoderma longibrachiatum. The conditioned medium of FSN006 showed a high anti-tumor ability against liver cancer cell-HepG2, and reached its IC50 concentration after being diluted 20 times, while the IC50 concentration of curcumine was(11.49 +/- 0.12) mg x L(-1). In addition, there was preeminent selective inhibiting effect against the normal liver cell strain HL-7702 and its caner counter strain HepG2. The inhibiting effect against strain HL-7702 was only one quarter of that against HepG2 at the concentration of IC50. Therefore, the fermentation of FSN006 may provide a possible way to produce anticancer drug with higher efficiency and lower toxicity. PMID:19873766

  12. Toward discovering new anti-cancer agents targeting topoisomerase IIα: a facile screening strategy adaptable to high throughput platform.

    Directory of Open Access Journals (Sweden)

    Yu-Shih Lin

    Full Text Available Topoisomerases are a family of vital enzymes capable of resolving topological problems in DNA during various genetic processes. Topoisomerase poisons, blocking reunion of cleaved DNA strands and stabilizing enzyme-mediated DNA cleavage complex, are clinically important antineoplastic and anti-microbial agents. However, the rapid rise of drug resistance that impedes the therapeutic efficacy of these life-saving drugs makes the discovering of new lead compounds ever more urgent. We report here a facile high throughput screening system for agents targeting human topoisomerase IIα (Top2α. The assay is based on the measurement of fluorescence anisotropy of a 29 bp fluorophore-labeled oligonucleotide duplex. Since drug-stabilized Top2α-bound DNA has a higher anisotropy compared with free DNA, this assay can work if one can use a dissociating agent to specifically disrupt the enzyme/DNA binary complexes but not the drug-stabilized ternary complexes. Here we demonstrate that NaClO4, a chaotropic agent, serves a critical role in our screening method to differentiate the drug-stabilized enzyme/DNA complexes from those that are not. With this strategy we screened a chemical library of 100,000 compounds and obtained 54 positive hits. We characterized three of them on this list and demonstrated their effects on the Top2α-mediated reactions. Our results suggest that this new screening strategy can be useful in discovering additional candidates of anti-cancer agents.

  13. Hormetic Effect of Berberine Attenuates the Anticancer Activity of Chemotherapeutic Agents

    OpenAIRE

    Jiaolin Bao; Borong Huang; Lidi Zou; Shenghui Chen; Chao Zhang; Yulin Zhang; Meiwan Chen; Jian-Bo Wan; Huanxing Su; Yitao Wang; Chengwei He

    2015-01-01

    Hormesis is a phenomenon of biphasic dose response characterized by exhibiting stimulatory or beneficial effects at low doses and inhibitory or toxic effects at high doses. Increasing numbers of chemicals of various types have been shown to induce apparent hormetic effect on cancer cells. However, the underlying significance and mechanisms remain to be elucidated. Berberine, one of the major active components of Rhizoma coptidis, has been manifested with notable anticancer activities. This st...

  14. New derivatives of vitamin E as nanovectors for poorly soluble drugs and anticancer agents

    OpenAIRE

    Duhem, Nicolas

    2013-01-01

    The aim of this work was to develop novel vitamin E conjugates for the vectorization of active pharmaceutical ingredients through nanotechnologies. The physico-chemical and biological properties of vitamin E derivatives offer multiple advantages in drug delivery like biocompatibility, improvement of drug solubility and anticancer activity. Nanomedicines have shown high potential in drug delivery since (i) they are appropriate to all route of administration, (ii) they may offer better drug bio...

  15. Enhancement of Selectivity of an Organometallic Anticancer Agent by Redox Modulation.

    Science.gov (United States)

    Romero-Canelón, Isolda; Mos, Magdalena; Sadler, Peter J

    2015-10-01

    Combination with redox modulators can potentiate the anticancer activity and maximize the selectivity of organometallic complexes with redox-based mechanisms of action. We show that nontoxic doses of l-buthionine sulfoximine increase the selectivity of organo-Os complex FY26 for human ovarian cancer cells versus normal lung fibroblasts to 63-fold. This increase is not due to changes in the mechanism of action of FY26 but to the decreased response of cancer cells to oxidative stress. PMID:26397305

  16. Structure-activity relationship for Fe(III)-salen-like complexes as potent anticancer agents.

    Science.gov (United States)

    Ghanbari, Zahra; Housaindokht, Mohammad R; Izadyar, Mohammad; Bozorgmehr, Mohammad R; Eshtiagh-Hosseini, Hossein; Bahrami, Ahmad R; Matin, Maryam M; Khoshkholgh, Maliheh Javan

    2014-01-01

    Quantitative structure activity relationship (QSAR) for the anticancer activity of Fe(III)-salen and salen-like complexes was studied. The methods of density function theory (B3LYP/LANL2DZ) were used to optimize the structures. A pool of descriptors was calculated: 1497 theoretical descriptors and quantum-chemical parameters, shielding NMR, and electronic descriptors. The study of structure and activity relationship was performed with multiple linear regression (MLR) and artificial neural network (ANN). In nonlinear method, the adaptive neuro-fuzzy inference system (ANFIS) was applied in order to choose the most effective descriptors. The ANN-ANFIS model with high statistical significance (R (2) train = 0.99, RMSE = 0.138, and Q (2) LOO = 0.82) has better capability to predict the anticancer activity of the new compounds series of this family. Based on this study, anticancer activity of this compound is mainly dependent on the geometrical parameters, position, and the nature of the substituent of salen ligand. PMID:24955417

  17. A translational study "case report" on the small molecule "energy blocker" 3-bromopyruvate (3BP) as a potent anticancer agent: from bench side to bedside.

    Science.gov (United States)

    Ko, Y H; Verhoeven, H A; Lee, M J; Corbin, D J; Vogl, T J; Pedersen, P L

    2012-02-01

    The small alkylating molecule, 3-bromopyruvate (3BP), is a potent and specific anticancer agent. 3BP is different in its action from most currently available chemo-drugs. Thus, 3BP targets cancer cells' energy metabolism, both its high glycolysis ("Warburg Effect") and mitochondrial oxidative phosphorylation. This inhibits/ blocks total energy production leading to a depletion of energy reserves. Moreover, 3BP as an "Energy Blocker", is very rapid in killing such cells. This is in sharp contrast to most commonly used anticancer agents that usually take longer to show a noticeable effect. In addition, 3BP at its effective concentrations that kill cancer cells has little or no effect on normal cells. Therefore, 3BP can be considered a member, perhaps one of the first, of a new class of anticancer agents. Following 3BP's discovery as a novel anticancer agent in vitro in the Year 2000 (Published in Ko et al. Can Lett 173:83-91, 2001), and also as a highly effective and rapid anticancer agent in vivo shortly thereafter (Ko et al. Biochem Biophys Res Commun 324:269-275, 2004), its efficacy as a potent anticancer agent in humans was demonstrated. Here, based on translational research, we report results of a case study in a young adult cancer patient with fibrolamellar hepatocellular carcinoma. Thus, a bench side discovery in the Department of Biological Chemistry at Johns Hopkins University, School of Medicine was taken effectively to bedside treatment at Johann Wolfgang Goethe University Frankfurt/Main Hospital, Germany. The results obtained hold promise for 3BP as a future cancer therapeutic without apparent cyto-toxicity when formulated properly. PMID:22328020

  18. Preclinical Investigations of PM01183 (Lurbinectedin) as a Single Agent or in Combination with Other Anticancer Agents for Clear Cell Carcinoma of the Ovary

    Science.gov (United States)

    Takahashi, Ryoko; Mabuchi, Seiji; Kawano, Mahiru; Sasano, Tomoyuki; Matsumoto, Yuri; Kuroda, Hiromasa; Kozasa, Katsumi; Hashimoto, Kae; Sawada, Kenjiro; Kimura, Tadashi

    2016-01-01

    Objective The objective of this study was to evaluate the antitumor effects of lurbinectedin as a single agent or in combination with existing anticancer agents for clear cell carcinoma (CCC) of the ovary, which is regarded as an aggressive, chemoresistant, histological subtype. Methods Using human ovarian CCC cell lines, the antitumor effects of lurbinectedin, SN-38, doxorubicin, cisplatin, and paclitaxel as single agents were assessed using the MTS assay. Then, the antitumor effects of combination therapies involving lurbinectedin and 1 of the other 4 agents were evaluated using isobologram analysis to examine whether these combinations displayed synergistic effects. The antitumor activity of each treatment was also examined using cisplatin-resistant and paclitaxel-resistant CCC sublines. Finally, we determined the effects of mTORC1 inhibition on the antitumor activity of lurbinectedin-based chemotherapy. Results Lurbinectedin exhibited significant antitumor activity toward chemosensitive and chemoresistant CCC cells in vitro. An examination of mouse CCC cell xenografts revealed that lurbinectedin significantly inhibits tumor growth. Among the tested combinations, lurbinectedin plus SN-38 resulted in a significant synergistic effect. This combination also had strong synergistic effects on both the cisplatin-resistant and paclitaxel-resistant CCC cell lines. Everolimus significantly enhanced the antitumor activity of lurbinectedin-based chemotherapies. Conclusions Lurbinectedin, a new agent that targets active transcription, exhibits antitumor activity in CCC when used as a single agent and has synergistic antitumor effects when combined with irinotecan. Our results indicate that lurbinectedin is a promising agent for treating ovarian CCC, both as a first-line treatment and as a salvage treatment for recurrent lesions that develop after platinum-based or paclitaxel treatment. PMID:26986199

  19. Synthesis and evaluation of L-glutamic acid analogs as potential anticancer agents

    Directory of Open Access Journals (Sweden)

    Viswanathan C

    2008-01-01

    Full Text Available Four N-(benzenesulfonyl-L-glutamic acid bis(p-substituted phenylhydrazides were synthesized and evaluated for anticancer activity in vitro in DU-145 and PC-3 prostate cancer and in COLO-205 colon cancer cell lines by MTT assay. The analog with the nitro group substitution exhibited potent activity (% Inhibition 84.7 and 72.0 in DU-145 and PC-3 respectively at 80 mg/ml concentration. Another series of substituted 1-(benzenesulfonyl-5-oxopyrrolidine 2-carboxamides (11a-f were synthesized and evaluated for anticancer activity in vitro in colon (COLO-205, breast (Zr-75-1 and prostate (PC-3 cancer cell lines by MTT assay using adriamycin as standard. Test compounds 11a-c showed potent activity (% Inhibition 61.2 to 79.2 at 20 mg/ml and 67.2 to 87.2 at 40 mg/ml in PC-3 cell line which is superior to the activity of Adriamycin. In comparison compounds 11d-f were less potent. In Zr-75-1 cell line 11a-e showed % inhibition ranging from 32.4 to 54.9 at 10 mg/ml concentration while in COLO-205 cell line 11a-f showed poor activity.

  20. Curcumin-I Knoevenagel's condensates and their Schiff's bases as anticancer agents: synthesis, pharmacological and simulation studies.

    Science.gov (United States)

    Ali, Imran; Haque, Ashanul; Saleem, Kishwar; Hsieh, Ming Fa

    2013-07-01

    Pyrazolealdehydes (4a-d), Knoevenagel's condensates (5a-d) and Schiff's bases (6a-d) of curcumin-I were synthesized, purified and characterized. Hemolysis assays, cell line activities, DNA bindings and docking studies were carried out. These compounds were lesser hemolytic than standard drug doxorubicin. Minimum cell viability (MCF-7; wild) observed was 59% (1.0 μg/mL) whereas the DNA binding constants ranged from 1.4×10(3) to 8.1×10(5) M(-1). The docking energies varied from -7.30 to -13.4 kcal/mol. It has been observed that DNA-compound adducts were stabilized by three governing forces (Van der Wall's, H-bonding and electrostatic attractions). It has also been observed that compounds 4a-d preferred to enter minor groove while 5a-d and 6a-d interacted with major grooves of DNA. The anticancer activities of the reported compounds might be due to their interactions with DNA. These results indicated the bright future of the reported compounds as anticancer agents. PMID:23643901

  1. 3-PHENYLQUINOLINYLCHALCONE DERIVATIVES: PHARMACOPHORE MODELLING, 3D-QSAR ANALYSIS AND DOCKING STUDIES AS ANTI-CANCER AGENTS

    Directory of Open Access Journals (Sweden)

    Manoj Kumar Mahto

    2014-02-01

    Full Text Available Certain 3-Phenylquinolinylchalcone derivatives were evaluated for their anti-proliferative activities and found to exhibit anti-cancer and anti-inflammatory activities. 3D-QSAR and molecular docking approaches were performed on 3-Phenylquinolinylchalcone derivatives to understand their structural requisites and binding mode of the best fitted ligand for cancer inhibitory activity. Among them, (E-3-(3-(4-methoxyphenylquinolin-2-yl-1-phenylprop-2-en-1-one (6a was the most active compound against the growth of  H460, MCF-7, MDA-MB-231 and SKBR-3 cancer cell line respectively. Four featured hypothesis  AHRR.521 of  H460 was considered to be the best hypothesis which yielded a statistically significant 3D-QSAR model built with PLS values 3, Regression coefficient (R2 = 0.8986, Cross validation coefficient (Q2 = 0.9542, Root Mean Square Deviation (RMSD = 0.0067, Pearson-R = 1. Interestingly, the result of docking was found to correlate with the pharmacophore study where this compound was active against all six oncoproteins p53, Raf Kinase, Aurora-A-Kinase, CDK-2, Resveratrol and HSP90. The results provide detailed insights of 6a compound which can afford guidance for rational drug design of novel potent anti-cancer agents

  2. The anti-cancer agent guttiferone-A permeabilizes mitochondrial membrane: Ensuing energetic and oxidative stress implications

    International Nuclear Information System (INIS)

    Guttiferone-A (GA) is a natural occurring polyisoprenylated benzophenone with cytotoxic action in vitro and anti-tumor action in rodent models. We addressed a potential involvement of mitochondria in GA toxicity (1-25 μM) toward cancer cells by employing both hepatic carcinoma (HepG2) cells and succinate-energized mitochondria, isolated from rat liver. In HepG2 cells GA decreased viability, dissipated mitochondrial membrane potential, depleted ATP and increased reactive oxygen species (ROS) levels. In isolated rat-liver mitochondria GA promoted membrane fluidity increase, cyclosporine A/EGTA-insensitive membrane permeabilization, uncoupling (membrane potential dissipation/state 4 respiration rate increase), Ca2+ efflux, ATP depletion, NAD(P)H depletion/oxidation and ROS levels increase. All effects in cells, except mitochondrial membrane potential dissipation, as well as NADPH depletion/oxidation and permeabilization in isolated mitochondria, were partly prevented by the a NAD(P)H regenerating substrate isocitrate. The results suggest the following sequence of events: 1) GA interaction with mitochondrial membrane promoting its permeabilization; 2) mitochondrial membrane potential dissipation; 3) NAD(P)H oxidation/depletion due to inability of membrane potential-sensitive NADP+ transhydrogenase of sustaining its reduced state; 4) ROS accumulation inside mitochondria and cells; 5) additional mitochondrial membrane permeabilization due to ROS; and 6) ATP depletion. These GA actions are potentially implicated in the well-documented anti-cancer property of GA/structure related compounds. - Graphical abstract: Guttiferone-A permeabilizes mitochondrial membrane and induces cancer cell death Display Omitted Highlights: → We addressed the involvement of mitochondria in guttiferone (GA) toxicity toward cancer cells. → GA promoted membrane permeabilization, membrane potential dissipation, NAD(P)H depletion, ROS accumulation and ATP depletion. → These actions could be

  3. Anticancer properties of lamellarins.

    Science.gov (United States)

    Bailly, Christian

    2015-03-01

    In 1985 the first lamellarins were isolated from a small oceanic sea snail. Today, more than 50 lamellarins have been inventoried and numerous derivatives synthesized and tested as antiviral or anticancer agents. The lead compound in the family is lamellarin D, characterized as a potent inhibitor of both nuclear and mitochondrial topoisomerase I but also capable of directly interfering with mitochondria to trigger cancer cell death. The pharmacology and chemistry of lamellarins are discussed here and the mechanistic portrait of lamellarin D is detailed. Lamellarins frequently serve as a starting point in the design of anticancer compounds. Extensive efforts have been devoted to create novel structures as well as to improve synthetic methods, leading to lamellarins and related pyrrole-derived marine alkaloids. PMID:25706633

  4. Anticancer Properties of Lamellarins

    Directory of Open Access Journals (Sweden)

    Christian Bailly

    2015-02-01

    Full Text Available In 1985 the first lamellarins were isolated from a small oceanic sea snail. Today, more than 50 lamellarins have been inventoried and numerous derivatives synthesized and tested as antiviral or anticancer agents. The lead compound in the family is lamellarin D, characterized as a potent inhibitor of both nuclear and mitochondrial topoisomerase I but also capable of directly interfering with mitochondria to trigger cancer cell death. The pharmacology and chemistry of lamellarins are discussed here and the mechanistic portrait of lamellarin D is detailed. Lamellarins frequently serve as a starting point in the design of anticancer compounds. Extensive efforts have been devoted to create novel structures as well as to improve synthetic methods, leading to lamellarins and related pyrrole-derived marine alkaloids.

  5. Current approaches to improve the anticancer chemotherapy with alkylating agents: state of the problem in world and Ukraine.

    Directory of Open Access Journals (Sweden)

    Iatsyshyna A. P.

    2012-01-01

    Full Text Available Alkylating agents are frequently used in many established anticancer chemotherapies. They alkylate the genomic DNA at various sites. Alkylation of the guanine at the O6-position is cytotoxic, it has the strongest mutagenic potential, as well as can cause the tumor development. Alkyl groups at the O6-position of guanine are removed by the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT. The effectiveness of alkylating chemotherapy is limited by MGMT in cancer cells and adverse toxic side effects in normal cells. Different approaches consisting in the modulation of the MGMT expression and activity are under development now to improve the cancer chemotherapy. They include two main directions, in particular, the increase in chemosensitivity of cancer cells to alkylating drugs and the protection of normal cells from the toxic side effects of chemotherapy. This review is focused on current attempts to improve the alkylating chemotherapy of malignant tumours worldwide and state of the issue in Ukraine

  6. New testosterone derivatives as semi-synthetic anticancer agents against prostate cancer: synthesis and preliminary biological evaluation.

    Science.gov (United States)

    Morin, Nathalie; Bruneau, Julie; Fortin, Sebastien; Brasseur, Kevin; Leblanc, Valerie; Asselin, Eric; Berube, Gervais

    2015-01-01

    Prostate cancer (PC) is a major health issue in the world. Treatments of localized PC are quite efficient and usually involve surgery, radiotherapy and/or hormonal therapy. Metastatic PC is however rarely curable to this day. Treatments of metastatic PC involve radiotherapy, chemotherapy and hormonal treatment such as orchiectomy, antiandrogens and luteinizing hormone-releasing hormone agonists. The suppression of tumor growth by hormonal treatment is efficient but overtime resistance still occurs and the disease progresses. Thus, more urgently than ever there is a need for discovery of new treatment options for castration-resistant PC (CRPC). Hence, we designed and tested a series of amide derivatives located at position 7α of testosterone as prospective "natural" or "semisynthetic" anticancer agents against CRPC with the goal of discovering therapeutic alternatives for the disease. This manuscript describes an efficient path towards the target molecules that are made in only 6 or 7 chemical steps from testosterone in good overall yields. This strategy can be used to make several compounds of interest that present higher biological activity than the classic antiandrogen; cyproterone acetate (3). The best testosterone-7α-amide was the N-2-pyridylethylamide (25) which was as active as the antiandrogen cyproterone acetate (3) on androgen-dependent LNCaP cells and 2.7 times more active on androgen-independent PC3 prostate cancer cells. The results obtained show the synthetic feasibility and the potential for future development of this unique class of semi-synthetic anticancer agents that offer the premise of new treatment modalities for patients afflicted with CRPC. PMID:25675439

  7. Preclinical Assessment of Vernonia amygdalina Leaf Extracts as DNA Damaging Anti-cancer Agent in the Management of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ernest Izevbigie

    2008-12-01

    Full Text Available Breast cancer is the leading cause of death among women between 40 and 55 years of age and is the second overall cause of death among women. Fortunately, the mortality rate from breast cancer has decreased in recent years due to an increased emphasis on early detection and more effective treatments. Despite early detection, conventional and chemotherapeutic methods of treatment, about 7% of women still died every year. Hence, the aim of the present study was to assess the therapeutic efficacy of Vernonia amygdalina (VA leaf extracts as anti-cancer agent against human breast cancer in vitro using the MTT [3-(4, 5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide] and alkaline single cell gel electrophoresis (Comet assays, respectively. In this experiment, human breast adenocarcinoma (MCF-7 cells were treated with different doses of VA leaf extracts for 48 hours. Data obtained from the MTT assay showed that VA significantly ((P < 0.05 reduced the viability of MCF-7 cells in a dose-dependent manner upon 48 hours of exposure. Data generated from the comet assay also indicated a slight dose-dependent increase in DNA damage in MCF-7 cells associated with VA treatment. We observed a slight increase in comet tail-length, tail arm and tail moment, as well as in percentages of DNA cleavage at all doses tested, showing an evidence that VA-induced minimal genotoxic damage in MCF-7 cells. Taken together, our findings suggest that VA treatment moderately (P < 0.05 reduces cellular viability and induces minimal DNA damage in MCF-7 cells. These findings provide evidence that VA extracts represent a DNA-damaging anti-cancer agent against breast cancer and its mechanisms of action functions, at least in part, through minimal DNA damage and moderate toxicity in tumors cells.

  8. Hypersensitivity reactions to anticancer agents: Data mining of the public version of the FDA adverse event reporting system, AERS

    Directory of Open Access Journals (Sweden)

    Sakaeda Toshiyuki

    2011-10-01

    Full Text Available Abstract Background Previously, adverse event reports (AERs submitted to the US Food and Drug Administration (FDA database were reviewed to confirm platinum agent-associated hypersensitivity reactions. The present study was performed to confirm whether the database could suggest the hypersensitivity reactions caused by anticancer agents, paclitaxel, docetaxel, procarbazine, asparaginase, teniposide, and etoposide. Methods After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving candidate agents were analyzed. The National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 was applied to evaluate the susceptibility to hypersensitivity reactions, and standardized official pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Results Based on 1,644,220 AERs from 2004 to 2009, the signals were detected for paclitaxel-associated mild, severe, and lethal hypersensitivity reactions, and docetaxel-associated lethal reactions. However, the total number of adverse events occurring with procarbazine, asparaginase, teniposide, or etoposide was not large enough to detect signals. Conclusions The FDA's adverse event reporting system, AERS, and the data mining methods used herein are useful for confirming drug-associated adverse events, but the number of co-occurrences is an important factor in signal detection.

  9. Design and synthesis of diamide-coupled benzophenones as potential anticancer agents.

    Science.gov (United States)

    Zabiulla; Shamanth Neralagundi, H G; Bushra Begum, A; Prabhakar, B T; Khanum, Shaukath Ara

    2016-06-10

    A series of diamide-coupled benzophenone, 2-(4-benzoyl-phenoxy)-N-{2-[2-(4-benzoyl-phenoxy)-acetylamino]-phenyl}-acetamide analogues (9a-l) were synthesized by multistep reactions and all compounds were well characterized. Among the series (9a-l), compound 9k with three methyl groups at ortho position in rings A, B, and D and bromo group at the para position in ring E was selected as a lead compound by screening through multiple cancer cell types by in-vitro cytotoxic and antiproliferative assay systems. Also, the cytotoxic nature of the compound 9k resulted the regression of the tumor growth in-vivo, which could be due to decreased vascularisation in the peritoneum lining of the mice which regress the tumor growth. The results were reconfirmed in-vivo chorioallantoic membrane model which indicates a scope of developing 9k into potent anticancer drug in near future. PMID:27027818

  10. RasGRPs are targets of the anti-cancer agent ingenol-3-angelate.

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    Xiaohua Song

    Full Text Available Ingenol-3-angelate (I3A is a non-tumor promoting phorbol ester-like compound identified in the sap of Euphoria peplus. Similar to tumor promoting phorbol esters, I3A is a diacylglycerol (DAG analogue that binds with high affinity to the C1 domains of PKCs, recruits PKCs to cellular membranes and promotes enzyme activation. Numerous anti-cancer activities have been attributed to I3A and ascribed to I3A's effects on PKCs. We show here that I3A also binds to and activates members of the RasGRP family of Ras activators leading to robust elevation of Ras-GTP and engagement of the Raf-Mek-Erk kinase cascade. In response to I3A, recombinant proteins consisting of GFP fused separately to full-length RasGRP1 and RasGRP3 were rapidly recruited to cell membranes, consistent with direct binding of the compound to RasGRP's C1 domain. In the case of RasGRP3, IA3 treatment led to positive regulatory phosphorylation on T133 and activation of the candidate regulatory kinase PKCδ. I3A treatment of select B non-Hodgkin's lymphoma cell lines resulted in quantitative and qualitative changes in Bcl-2 family member proteins and induction of apoptosis, as previously demonstrated with the DAG analogue bryostatin 1 and its synthetic analogue pico. Our results offer further insights into the anticancer properties of I3A, support the idea that RasGRPs represent potential cancer therapeutic targets along with PKC, and expand the known range of ligands for RasGRP regulation.

  11. Electrochemical and calorimetric investigation of interaction of novel biscationic anticancer agents with DNA; Investigacao eletroquimica e calorimetrica da interacao de novos agentes antitumorais biscationicos com DNA

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Lauris Lucia da; Donnici, Claudio Luis; Lopes, Julio Cesar Dias, E-mail: cdonnici@terra.com.br [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Inst. de Ciencias Exatas. Dept. de Quimica; Goulart, Marilia Oliveira Fonseca; Abreu, Fabiane Caxico de; Paula, Francine Santos de [Universidade Federal de Alagoas (UFAL), Maceio, AL (Brazil). Campus A.C. Simoes. Inst. de Quimica e Biotecnologia; Bravo, Carlos E. Salas; Santoro, Marcelo Matos [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Dept. de Bioquimica e Imunologia; Denadai, Angelo Marcio Leite [Centro Federal de Educacao Tecnologica, Timoteo, MG (Brazil). Campus VII; Santos, Alexandre Martins Costa [Universidade Federal do Espirito Santo, Vitoria, ES (Brazil). Dept. de Ciencias Fisiologicas; Montanari, Carlos Alberto [Universidade de Sao Paulo, Sao Carlos, SP (Brazil). Inst. de Quimica

    2012-07-01

    Biscationic amidines bind in the DNA minor groove and present biological activity against a range of infectious diseases. Two new biscationic compounds (bis-{alpha}-{omega}-S-thioureido, amino and sulfide analogues) were synthesized in good yields and fully characterized, and their interaction with DNA was also investigated. Isothermal titration calorimetry (ITC) was used to measure the thermodynamic properties of binding interactions between DNA and these ligands. A double stranded calf thymus DNA immobilized on an electrode surface was used to study the possible DNA-interacting abilities of these compounds towards dsDNA in situ. A remarkable interaction of these compounds with DNA was demonstrated and their potential application as anticancer agents was furthered. (author)

  12. Zampanolide and Dactylolide: Cytotoxic Tubulin-Assembly Agents and Promising Anticancer Leads

    OpenAIRE

    Chen, Qiao-Hong; Kingston, David G. I.

    2014-01-01

    Zampanolide is a marine natural macrolide and a recent addition to the family of microtubule-stabilizing cytotoxic agents. Zampanolide exhibits unique effects on tubulin assembly and is more potent than paclitaxel against several multi-drug resistant cancer cell lines. A high-resolution crystal structure of xB-tubulin in complex with zampanolide explains how taxane-site microtubule-stabilizing agents promote microtubule assemble and stability. This review provides an overview of current devel...

  13. Zampanolide and dactylolide: cytotoxic tubulin-assembly agents and promising anticancer leads

    OpenAIRE

    Chen, Qiao-Hong; Kingston, David G. I.

    2014-01-01

    Covering: through January 2014 Zampanolide is a marine natural macrolide and a recent addition to the family of microtubule-stabilizing cytotoxic agents. Zampanolide exhibits unique effects on tubulin assembly and is more potent than paclitaxel against several multi-drug resistant cancer cell lines. A high-resolution crystal structure of αβ-tubulin in complex with zampanolide explains how taxane-site microtubule-stabilizing agents promote microtubule assemble and stability. This review provid...

  14. Proof of concept for inhibiting metastasis: circulating tumor cell-triggered localized release of anticancer agent via a structure-switching aptamer.

    Science.gov (United States)

    Chen, Nandi; Yang, Xiaohai; Wang, Qing; Jian, Lixin; Shi, Hui; Qin, Shiya; Wang, Kemin; Huang, Jin; Liu, Wenjing

    2016-05-21

    Existing drug delivery systems were not suitable for killing cells in the circulatory system specifically. Herein, we developed a novel localized drug delivery strategy, in which the release of anticancer agents was specifically triggered by circulating tumor cells. Meanwhile, damage to non-target cells was avoided. PMID:27121864

  15. Progress Toward the Development of Noscapine and Derivatives as Anticancer Agents.

    Science.gov (United States)

    DeBono, Aaron; Capuano, Ben; Scammells, Peter J

    2015-08-13

    Many nitrogen-moiety containing alkaloids derived from plant origins are bioactive and play a significant role in human health and emerging medicine. Noscapine, a phthalideisoquinoline alkaloid derived from Papaver somniferum, has been used as a cough suppressant since the mid 1950s, illustrating a good safety profile. Noscapine has since been discovered to arrest cells at mitosis, albeit with moderately weak activity. Immunofluorescence staining of microtubules after 24 h of noscapine exposure at 20 μM elucidated chromosomal abnormalities and the inability of chromosomes to complete congression to the equatorial plane for proper mitotic separation ( Proc. Natl. Acad. Sci. U. S. A. 1998 , 95 , 1601 - 1606 ). A number of noscapine analogues possessing various modifications have been described within the literature and have shown significantly improved antiprolific profiles for a large variety of cancer cell lines. Several semisynthetic antimitotic alkaloids are emerging as possible candidates as novel anticancer therapies. This perspective discusses the advancing understanding of noscapine and related analogues in the fight against malignant disease. PMID:25811651

  16. The Use of 1α,25-Dihydroxyvitamin D3 as an Anticancer Agent

    Directory of Open Access Journals (Sweden)

    Ewa Marcinkowska

    2016-05-01

    Full Text Available The notion that vitamin D can influence the incidence of cancer arose from epidemiological studies. The major source of vitamin D in the organism is skin production upon exposure to ultra violet-B. The very first observation of an inverse correlation between exposure of individuals to the sun and the likelihood of cancer was reported as early as 1941. In 1980, Garland and Garland hypothesised, from findings from epidemiological studies of patients in the US with colon cancer, that vitamin D produced in response to sun exposure is protective against cancer as opposed to sunlight per se. Later studies revealed inverse correlations between sun exposure and the occurrence of prostate and breast cancers. These observations prompted laboratory investigation of whether or not vitamin D had an effect on cancer cells. Vitamin D is not active against cancer cells, but the most active metabolite 1α,25-dihydroxyvitamin D3 (1,25D has profound biological effects. Here, we review the anticancer action of 1,25D, clinical trials of 1,25D to date and the prospects of the future therapeutic use of new and low calcaemic analogues.

  17. Synthesis and evaluation of polymeric gold glyco-conjugates as anti-cancer agents.

    Science.gov (United States)

    Ahmed, Marya; Mamba, Saul; Yang, Xiao-Hong; Darkwa, James; Kumar, Piyush; Narain, Ravin

    2013-06-19

    The antitumor activity of organo-gold compounds is a focus of research from the past two decades. A variety of gold stabilizing ligands such as vitamins and xanthanes have been prepared and explored for their 'chelating effect' as well as for their antitumor activity. Dithiocarbamates (DTC) compounds and their metallic conjugates have been well explored for their antiproliferative activities. In this study, glycopolymer based DTC-conjugates are prepared by reversible addition-fragmentation chain transfer polymerization (RAFT) and subsequently modified with gold(I) phosphine. These polymer-DTC derivatives and their gold compounds are tested for their in vitro toxicity in both normal and cancer cell lines. The Au(I) phosphine conjugated cationic glycopolymers of 10 kDa and 30 kDa are evaluated for their cytotoxicity profiles using MTT assay. Au(I) compounds are well-known for their mitochondrial toxicity, hence hypoxic cell lines bearing unusually enlarged mitochondria are subjected to these anticancer compounds. It is concluded that these polymeric DTC derivatives and their gold conjugates indeed show higher accumulation as well as cytotoxicity to cancer cells under hypoxic conditions in comparison to the normoxic ones. Hypoxic MCF-7 cells showed significant sensitivity toward the low molecular weight (10 kDa) glycopolymer-Au(I) complexes. PMID:23631753

  18. Discovery and optimization of novel dual dithiocarbamates as potent anticancer agents.

    Science.gov (United States)

    Li, Ri-Dong; Wang, Hui-Ling; Li, Ying-Bo; Wang, Zhong-Qing; Wang, Xin; Wang, Yi-Tao; Ge, Ze-Mei; Li, Run-Tao

    2015-03-26

    A series of dual dithiocarbamates were synthesized and evaluated for their in-vitro anticancer activities on human non-small cell lung cancer cell line H460. Nine compounds exhibited significant antiproliferative activities with IC50 less than 1 μM. Among them, compound 14m showed the highest inhibitory activity against H460 cell and inhibited the growth of nine types of tumor cells with IC50 values less than 1 μM. It also achieved IC50 of 54 nM and 23 nM against HepG2 and MCF-7 cell lines, respectively. Preliminary structure-activity relationship study indicated that: a) when the methyl group (region A) is substituted with benzene rings, ortho substitution on the benzene ring is favored for activity; b) substitution with heterocyclic structures at region A exhibited greater impact on the anti-tumor activity of compounds, in which pyridine ring, thiazole ring, coumarin and benzo[b]thiophene are favored and quinoline ring is the most favored; c) substitution with different amines (region B) also showed marked effect on the activity of compounds and dimethylamine and morpholine are preferred to other tested amines. PMID:25725374

  19. The Use of 1α,25-Dihydroxyvitamin D3 as an Anticancer Agent

    Science.gov (United States)

    Marcinkowska, Ewa; Wallace, Graham R.; Brown, Geoffrey

    2016-01-01

    The notion that vitamin D can influence the incidence of cancer arose from epidemiological studies. The major source of vitamin D in the organism is skin production upon exposure to ultra violet-B. The very first observation of an inverse correlation between exposure of individuals to the sun and the likelihood of cancer was reported as early as 1941. In 1980, Garland and Garland hypothesised, from findings from epidemiological studies of patients in the US with colon cancer, that vitamin D produced in response to sun exposure is protective against cancer as opposed to sunlight per se. Later studies revealed inverse correlations between sun exposure and the occurrence of prostate and breast cancers. These observations prompted laboratory investigation of whether or not vitamin D had an effect on cancer cells. Vitamin D is not active against cancer cells, but the most active metabolite 1α,25-dihydroxyvitamin D3 (1,25D) has profound biological effects. Here, we review the anticancer action of 1,25D, clinical trials of 1,25D to date and the prospects of the future therapeutic use of new and low calcaemic analogues. PMID:27187375

  20. The Use of 1α,25-Dihydroxyvitamin D₃ as an Anticancer Agent.

    Science.gov (United States)

    Marcinkowska, Ewa; Wallace, Graham R; Brown, Geoffrey

    2016-01-01

    The notion that vitamin D can influence the incidence of cancer arose from epidemiological studies. The major source of vitamin D in the organism is skin production upon exposure to ultra violet-B. The very first observation of an inverse correlation between exposure of individuals to the sun and the likelihood of cancer was reported as early as 1941. In 1980, Garland and Garland hypothesised, from findings from epidemiological studies of patients in the US with colon cancer, that vitamin D produced in response to sun exposure is protective against cancer as opposed to sunlight per se. Later studies revealed inverse correlations between sun exposure and the occurrence of prostate and breast cancers. These observations prompted laboratory investigation of whether or not vitamin D had an effect on cancer cells. Vitamin D is not active against cancer cells, but the most active metabolite 1α,25-dihydroxyvitamin D₃ (1,25D) has profound biological effects. Here, we review the anticancer action of 1,25D, clinical trials of 1,25D to date and the prospects of the future therapeutic use of new and low calcaemic analogues. PMID:27187375

  1. Design, synthesis and biological evaluation of novel pyridine derivatives as anticancer agents and phosphodiesterase 3 inhibitors

    Science.gov (United States)

    Abadi, Ashraf H.; Ibrahim, Tamer M.; Abouzid, Khaled M.; Lehmann, Jochen; Tinsley, Heather N.; Gary, Bernard D.; Piazza, Gary A.

    2016-01-01

    Two series of 4,6-diaryl-2-imino-1,2-dihydropyridine-3-carbonitriles and their isosteric 4,6-diaryl-2- oxo-1,2-dihydropyridine-3-carbonitriles were synthesized through a combinatorial approach. The prepared analogues were evaluated for their in vitro capacity to inhibit PDE3A and the growth of the human HT-29 colon adenocarcinoma tumor cell line. Compound 6-(4-bromophenyl)-4-(2-ethoxyphenyl)-2- imino-1,2-dihydropyridine-3-carbonitrile (Id) exhibited the strongest PDE3 inhibition when cGMP but not cAMP is the substrate with a IC50of 27 μM, which indicates a highly selective mechanism of enzyme inhibition. On the other hand, compound 6-(1,3-benzodioxol-5-yl)-4-(2-ethoxyphenyl)-2-imino-1,2- dihydropyridine-3-carbonitrile (Ii) was the most active in inhibiting colon tumor cell growth with a IC50 of 3 μM. The electronic effects, steric effects and conformational aspects of Id seem to be the most crucial for the PDE3 inhibition. Meanwhile, steric factors and the H-bonding capability seem to be the most important factors for tumor cell growth inhibitory activity. Conversely, there is no direct correlation between PDE3 inhibition and anticancer activity for the prepared compounds. An in silico docking experiment indicates the potential involvement of other potential molecular targets such as PIM-1 kinase to explain its tumor cell growth inhibitory activity. PMID:19628397

  2. Synthesis, cytotoxic activity evaluation and HQSAR study of novel isosteviol derivatives as potential anticancer agents.

    Science.gov (United States)

    Liu, Cong-Jun; Yu, Shu-Ling; Liu, Yan-Ping; Dai, Xing-Jie; Wu, Ya; Li, Rui-Jun; Tao, Jing-Chao

    2016-06-10

    A series of novel isosteviol derivatives bearing amino alcohol and thiourea fragments have been stereo-selectively synthesized and screened for their in vitro cytotoxic activities against three human cancer cell lines (HCT-116, HGC-27 and JEKO-1). The results demonstrated that these compounds exhibited prominent cytotoxicities. Especially, the compound Iw displayed the most potent anticancer activities against HCT-116 cell with IC50 value of 1.450 μM. On the basis of this bioassay results, these derivatives were further investigated by the hologram quantitative structure-activity relationship (HQSAR) technique. The optimal HQSAR model with q(2) = 0.663, r(2) = 0.895, SEE = 0.179 was generated using A/B/H/Ch as fragment distinction parameters and 4-7 as fragment size. This model was employed to predict the cytotoxic activities of test set compounds, and the predicted values were in good agreement with the experimental results. The contribution maps derived from the optimal model explained the individual atomic contribution to the total activity of single molecule. PMID:26994841

  3. In Vitro Antibacterial, Antifungal, Antibiofilm, Antioxidant, and Anticancer Properties of Isosteviol Isolated from Endangered Medicinal Plant Pittosporum tetraspermum

    Directory of Open Access Journals (Sweden)

    Naif Abdullah Al-Dhabi

    2015-01-01

    Full Text Available This study aimed to investigate the in vitro antibacterial, antifungal, antibiofilm, antioxidant, and anticancer properties of isosteviol isolated from endangered medicinal plant Pittosporum tetraspermum. Pure compound was obtained and characterized by column chromatography followed by 1H NMR, 13C NMR, IR, and mass spectral analysis. The antimicrobial activities of the compound were assessed by the broth microdilution method and the antioxidant properties were determined using reducing ability assay, DPPH scavenging assay, hydroxyl radical scavenging activity, and superoxide radical scavenging assay. Anticancer study was evaluated by following MTT assay. Column purification and spectrocopical analysis lead to identifying isosteviol from the crude ethyl acetate extract. The compound exhibited significant activity against bacteria such as Staphylococcus epidermidis (125 µg/mL, Staphylococcus aureus (125 µg/mL, and Klebsiella pneumoniae (62.5 µg/mL. The MIC of the compound against Candida albicans, Aspergillus niger, and Trichophyton mentagrophytes was 62.5, 125, and 500 µg/mL, respectively. The compound showed comparatively better antibiofilm activity against E. coli, S. typhi, and P. aeruginosa. Furthermore, it exhibited good antioxidant properties. Anticancer properties of the compound against Vero and MCF7 cell lines were its advantage. Novel isosteviol would be useful to reduce the infectious diseases caused by pathogenic microorganisms or slow the progress of various oxidative stress-related diseases.

  4. Preparation, characterization and in vitro evaluation of sterically stabilized liposome containing a naphthalenediimide derivative as anticancer agent.

    Science.gov (United States)

    Parise, Amelia; Milelli, Andrea; Tumiatti, Vincenzo; Minarini, Anna; Neviani, Paolo; Zuccari, Guendalina

    2015-01-01

    The aim of this study was to incorporate a new naphthalenediimide derivative (AN169) with a promising anticancer activity into pegylated liposomes to an extent that allows its in vitro and in vivo testing without use of toxic solvent. AN169-loaded liposomes were prepared using the thin-film hydration method and characterized for size, polydispersity index, drug content and drug release. We examined their lyophilization ability in the presence of cryoprotectants (trehalose, sucrose and lysine) and the long-term stability of the lyophilized products stored at 4 °C for 3 and 6 months by particle size changes and drug leakage. AN169 was successfully loaded into liposomes with an entrapment efficiency of 87.3 ± 2.5%. The hydrodynamic diameter of these liposomes after sonication was ∼ 145 nm with a high degree of monodispersity. Trehalose was found to be superior to the other lyoprotectants. In particular, trehalose 1:10 lipid:cryoprotectant molar ratio may provide stable lyophilized liposomes with the conservation of physicochemical properties upon freeze-drying and long-term storage conditions. We also assessed their in vitro antitumor activity in human cancer cell lines (HTLA-230 neuroblastoma, Mel 3.0 melanoma, OVCAR-3 ovarian carcinoma and SV620 prostate cancer cells). However, only after 72 h incubation, loaded liposomes showed almost the same IC50 as free AN169. In conclusion, we developed a stable lyophilized liposomal formulation for intravenous administration of AN169 as anticancer drug, with the advantage of avoiding the use of potentially toxic solubilizing agents for future in vivo experiments. PMID:24286206

  5. In vitro and in vivo evaluation of organometallic gold(I) derivatives as anticancer agents.

    Science.gov (United States)

    García-Moreno, Elena; Tomás, Alejandro; Atrián-Blasco, Elena; Gascón, Sonia; Romanos, Eduardo; Rodriguez-Yoldi, Mary Jesus; Cerrada, Elena; Laguna, Mariano

    2016-02-14

    Alkyne gold(I) derivatives with the water soluble phosphanes PTA (1,3,5-triaza-7-phosphaadamantane) and DAPTA (3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane) were described and their anticancer potential against the colon cancer cell line Caco-2 (PD7 and TC7 clones) was studied. Strong antiproliferative effects are found, for all the new complexes, to be even more pronounced than for the reference drug cisplatin, and similar to auranofin. The interaction of these derivatives with bovine serum albumin (BSA) was studied by fluorescence spectroscopy. The types of quenching and binding constants were determined by a fluorescence quenching method. Moderate values of the binding constants are calculated for the tested derivatives indicating that these complexes can be stored and carried easily by this protein in the body. The study of the thermodynamic parameters in the case of [Au(C[triple bond, length as m-dash]CCH2Spyridine)(PTA)] points out to the presence of van der Waals interactions or hydrogen bonding between the metallic complex and the protein. In addition, the complex [Au(C[triple bond, length as m-dash]CCH2Spyridine)(PTA)] has shown inhibition in colon cancer proliferation of HTC-116-luc2 cell lines via the apoptotic pathway and S-phase arrest of the cell cycle. Intraperitoneal injection of this derivative in athymic nude mice inoculated with HTC-116-luc2 cells prolonged their survival and displayed moderate inhibition of the tumour growth with no subsequent organ (kidney and liver) damage after treatment. PMID:26469679

  6. Mitochondrial complex II, a novel target for anti-cancer agents

    Czech Academy of Sciences Publication Activity Database

    Klučková, Katarína; Bezawork-Geleta, A.; Rohlena, Jakub; Dong, L.; Neužil, Jiří

    2013-01-01

    Roč. 1827, č. 5 (2013), s. 552-564. ISSN 0005-2728 R&D Projects: GA ČR(CZ) GAP301/10/1937; GA ČR GAP301/12/1851 Institutional research plan: CEZ:AV0Z50520701 Keywords : Mitochondrion * Complex II * Anti- cancer agent Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.829, year: 2013

  7. The Quest for a Simple Bioactive Analog of Paclitaxel as a Potential Anticancer Agent

    OpenAIRE

    Kingston, David G I; Snyder, James P.

    2014-01-01

    Conspectus Paclitaxel (PTX), introduced into the clinic in 1991, has revealed itself as an effective antimicrotubule drug for treatment of a range of otherwise intractable cancers. Along with docetaxel (DTX) and in combination with other agents such as cisplatin, it has proven to be a first-line therapy. Unfortunately, PTX and DTX carry severe liabilities such as debilitating side effects, rapid onset of resistance, and rather complex molecular structures offering substantial challenges to ea...

  8. Synthesis and evaluation of nitrate derivatives of colchicine as anticancer agents

    Institute of Scientific and Technical Information of China (English)

    Li Hong Shen; Ya Li; Da Hai Zhang; Yi Sheng Lai; Li Jie Liu

    2011-01-01

    To search for more potent antitumor agent, a series of novel nitric oxide-donating colchicine (Col) derivatives (6a-f, 8a and b) were synthesized by coupling nitrates with N-methyl colchiceinamide. Their cytotoxicity against four human cancer cell lines in vitro were evaluated by MTT assay. It was found that many of the derivatives displayed significant activity, particularly, compounds 6c, 8a and 8b showed more potent cytotoxic activities than Col.

  9. Study of combination treatment effect of the {sup 166}Ho and anticancer agents in-vitro

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, S. M.; Choi, S. J.; Park, K. B. [KAERI, Taejon (Korea, Republic of)

    2003-10-01

    For the development of new controlled drug delivery systems, the application of combination therapy using radioisotopes and tumor static agents has drawn great attention. This study was designed to estimate the treatment effect of the combination therapy with Holmium ({sup 166}Ho) and tumor static agents. Ho-166 was produced at the KAERI using HANARO reactor. The drugs applied were Sunpla, Methotrexate and Doxorubicin. Human glioblastoma (T98G), adenocarcinoma (MKN45), hepatocellular (Hep3B), lung carcinoma (Calu6), ovary adenocarcinoma (NIH:OVCAR- 3) and rat glioma (C6) were used. The cell cytotoxicity on the tumor cell lines determined by MTT assay. In the case where the chemotherapeutic agent was solely applied to the cell lines, the IC{sub 50} values wer e 2.4x10{sup -5}M of the Sunpla for MKN45 and 4.23x10{sup -6}M of the Doxorubicin for Calu6. The radioactivity of Ho-166 occurring 20% apoptosis was 10{mu}Ci. As for Sunpla and Doxorubicin, the value of IC20 was dependent on the cell lines used. The combination treatment of {sup 166}Ho and drug was to improve therapeutic success rate in T98G, MKN45, Hep3B, and Calu6. From this in vitro study it can be concluded that combining 166Ho radionuclide therapy and chemotherapy could enhance the effect of each in eliminating proliferating tumor cells.

  10. Aloe vera Gel: Effective Therapeutic Agent against Multidrug-Resistant Pseudomonas aeruginosa Isolates Recovered from Burn Wound Infections

    Directory of Open Access Journals (Sweden)

    Mehdi Goudarzi

    2015-01-01

    Full Text Available Objective. Aloe vera is an herbal medicinal plant with biological activities, such as antimicrobial, anticancer, anti-inflammatory, and antidiabetic ones, and immunomodulatory properties. The purpose of this study was investigation of in vitro antimicrobial activity of A. vera gel against multidrug-resistant (MDR Pseudomonas aeruginosa isolated from patients with burn wound infections. Methods. During a 6-month study, 140 clinical isolates of P. aeruginosa were collected from patients admitted to the burn wards of a hospital in Tehran, Iran. Antimicrobial susceptibility test was carried out against the pathogens using the A. vera gel and antibiotics (imipenem, gentamicin, and ciprofloxacin. Results. The antibiogram revealed that 47 (33.6% of all isolates were MDR P. aeruginosa. The extract isolated from A. vera has antibacterial activity against all of isolates. Also, 42 (89.4% isolates were inhibited by A. vera gel extract at minimum inhibitory concentration (MIC ≤ 200 µg/mL. MIC value of A. vera gel for other isolates (10.6% was 800 µg/mL. All of MDR P. aeruginosa strains were inhibited by A. vera at similar MIC50 and MIC90 200 µg/mL. Conclusion. Based on our results, A. vera gel at various concentrations can be used as an effective antibacterial agent in order to prevent wound infection caused by P. aeruginosa.

  11. Synthesis and evaluation of single-wall carbon nanotube-paclitaxel-folic acid conjugate as an anti-cancer targeting agent.

    Science.gov (United States)

    Tavakolifard, Sara; Biazar, Esmaeil; Pourshamsian, Khalil; Moslemin, Mohammad H

    2016-08-01

    Single-wall carbon nanotubes (SWCNT) represent a novel nanomaterial applied in various nanotechnology fields because of their surface chemistry properties and high drug cargo capacity. In this study, SWCNT are pre-functionalized covalently with paclitaxel (PTX) - an anticancer drug, and folic acid (FA), as a targeting agent for many tumors. The samples are investigated and evaluated by different analyses such as Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), absorption spectroscopic measurements (UV-Visible), elemental analysis, and cell analyses with cancer cell line cultures. The results show good conjugation of the targeting molecule and the anticancer drug on the surface of the carbon nanotubes (CNT). This work demonstrates that the SWCNT-PTX-FA system is a potentially useful system for the targeted delivery of anticancer drugs. PMID:25783856

  12. The Optimum Irradiation Dose in Preservation of Mahkota Dewa (Phaleria macrocarpa (Scheff) Boerl.) As Anticancer Agent

    International Nuclear Information System (INIS)

    The purpose of this experiment was to obtain the optimum irradiation dose, in order to preserve and protect the damage of anticancer compounds in mahkota dewa bark. The specimens of mahkota dewa bark were irradiated using 60Co at the variation doses of 0; 5; 7,5 ; 10; 15; and 20 kGy, respectively at the dose rate of 10 kGy/h. The irradiated and control samples were macerated in n-hexane and ethyl acetate, respectively, then the ethyl acetate extract was then fractionated using chromatography column to obtain 8 fractions. The examination of irradiated and control samples of mahkota dewa bark against microbe contaminants showed that irradiation at doses ≥5 kGy could inhibit the growth of bacteria, mold and yeast and destroyed them. The cytotoxicity test of irradiated ethyl acetate extract of mahkota dewa bark against leukemia L1210 cell showed that irradiation at the dose up to 20 kGy can decreased cytotoxic activities performance, however these IC50 values lower than 50 μg/ml, which is the cytotoxic activity threshold for extract. The cytotoxic activity test of fraction 6, the most active fraction in mahkota dewa bark, showed that irradiation at the dose up to 20 kGy can also decreased the cytotoxic activities performance, however these IC50 values was lower than 20 μg/ml, which is the cytotoxic activity threshold for fraction. Analysis of 2,4’-dihydroxy-4 methoxy benzophenone-2-O-β-D-glucopyranoside by high performance liquid chromatography (HPLC) in fraction 6 of irradiated samples showed that the concentration of this compound in irradiated samples significantly decreased, compared to the control sample. Decreasing the concentration of 2,4’-dihydroxy-4 methoxy benzophenone-2-O-β-D-glucopyranoside was not comparable to the cytotoxic activity of ethyl acetate extract or fraction 6, therefore this compound can not be used as marker of irradiation effect on decreasing the cytotoxic activity of the mahkota dewa bark. Irradiation at doses of 5 up to 20 kGy is

  13. Use of Yeast Chemigenomics and COXEN Informatics in Preclinical Evaluation of Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Steven C. Smith

    2011-01-01

    Full Text Available Bladder cancer metastasis is virtually incurable with current platinum-based chemotherapy. We used the novel COXEN informatic approach for in silico drug discovery and identified NSC-637993 and NSC-645809 (C1311, both imidazoacridinones, as agents with high-predicted activity in human bladder cancer. Because even highly effective monotherapy is unlikely to cure most patients with metastasis and NSC-645809 is undergoing clinical trials in other tumor types, we sought to develop the basis for use of C1311 in rational combination with other agents in bladder cancer. Here, we demonstrate in 40 human bladder cancer cells that the in vitro cytotoxicity profile for C1311 correlates with that of NSC-637993 and compares favorably to that of standard of care chemotherapeutics. Using genomewide patterns of synthetic lethality of C1311 with open reading frame knockouts in budding yeast, we determined that combining C1311 with a taxane could provide mechanistically rational combinations. To determine the preclinical relevance of these yeast findings, we evaluated C1311 singly and in doublet combination with paclitaxel in human bladder cancer in the in vivo hollow fiber assay and observed efficacy. By applying COXEN to gene expression data from 40 bladder cancer cell lines and 30 human tumors with associated clinical response data to platinum-based chemotherapy, we provide evidence that signatures of C1311 sensitivity exist within nonresponders to this regimen. Coupling COXEN and yeast chemigenomics provides rational combinations with C1311 and tumor genomic signatures that can be used to select bladder cancer patients for clinical trials with this agent.

  14. Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents

    Directory of Open Access Journals (Sweden)

    Petrillo Richard L

    2010-02-01

    Full Text Available Abstract Histone deacetylases (HDACs can regulate expression of tumor suppressor genes and activities of transcriptional factors involved in both cancer initiation and progression through alteration of either DNA or the structural components of chromatin. Recently, the role of gene repression through modulation such as acetylation in cancer patients has been clinically validated with several inhibitors of HDACs. One of the HDAC inhibitors, vorinostat, has been approved by FDA for treating cutaneous T-cell lymphoma (CTCL for patients with progressive, persistent, or recurrent disease on or following two systemic therapies. Other inhibitors, for example, FK228, PXD101, PCI-24781, ITF2357, MGCD0103, MS-275, valproic acid and LBH589 have also demonstrated therapeutic potential as monotherapy or combination with other anti-tumor drugs in CTCL and other malignancies. At least 80 clinical trials are underway, testing more than eleven different HDAC inhibitory agents including both hematological and solid malignancies. This review focuses on recent development in clinical trials testing HDAC inhibitors as anti-tumor agents.

  15. Challenges in preclinical to clinical translation for anticancer carrier-mediated agents.

    Science.gov (United States)

    Lucas, Andrew T; Madden, Andrew J; Zamboni, William C

    2016-09-01

    Major advances in carrier-mediated agents (CMAs), which include nanoparticles and conjugates, have revolutionized drug delivery capabilities over the past decade. While providing numerous advantages over their small-molecule counterparts, there is substantial variability in how individual CMA formulations and patient characteristics affect the pharmacology, pharmacokinetics (PK), and pharmacodynamics (PD) (efficacy and toxicity) of these agents. Development or selection of animal models is used to predict the effects within a particular human disease. A breadth of studies have begun to emphasize the importance of preclinical animal models in understanding and evaluating the interaction between CMAs and the immune system and tumor matrix, which ultimately influences CMA PK (clearance and distribution) and PD (efficacy and toxicity). It is fundamental to study representative preclinical tumor models that recapitulate patients with diseases (e.g., cancer) and evaluate the interplay between CMAs and the immune system, including the mononuclear phagocyte system (MPS), chemokines, hormones, and other immune modulators. Furthermore, standard allometric scaling using body weight does not accurately predict drug clearance in humans. Future studies are warranted to better understand the complex pharmacology and interaction of CMA carriers within individual preclinical models and their biological systems, such as the MPS and tumor microenvironment, and their application to allometric scaling across species. WIREs Nanomed Nanobiotechnol 2016, 8:642-653. doi: 10.1002/wnan.1394 For further resources related to this article, please visit the WIREs website. PMID:26846457

  16. Statistical optimization and anticancer activity of a red pigment isolated from Streptomyces sp. PM4

    Institute of Scientific and Technical Information of China (English)

    Valliappan Karuppiah; Chandramohan Aarthi; Kannan Sivakumar; Lakshmanan Kannan

    2013-01-01

    Objective: To enhance the pigment production by Streptomyces sp. PM4 for evaluating its anticancer activity. Methods:Response surface methodology was employed to enhance the production of red pigment from Streptomyces sp. PM4. Optimized pigment was purified and evaluated for the anticancer activity against HT1080, Hep2, HeLa and MCF7 cell lines by MTT assay. Results: Based on the response surface methodology, it could be concluded that maltose (4.06 g), peptone (7.34 g), yeast extract (4.34 g) and tyrosine (2.89 g) were required for the maximum production of pigment (1.68 g/L) by the Streptomyces sp. PM4. Optimization of the medium with the above tested features increased the pigment yield by 4.6 fold. Pigment showed the potential anticancer activity against HT1080, HEp-2, HeLa and MCF-7cell lines with the IC50 value of 18.5, 15.3, 9.6 and 8.5 respectively. Conclusions:The study revealed that the maximum amount of pigment could be produced to treat cancer.

  17. Synthesis and Evaluation of Some New Aza-B-homocholestane Derivatives as Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Yanmin Huang

    2014-03-01

    Full Text Available Using analogues of some marine steroidal oximes as precursors, a series of aza-B-homocholestane derivatives possessing different substituted groups at the 3-position of the steroidal nucleus were synthesized. Their biological activity against cancer cell proliferation was determined with multiple cancer cell lines. Aza-B-homocholestane derivatives possessing 3-hydroxyl, 3-hydroximino and 3-thiosemicarbazone groups displayed remarkable cytotoxicity to cancer cells via apoptosis inducing mechanism. Compounds 5, 10, 12, 15 and 18 exhibited better potency to inhibit cancer cell proliferation. In addition, compound 15 was further evaluated with three dimensional (3D multicellular spheroids assay to determine its potency against spheroid growth. The structure-activity relationship (SAR generated in the studies is valuable for the design of novel chemotherapeutic agents.

  18. Synthesis, molecular modeling, and biological evaluation of novel chiral thiosemicarbazone derivatives as potent anticancer agents.

    Science.gov (United States)

    Taşdemir, Demet; Karaküçük-İyidoğan, Ayşegül; Ulaşli, Mustafa; Taşkin-Tok, Tuğba; Oruç-Emre, Emİne Elçİn; Bayram, Hasan

    2015-02-01

    A series of new chiral thiosemicarbazones derived from homochiral amines in both enantiomeric forms were synthesized and evaluated for their in vitro antiproliferative activity against A549 (human alveolar adenocarcinoma), MCF-7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma), and HGC-27 (human stomach carcinoma) cell lines. Some of compounds showed inhibitory activities on the growth of cancer cell lines. Especially, compound exhibited the most potent activity (IC50 4.6 μM) against HGC-27 as compared with the reference compound, sindaxel (IC50 10.3 μM), and could be used as a lead compound to search new chiral thiosemicarbazone derivatives as antiproliferative agents. PMID:25399965

  19. Novel hederagenin-triazolyl derivatives as potential anti-cancer agents.

    Science.gov (United States)

    Rodríguez-Hernández, Diego; Demuner, Antonio J; Barbosa, Luiz C A; Heller, Lucie; Csuk, René

    2016-06-10

    A series of novel aryl-1H-1,2,3-triazol-4-yl methylester and amide derivatives of the natural product hederagenin was synthesized aiming to develop new antitumor agents, using Huisgen 1,3-dipolar cycloaddition reactions, with yields between 35% and 95%. The structures of all derivatives (2-31) were confirmed by MS, IR, (1)H NMR and (13)C NMR spectroscopic data. The cytotoxic activities of all compounds were screened against a panel of six human cancer cell lines using SRB assay. It was found that most of the compounds displayed higher levels of antitumor activities as compared to parent hederagenin. Compounds 4, 8 and 15 were the most potent against all human cancer cell lines. Furthermore, compound 11 was the most cytotoxic against cell HT29 showing EC50 = 1.6 μM and a selectivity index of 5.4. PMID:27017553

  20. Radiation Recall Reaction: Two Case Studies Illustrating an Uncommon Phenomenon Secondary to Anti-Cancer Agents

    International Nuclear Information System (INIS)

    Radiation recall phenomenon is a tissue reaction that develops throughout a previously irradiated area, precipitated by the administration of certain drugs. Radiation recall is uncommon and easily neglected by physicians; hence, this phenomenon is underreported in literature. This manuscript reports two cases of radiation recall. First, a 44-year-old man with nasopharyngeal carcinoma was treated with radiotherapy in 2010 and subsequently developed multi-site bone metastases. A few days after the docetaxel-based chemotherapy, erythema and papules manifested dermatitis, as well as swallowing pain due to pharyngeal mucositis, developed on the head and neck that strictly corresponded to the previously irradiated areas. Second, a 19-year-old man with recurrent nasal NK/T cell lymphoma initially underwent radiotherapy followed by chemotherapy after five weeks. Erythema and edema appeared only at the irradiated skin. Both cases were considered chemotherapeutic agents that incurred radiation recall reactions. Clinicians should be knowledgeable of and pay attention to such rare phenomenon

  1. Prevention of ocular toxicity by the intra-carotid perfusion of anticancer agents in the treatment of malignant glioma

    International Nuclear Information System (INIS)

    It is a problem of great concern to prevent ocular toxicity from complicating intra-carotid administration of lipophil anticancer agents. Attempts to prevent such a side effect were made during intra-carotid chemotherapy using remodeled catheter tips for epidural anesthesia. Twenty nine patients with malignant glioma received intra-carotid administration of neocarzinostatin (NCS). Six out of 17 patients (35.3 %) who received intra-carotid perfusion through an original catheter without a remodeled tip, developed ocular toxicity. The catheter tip remained proximal to the ophthalmic artery in all cases. On the other hand, 12 patients with a remodeled catheter tip did not develop ocular toxicity. In the latter group the tip of the catheter was located in the internal carotid artery sufficiently distal to the ophthalmic artery, or beyond the carotid bifurcation in 3 cases. Another advantage of the remodeled catheter was that the intra-carotid perfusion was feasible for a longer period with higher doses of NCS, than treatment with the commercial catheter for superselective embolization, which was found to be easily occluded and often ejected out of the carotid artery. Prior to and during the intra-carotid perfusion selective injection of Angiografin was performed through the catheter and the tumor was enhanced in the area of arterial supply, indicating the extent of chemotherapy and the degree of destruction of the blood-brain barrier. (author)

  2. Synthesis and biological evaluation of 12-N-p-chlorobenzyl sophoridinol derivatives as a novel family of anticancer agents.

    Science.gov (United States)

    Bi, Chongwen; Ye, Cheng; Li, Yinghong; Zhao, Wuli; Shao, Rongguang; Song, Danqing

    2016-05-01

    Taking 12-N-p-chlorobenzyl sophoridinol 2 as a lead, a series of novel sophoridinic derivatives with various 3'-substituents at the 11-side chain were synthesized and evaluated for their anticancer activity from sophoridine (1), a natural antitumor medicine. Among them, the sophoridinic ketones 5a-b, alkenes 7a-b and sophoridinic amines 14a-b displayed reasonable antiproliferative activity with IC50 values ranging from 3.8 to 5.4 μmol/L. Especially, compounds 5a and 7b exhibited an equipotency in both adriamycin (AMD)-susceptible and resistant MCF-7 breast carcinoma cells, indicating a different mechanism from AMD. The primary mechanism of action of 5a was to arrest the cell cycle at the G0/G1 phase, consistent with that of parent compound 1. Thus, we consider 12-chlorobenzyl sophoridinic derivatives with a tricyclic scaffold to be a new class of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells. PMID:27175333

  3. Pharmacognostic studies on Taxus baccata L.: A brilliant source of Anti-cancer agents.

    Science.gov (United States)

    Asif, Muhammad; Rizwani, Ghazala H; Zahid, Hina; Khan, Zahid; Qasim, Rao

    2016-01-01

    The present investigation was undertaken to establish standardization profile of Taxus baccata L. with the help of pharmacognostic parameters, which is not done before. T. baccata(Taxaceae), is native to Europe, is an evergreen needle-leaved tree, growing up to 28 m high. A large number of phytochemicals like taxoids viz. taxusin, baccatin, baccatin, lignans, flavanoids, steroids, paclitaxel and sugar derivatives have been isolated from it. For the treatment of different types of cancer like ovarian and breast cancers, Kaposi's sarcoma and lung cancers Paclitaxel (taxol) has been approved. Paclitaxel is also under clinical trial for remedy of number of other cancers in combination with other chemotherapeutic medications. Pharmacognostical and preliminary phytochemical screening of T. baccata will be useful to authenticate and avoid adulteration in the raw material. The diagnostic microscopic characters, physiochemical data and FTIR will be useful in the development of monograph. PMID:26826823

  4. DNA interaction studies of new nano metal based anticancer agent: validation by spectroscopic methods

    Science.gov (United States)

    Tabassum, Sartaj; Sharma, Girish Chandra; Arjmand, Farukh; Azam, Ameer

    2010-05-01

    A new nano dimensional heterobimetallic Cu-Sn containing complex as a potential drug candidate was designed, synthesized and characterized by analytical and spectral methods. The electronic absorption and electron paramagnetic resonance parameters of the complex revealed that the Cu(II) ion exhibits a square pyramidal geometry with the two pyrazole nitrogen atoms, the amine nitrogen atom and the carboxylate oxygen of the phenyl glycine chloride ligand located at the equatorial sites and the coordinated chloride ion occupying an apical position. 119Sn NMR spectral data showed a hexa-coordinated environment around the Sn(IV) metal ion. TEM, AFM and XRD measurements illustrate that the complex could induce the condensation of CT-DNA to a particulate nanostructure. The interaction of the Cu-Sn complex with CT-DNA was investigated by UV-vis absorption and emission spectroscopy, as well as cyclic voltammetric measurements. The results indicated that the complex interacts with DNA through an electrostatic mode of binding with an intrinsic binding constant Kb = 8.42 × 104 M - 1. The Cu-Sn complex exhibits effective cleavage of pBR322 plasmid DNA by an oxidative cleavage mechanism, monitored at different concentrations both in the absence and in the presence of reducing agents.

  5. DNA interaction studies of new nano metal based anticancer agent: validation by spectroscopic methods

    International Nuclear Information System (INIS)

    A new nano dimensional heterobimetallic Cu-Sn containing complex as a potential drug candidate was designed, synthesized and characterized by analytical and spectral methods. The electronic absorption and electron paramagnetic resonance parameters of the complex revealed that the Cu(II) ion exhibits a square pyramidal geometry with the two pyrazole nitrogen atoms, the amine nitrogen atom and the carboxylate oxygen of the phenyl glycine chloride ligand located at the equatorial sites and the coordinated chloride ion occupying an apical position. 119Sn NMR spectral data showed a hexa-coordinated environment around the Sn(IV) metal ion. TEM, AFM and XRD measurements illustrate that the complex could induce the condensation of CT-DNA to a particulate nanostructure. The interaction of the Cu-Sn complex with CT-DNA was investigated by UV-vis absorption and emission spectroscopy, as well as cyclic voltammetric measurements. The results indicated that the complex interacts with DNA through an electrostatic mode of binding with an intrinsic binding constant Kb = 8.42 x 104 M-1. The Cu-Sn complex exhibits effective cleavage of pBR322 plasmid DNA by an oxidative cleavage mechanism, monitored at different concentrations both in the absence and in the presence of reducing agents.

  6. Psoralea glandulosa as a Potential Source of Anticancer Agents for Melanoma Treatment

    Directory of Open Access Journals (Sweden)

    Alejandro Madrid

    2015-04-01

    Full Text Available With the aim of identifying novel agents with antigrowth and pro-apoptotic activity on melanoma cancer, the present study was undertaken to investigate the biological activity of the resinous exudate of aerial parts from Psoralea glandulosa, and its active components (bakuchiol (1, 3-hydroxy-bakuchiol (2 and 12-hydroxy-iso-bakuchiol (3 against melanoma cells (A2058. In addition, the effect in cancer cells of bakuchiol acetate (4, a semi-synthetic derivative of bakuchiol, was examined. The results obtained show that the resinous exudate inhibited the growth of cancer cells with IC50 value of 10.5 μg/mL after 48 h of treatment, while, for pure compounds, the most active was the semi-synthetic compound 4. Our data also demonstrate that resin is able to induce apoptotic cell death, which could be related to an overall action of the meroterpenes present. In addition, our data seem to indicate that the apoptosis correlated to the tested products appears, at least in part, to be associated with an increase of reactive oxygen species (ROS production. In summary, our study provides the first evidence that P. glandulosa may be considered a source of useful molecules in the development of analogues with more potent efficacy against melanoma cells.

  7. Mechanistic studies of cancer cell mitochondria- and NQO1-mediated redox activation of beta-lapachone, a potentially novel anticancer agent

    International Nuclear Information System (INIS)

    Beta-lapachone (beta-Lp) derived from the Lapacho tree is a potentially novel anticancer agent currently under clinical trials. Previous studies suggested that redox activation of beta-Lp catalyzed by NAD(P)H:quinone oxidoreductase 1 (NQO1) accounted for its killing of cancer cells. However, the exact mechanisms of this effect remain largely unknown. Using chemiluminescence and electron paramagnetic resonance (EPR) spin-trapping techniques, this study for the first time demonstrated the real-time formation of ROS in the redox activation of beta-lapachone from cancer cells mediated by mitochondria and NQO1 in melanoma B16–F10 and hepatocellular carcinoma HepG2 cancer cells. ES936, a highly selective NQO1 inhibitor, and rotenone, a selective inhibitor of mitochondrial electron transport chain (METC) complex I were found to significantly block beta-Lp meditated redox activation in B16–F10 cells. In HepG2 cells ES936 inhibited beta-Lp-mediated oxygen radical formation by ∼ 80% while rotenone exerted no significant effect. These results revealed the differential contribution of METC and NQO1 to beta-lapachone-induced ROS formation and cancer cell killing. In melanoma B16–F10 cells that do not express high NQO1 activity, both NOQ1 and METC play a critical role in beta-Lp redox activation. In contrast, in hepatocellular carcinoma HepG2 cells expressing extremely high NQO1 activity, redox activation of beta-Lp is primarily mediated by NQO1 (METC plays a minor role). These findings will contribute to our understanding of how cancer cells are selectively killed by beta-lapachone and increase our ability to devise strategies to enhance the anticancer efficacy of this potentially novel drug while minimizing its possible adverse effects on normal cells. - Highlights: • Both isolated mitochondria and purified NQO1 are able to generate ROS by beta-Lp. • The differential roles of mitochondria and NQO1 in mediating redox activation of beta-Lp • In cancer cells with

  8. Mechanistic studies of cancer cell mitochondria- and NQO1-mediated redox activation of beta-lapachone, a potentially novel anticancer agent

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jason Z. [Virginia Tech CRC, Blacksburg, VA (United States); Ke, Yuebin [Shenzhen Center for Disease Control and Prevention, Shenzhen 518055 (China); Misra, Hara P. [Virginia Tech CRC, Blacksburg, VA (United States); Trush, Michael A. [Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (United States); Li, Y. Robert [Campbell University School of Osteopathic Medicine, Buies Creek, NC (United States); Virginia Tech-Wake Forest University SBES, Blacksburg, VA (United States); Department of Biology, University of North Carolina at Greensboro, NC (United States); Zhu, Hong, E-mail: zhu@campbell.edu [Campbell University School of Osteopathic Medicine, Buies Creek, NC (United States); Jia, Zhenquan, E-mail: z_jia@uncg.edu [Department of Biology, University of North Carolina at Greensboro, NC (United States)

    2014-12-15

    Beta-lapachone (beta-Lp) derived from the Lapacho tree is a potentially novel anticancer agent currently under clinical trials. Previous studies suggested that redox activation of beta-Lp catalyzed by NAD(P)H:quinone oxidoreductase 1 (NQO1) accounted for its killing of cancer cells. However, the exact mechanisms of this effect remain largely unknown. Using chemiluminescence and electron paramagnetic resonance (EPR) spin-trapping techniques, this study for the first time demonstrated the real-time formation of ROS in the redox activation of beta-lapachone from cancer cells mediated by mitochondria and NQO1 in melanoma B16–F10 and hepatocellular carcinoma HepG2 cancer cells. ES936, a highly selective NQO1 inhibitor, and rotenone, a selective inhibitor of mitochondrial electron transport chain (METC) complex I were found to significantly block beta-Lp meditated redox activation in B16–F10 cells. In HepG2 cells ES936 inhibited beta-Lp-mediated oxygen radical formation by ∼ 80% while rotenone exerted no significant effect. These results revealed the differential contribution of METC and NQO1 to beta-lapachone-induced ROS formation and cancer cell killing. In melanoma B16–F10 cells that do not express high NQO1 activity, both NOQ1 and METC play a critical role in beta-Lp redox activation. In contrast, in hepatocellular carcinoma HepG2 cells expressing extremely high NQO1 activity, redox activation of beta-Lp is primarily mediated by NQO1 (METC plays a minor role). These findings will contribute to our understanding of how cancer cells are selectively killed by beta-lapachone and increase our ability to devise strategies to enhance the anticancer efficacy of this potentially novel drug while minimizing its possible adverse effects on normal cells. - Highlights: • Both isolated mitochondria and purified NQO1 are able to generate ROS by beta-Lp. • The differential roles of mitochondria and NQO1 in mediating redox activation of beta-Lp • In cancer cells with

  9. Clinical status of anti-cancer agents derived from marine sources.

    Science.gov (United States)

    Singh, Ram; Sharma, Mukul; Joshi, Penny; Rawat, Diwan S

    2008-08-01

    The chemical, biological and ecological diversity of the marine ecosystem has contributed immensely in the discovery of extremely potent compounds that have shown potent activities in antitumor, analgesia, antiinflammatory, immunomodulation, allergy, anti-viral etc. The compounds of marine origin are diverse in structural class from simple linear peptides to complex macrocyclic polyethers. The recent advances in the sophisticated instruments for the isolation and characterization of marine natural products and development of high-throughput screening, have substantially increased the rate of discovery of various compounds of biomedical application. Didemnin was the first marine peptide that entered in human clinical trials in US for the treatment of cancer and other compounds such as dolastatin-10, soblidotin, didemnin B, ecteinascidin 743, girolline, aplidine, cryptophycins (also arenastatin A), bryostatin 1, ILX 651, kahalalide F, E7389, discodermolide, ES-285 (spisulosine), HTI-286 (hemiasterlin derivative), squalamine, KRN-7000, vitilevuamide, Laulimalide, Curacin A, diazonamide, peloruside A, eleutherobin, sarcodictyin, thiocoraline, salicylihalimides A, ascididemnin, CGX-1160, CGX-1007dictyodendrins, GTS-21 (aka DMBX), manoalide, IPL-576,092 (aka HMR-4011A) have entered in the clinical trials. This article summarize clinical status and synthetic advances of some of these compounds. PMID:18690825

  10. Bacterial biosynthesis and maturation of the didemnin anti-cancer agents

    KAUST Repository

    Xü, Ying

    2012-05-23

    The anti-neoplastic agent didemnin B from the Caribbean tunicate Trididemnum solidum was the first marine drug to be clinically tested in humans. Because of its limited supply and its complex cyclic depsipeptide structure, considerable challenges were encountered during didemnin B\\'s development that continue to limit aplidine (dehydrodidemnin B), which is currently being evaluated in numerous clinical trials. Herein we show that the didemnins are bacterial products produced by the marine α-proteobacteria Tistrella mobilis and Tistrella bauzanensis via a unique post-assembly line maturation process. Complete genome sequence analysis of the 6,513,401 bp T. mobilis strain KA081020-065 with its five circular replicons revealed the putative didemnin biosynthetic gene cluster (did) on the 1,126,962 bp megaplasmid pTM3. The did locus encodes a 13-module hybrid non-ribosomal peptide synthetase-polyketide synthase enzyme complex organized in a collinear arrangement for the synthesis of the fatty acylglutamine ester derivatives didemnins X and Y rather than didemnin B as first anticipated. Imaging mass spectrometry of T. mobilis bacterial colonies captured the time-dependent extracellular conversion of the didemnin X and Y precursors to didemnin B, in support of an unusual post-synthetase activation mechanism. Significantly, the discovery of the didemnin biosynthetic gene cluster may provide a long-term solution to the supply problem that presently hinders this group of marine natural products and pave the way for the genetic engineering of new didemnin congeners. © 2012 American Chemical Society.

  11. Isolation of Cannabinoids from the plant Cannabis sativa and its potential anticancer activity

    OpenAIRE

    Tariq A.L.; Reyaz A.L

    2012-01-01

    The plant leaves were identified as Cannabis sativa L. The cannabniods were extracted by aqueous extract found a total yield of 3.8g while as acetone extract 4.8g. The protein content in crude extract of Cannabis sativa L for aqeous extract found 112μg/ml and for acetone extract 160μg/ml. The molecular weight of protein by SDS PGAGE found to be 70KDa. The HPLC intension percentage for aqueous was 11 while for acetone extract it found 25. The actone extract exhibited more anticancer activity a...

  12. Isolation of Cannabinoids from the plant Cannabis sativa and its potential anticancer activity

    Directory of Open Access Journals (Sweden)

    Tariq. A. L

    2012-03-01

    Full Text Available The plant leaves were identified as Cannabis sativa L. The cannabniods were extracted by aqueous extract found a total yield of 3.8g while as acetone extract 4.8g. The protein content in crude extract of Cannabis sativa L for aqeous extract found 112μg/ml and for acetone extract 160μg/ml. The molecular weight of protein by SDS PGAGE found to be 70KDa. The HPLC intension percentage for aqueous was 11 while for acetone extract it found 25. The actone extract exhibited more anticancer activity against HT29, MCF7 and SF-26 Cells

  13. Xanthatin and xanthinosin from the burs of Xanthium strumarium L. as potential anticancer agents.

    Science.gov (United States)

    Ramírez-Erosa, Irving; Huang, Yaoge; Hickie, Robert A; Sutherland, Ronald G; Barl, Branka

    2007-11-01

    Xanthatin and xanthinosin, 2 sesquiterpene lactones isolated from the burs of Xanthiun strumarium L. (cocklebur), showed moderate to high in vitro cytotoxic activity in the human cancer cell lines WiDr ATCC (colon), MDA-MB-231 ATCC (breast), and NCI-417 (lung). Xanthatin and xanthinosin were purified as the result of a multi-screening bioassay-guided study of wild plant species of the family Asteraceae, collected from various sites in Saskatchewan, Canada. Seventy-five extracts at a single concentration of 100 microg/mL were evaluated for in vitro cytotoxicity to the human cancer cell lines used. The chloroform extract of Carduus nutans L. (nodding thistle) aerial parts (IC50, 9.3 microg/mL) and the hexane extract of Echinacea angustifolia DC. (narrow-leaved purple coneflower) root (IC50, 4.0 microg/mL) were moderately to highly cytotoxic to the lung cancer cell line. The chloroform extracts of X. strumarium L. burs and Tanacetum vulgare L. (tansy) aerial parts exhibited the highest cytotoxicity for all cell lines tested; their IC50 values, obtained from multidose testing, ranged from 0.1 to 6.2 microg/mL (X. strumarium) and from 2.4 to 9.1 microg/mL (T. vulgare). Further purification of the chloroform fraction of X. strumarium yielded xanthatin and xanthinosin in high yields. This is the first time that these compounds have been reported in the burs of X. strumarium. Their IC50 values are also reported herein. PMID:18066118

  14. Fucoidan Extract Enhances the Anti-Cancer Activity of Chemotherapeutic Agents in MDA-MB-231 and MCF-7 Breast Cancer Cells

    OpenAIRE

    Zhongyuan Zhang; Kiichiro Teruya; Toshihiro Yoshida; Hiroshi Eto; Sanetaka Shirahata

    2013-01-01

    Fucoidan, a fucose-rich polysaccharide isolated from brown alga, is currently under investigation as a new anti-cancer compound. In the present study, fucoidan extract (FE) from Cladosiphon navae-caledoniae Kylin was prepared by enzymatic digestion. We investigated whether a combination of FE with cisplatin, tamoxifen or paclitaxel had the potential to improve the therapeutic efficacy of cancer treatment. These co-treatments significantly induced cell growth inhibition, apoptosis, as well as ...

  15. Citotoxicidad y actividad anticancerígena de dos flavonoides aislados y purificados de Brownea ariza Brenth Cytotoxicity and anticarcinogenic activity of two flavonoids isolated and purified from Brownea ariza Brenth

    Directory of Open Access Journals (Sweden)

    Juan F GIL R

    2009-01-01

    Full Text Available La creciente resistencia a agentes anticancerígenos ha volcado la ciencia médica y farmacológica hacia la búsqueda de nuevos compuestos con estas características, en este campo los productos naturales tienen gran relevancia por la actividad antitumoral mostrada por muchos de ellos. Los flavonoides son metabolitos secundarios que tienen reportada actividad anticancerígena y pueden convertirse en fuente importante para tratar el cáncer; por esto se pretende aislar flavonoides de Brownea ariza Brenth, determinar su estructura y evaluar su actividad antitumoral. Los análisis fitoquímicos de las hojas de Brownea ariza Brenth (Caesalpiniaceae permiten aislar un flavonol identificado como (1, y un glicósido de flavonol, Quercitrina (2. Las estructuras se determinan por técnicas espectroscópicas: UV-Vis con reactivos de desplazamiento; RMN 1D y 2D (¹H, 13C, COSY, DEPT, HMBC; HMQC, y espectrometría de masas. Se evalúa la actividad citotóxica en línea celular VERO (ATCC:CCL-81 y la actividad anticancerígena en Mieloma Murino SP2/0-Ag14 (ATCC:CRL-1581, realizando conteo de células viables por exclusión con azul Tripan, obteniéndose una concentración citotóxica media para (1 de 300 μg/mL y no determinada para (2 en las concentraciones trabajadas; la actividad anticancerígena para (1 tiene una concentración efectiva media de 150 μg/mLy no determinada para (2 en las concentraciones trabajadas.The growing resistance to anticancer agents has turned medical science and pharmacology towards finding new compounds with these characteristics; in this area the natural products have great relevance, since many of these have anticancer activity. Flavonoids as secondary metabolites have reported anti-tumor activity and can become important source for cancer treatment; why search isolate flavonoids Brownea ariza Brenth to evaluate their anticancer activity. The Phytochemical analysis of leaves of Brownea ariza Brenth. (Caesalpiniaceae let

  16. The zebrafish embryo as a tool for screening and characterizing pleurocidin host-defense peptides as anti-cancer agents

    OpenAIRE

    Michael G. Morash; Douglas, Susan E.; Anna Robotham; Ridley, Christina M.; Gallant, Jeffrey W.; Soanes, Kelly H.

    2011-01-01

    SUMMARY The emergence of multidrug-resistant cancers and the lack of targeted therapies for many cancers underscore an unmet need for new therapeutics with novel modes of action towards cancer cells. Host-defense peptides often exhibit selective cytotoxicity towards cancer cells and show potential as anti-cancer therapeutics. Here, we screen 26 naturally occurring variants of the peptide pleurocidin for cytotoxic and anti-cancer activities, and investigate the underlying mechanism of action. ...

  17. The zebrafish embryo as a tool for screening and characterizing pleurocidin host-defense peptides as anti-cancer agents

    OpenAIRE

    Morash, Michael G.; Douglas, Susan E.; Anna Robotham; Ridley, Christina M.; Gallant, Jeffrey W.; Soanes, Kelly H.

    2011-01-01

    SUMMARY The emergence of multidrug-resistant cancers and the lack of targeted therapies for many cancers underscore an unmet need for new therapeutics with novel modes of action towards cancer cells. Host-defense peptides often exhibit selective cytotoxicity towards cancer cells and show potential as anti-cancer therapeutics. Here, we screen 26 naturally occurring variants of the peptide pleurocidin for cytotoxic and anti-cancer activities, and investigate the underlying mechanism of actio...

  18. Synthesis of 1-benzyl-3-(5-hydroxymethyl-2-furyl)selenolo[3,2-c]pyrazole derivatives as new anticancer agents.

    Science.gov (United States)

    Chou, Li-Chen; Huang, Li-Jiau; Hsu, Mei-Hua; Fang, Mei-Chi; Yang, Jai-Sing; Zhuang, Shi-Hong; Lin, Hui-Yi; Lee, Fang-Yu; Teng, Che-Ming; Kuo, Sheng-Chu

    2010-04-01

    As part of our continuing search for potential anticancer drug candidates among YC-1 analogs, 1, 3-disubstituted selenolo[3,2-c]pyrazole derivatives were synthesized and evaluated for their cytotoxicity against NCI-H226 non-small cell lung cancer and A-498 renal cancer cell lines. Significant cytotoxicity was observed in 3-(5-hydroxymethyl-2-furyl) derivatives (2, 33, 36 and 37). Among them, compound 2 was found to have the most potent activity. The mode of action of compound 2 seems to differ from those of the 175 anticancer agents listed in NCI's standard database and resembles that of YC-1. Thus, we recommend that compound 2 should be developed further as new drug candidate for treatment of non-small cell lung cancer and renal cancer. PMID:20097456

  19. Synthesis and in vitro evaluation of novel triazine analogues as anticancer agents and their interaction studies with bovine serum albumin.

    Science.gov (United States)

    Singla, Prinka; Luxami, Vijay; Paul, Kamaldeep

    2016-07-19

    A novel series of triazine-benzimidazole analogs has been designed and synthesized for their in vitro anticancer activities. Four compounds (6, 16, 17 and 20) were identified as highly potent anticancer agents against 60 human cancer cell lines with GI50 in the nanomolar range. To improve the drug applications toward cancer cells, there is a need to couple these compounds to some carrier macromolecules. Following this approach, the interaction between triazine-benzimidazole analogues and bovine serum albumin (BSA) has been investigated with UV-Visible and fluorescence spectroscopic methods under physiological conditions. The observed fluorescence quenching indicates that these compounds could efficiently bind with BSA and be transported to the target site. PMID:27089212

  20. ISOLATION AND CHARACTERIZATION OF BIOACTIVE PROTEIN FROM GREEN ALGAE Turbinaria decurrens AS ANTIBACTERIAL AND ANTICANCER AGENT

    OpenAIRE

    Seniwati Dali; Hasnah Natsir; Hanapi Usman

    2013-01-01

    A research on the ability of protein fraction from green algae Turbinaria decurrens in territorial of South Sulawesi to inhibit the growth of Salmonella thypi and Staphylococcus aureus has been conducted. Proteins was fractionated from the crude extract using salting out method with 0-20%, 20-40%, 40-60% and 60-80% ammonium sulphate saturation. Protein was purified by a dialysis method using a selophan membrane. The protein level was determined by a Lowry method, the highest protein concentr...

  1. ISOLATION AND CHARACTERIZATION OF BIOACTIVE PROTEIN FROM GREEN ALGAE Turbinaria decurrens AS ANTIBACTERIAL AND ANTICANCER AGENT

    OpenAIRE

    Seniwati Dali; Hasnah Natsir; Hanapi Usman

    2011-01-01

    A research on the ability of protein fraction from green algae Turbinaria decurrens in territorial of South Sulawesi to inhibit the growth of Salmonella thypi and Staphylococcus aureus has been conducted. Proteins was fractionated from the crude extract using salting out method with 0-20%, 20-40%, 40-60% and 60-80% ammonium sulphate saturation. Protein was purified by a dialysis method using a selophan membrane. The protein level was determined by a Lowry method, the highest protein concentr...

  2. Pharmacokinetics and pharmacodynamics of phase II drug metabolizing/antioxidant enzymes gene response by anticancer agent sulforaphane in rat lymphocytes.

    Science.gov (United States)

    Wang, Hu; Khor, Tin Oo; Yang, Qian; Huang, Ying; Wu, Tien-Yuan; Saw, Constance Lay-Lay; Lin, Wen; Androulakis, Ioannis P; Kong, Ah-Ng Tony

    2012-10-01

    This study assesses the pharmacokinetics (PK) and pharmacodynamics (PD) of Nrf2-mediated increased expression of phase II drug metabolizing enzymes (DME) and antioxidant enzymes which represents an important component of cancer chemoprevention in rat lymphocytes following intravenous (iv) administration of an anticancer phytochemical sulforaphane (SFN). SFN was administered intravenously to four groups of male Sprague-Dawley JVC rats each group comprising four animals. Blood samples were drawn at selected time points. Plasma were obtained from half of each of the blood samples and analyzed using a validated LC-MS/MS method. Lymphocytes were collected from the remaining blood samples using Ficoll-Paque Plus centrifuge medium. Lymphocyte RNAs were extracted and converted to cDNA, quantitative real-time PCR analyses were performed, and fold changes were calculated against those at time zero for the relative expression of Nrf2-target genes of phase II DME/antioxidant enzymes. PK-PD modeling was conducted based on Jusko's indirect response model (IDR) using GastroPlus and bootstrap method. SFN plasma concentration declined biexponentially and the pharmacokinetic parameters were generated. Rat lymphocyte mRNA expression levels showed no change for GSTM1, SOD, NF-κB, UGT1A1, or UGT1A6. Moderate increases (2-5-fold) over the time zero were seen for HO-1, Nrf2, and NQO1, and significant increases (>5-fold) for GSTT1, GPx1, and Maf. PK-PD analyses using GastroPlus and the bootstrap method provided reasonable fitting for the PK and PD profiles and parameter estimates. Our present study shows that SFN could induce Nrf2-mediated phase II DME/antioxidant mRNA expression for NQO1, GSTT1, Nrf2, GPx, Maf, and HO-1 in rat lymphocytes after iv administration, suggesting that Nrf2-mediated mRNA expression in lymphocytes may serve as surrogate biomarkers. The PK-PD IDR model simultaneously linking the plasma concentrations of SFN and the PD response of lymphocyte mRNA expression is

  3. Anticancer chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1988-10-01

    Despite troubled beginnings, anticancer chemotherapy has made significant contribution to the control of cancer in man, particularly within the last two decades. Early conceptual observations awakened the scientific community to the potentials of cancer chemotherapy. There are now more than 50 agents that are active in causing regression of clinical cancer. Chemotherapy's major conceptual contributions are two-fold. First, there is now proof that patients with overt metastatic disease can be cured, and second, to provide a strategy for control of occult metastases. In man, chemotherapy has resulted in normal life expectancy for some patients who have several types of metastatic cancers, including choriocarcinoma, Burkitt's lymphomas, Wilm's tumor, acute lymphocytic leukemia, Hodgkins disease, diffuse histiocytic lymphoma and others. Anticancer chemotherapy in Veterinary medicine has evolved from the use of single agents, which produce only limited remissions, to the concept of combination chemotherapy. Three basic principles underline the design of combination chemotherapy protocols; the fraction of tumor cell killed by one drug is independent of the fraction killed by another drug; drugs with different mechanisms of action should be chosen so that the antitumor effects will be additive; and since different classes of drugs have different toxicities the toxic effects will not be additive.

  4. Screening the yeast genome for energetic metabolism pathways involved in a phenotypic response to the anti-cancer agent 3-bromopyruvate

    OpenAIRE

    Lis, Paweł; Jurkiewicz, Paweł; Cal-Bąkowska, Magdalena; Ko, Young H.; Pedersen, Peter L.; Goffeau, Andre; Ułaszewski, Stanisław

    2016-01-01

    In this study the detailed characteristic of the anti-cancer agent 3-bromopyruvate (3-BP) activity in the yeast Saccharomyces cerevisiae model is described, with the emphasis on its influence on energetic metabolism of the cell. It shows that 3-BP toxicity in yeast is strain-dependent and influenced by the glucose-repression system. Its toxic effect is mainly due to the rapid depletion of intracellular ATP. Moreover, lack of the Whi2p phosphatase results in strongly increased sensitivity of y...

  5. Kinetics and thermochemistry of hydrolysis mechanism of a novel anticancer agent trans-[PtCl2(dimethylamine)(isopropylamine)]: A DFT study

    Science.gov (United States)

    Hussain, Iftikar; Gour, N. K.; Deka, Ramesh Ch.

    2016-05-01

    Theoretical investigation has been made on the hydrolysis mechanism of a novel transplatin anticancer agent trans-[PtCl2(dimethylamine)(isopropylamine)] in gas as well as aqueous phases using DFT method. The transition state geometries along with other stationary points on potential energy surface are optimized and characterized. The calculated activation barrier and the predicted relative free energies for the two successive steps are in good agreement with the experimental data reported in the literature. The rate constants are calculated using Eyring equation and results show that the second step is the rate-limiting process having higher activation energy compared to that of the first step.

  6. CYP3A4 overexpression enhances apoptosis induced by anticancer agent imidazoacridinone C-1311, but does not change the metabolism of C-1311 in CHO cells

    OpenAIRE

    Pawłowska, Monika; Augustin, Ewa; Mazerska, Zofia

    2013-01-01

    Aim: To examine whether CYP3A4 overexpression influences the metabolism of anticancer agent imidazoacridinone C-1311 in CHO cells and the responses of the cells to C-1311. Methods: Wild type CHO cells (CHO-WT), CHO cells overexpressing cytochrome P450 reductase (CPR) [CHO-HR] and CHO cells coexpressing CPR and CYP3A4 (CHO-HR-3A4) were used. Metabolic transformation of C-1311 and CYP3A4 activity were measured using RP-HPLC. Flow cytometry analyses were used to examine cell cycle, caspase-3 act...

  7. Anticancer Effect of Rutin Isolated from the Methanolic Extract of Triticum aestivum Straw in Mice

    OpenAIRE

    Savita Dixit

    2014-01-01

    Rutin is the bioactive flavanoid isolated from the straw part of Triticum aestivum and possess various pharmacological applications. The aim of this study is to evaluate the chemopreventive potential of rutin in an experimental skin carcinogenesis mice model system. Skin tumor was induced by topical application of 7,12-dimethyl benz(a) anthracene (DMBA) and promoted by croton oil in Swiss albino mice. To assess the chemopreventive potential of rutin, it was orally administered at a concentrat...

  8. Synthesis and evaluation of multi-wall carbon nanotube–paclitaxel complex as an anti-cancer agent

    Science.gov (United States)

    Ghasemvand, Fariba; Biazar, Esmaeil; Tavakolifard, Sara; Khaledian, Mohammad; Rahmanzadeh, Saeid; Momenzadeh, Daruosh; Afroosheh, Roshanak; Zarkalami, Faezeh; Shabannezhad, Marjan; Hesami Tackallou, Saeed; Massoudi, Nilofar; Heidari Keshel, Saeed

    2016-01-01

    Aim: The aim of this study was to design multi-walled carbon nanotubes (MWCNTs) loaded with paclitaxel (PTX) anti-cancer drug and investigate its anti-cancerous efficacy of human gastric cancer. Background: Carbon nanotubes (CNTs) represent a novel nano-materials applied in various fields such as drug delivery due to their unique chemical properties and high drug loading. Patients and methods: In this study, multi-walled carbon nanotubes (MWCNTs) pre-functionalized covalently with a paclitaxel (PTX) as an anti-cancer drug and evaluated by different analyses including, scanning electron microscope (SEM), particle size analyzer and cellular analyses. Results: A well conjugated of anti-cancer drug on the carbon nanotube surfaces was shown. This study demonstrates that the MWCN-PTX complex is a potentially useful system for delivery of anti-cancer drugs. The flow cytometry, CFU and MTT assay results have disclosed that MWCNT/PTXs might promote apoptosis in MKN-45 gastric adenocarcinoma cell line. Conclusion: According to results, our simple method can be designed a candidate material for chemotherapy. It has presented a few bio-related applications including, their successful use as a nano-carriers for drug transport. PMID:27458512

  9. N-Phenyl-2-p-tolylthiazole-4-carboxamide derivatives: Syn-thesis and cytotoxicity evaluation as anticancer agents

    Directory of Open Access Journals (Sweden)

    Ahmad Mohammadi-Farani

    2014-07-01

    Conclusion: A new series of phenylthiazole derivatives were synthesized and their anticancer activity was assessed against cancerous cell lines. More structural modifications and derivatization is necessary to achieve to the more potent compounds.       

  10. Vitamin E analogs, a novel group of "mitocans," as anticancer agents: The importance of being redox-silent

    Czech Academy of Sciences Publication Activity Database

    Neužil, Jiří; Tomasetti, M.; Zhao, Y.; Dong, L.F.; Birringer, M.; Wang, X. F.; Low, P.; Wu, K.; Salvatore, B.A.; Ralph, S.J.

    2007-01-01

    Roč. 71, č. 5 (2007), s. 1185-1199. ISSN 0026-895X Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50520701 Keywords : vitamin E analogs * redox-silence * anticancer drugs Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.622, year: 2007

  11. External influences and priority-setting for anti-cancer agents: a case study of media coverage in adjuvant trastuzumab for breast cancer

    Directory of Open Access Journals (Sweden)

    Fralick John

    2007-06-01

    Full Text Available Abstract Background Setting priorities for the funding of new anti-cancer agents is becoming increasingly complex. The funding of adjuvant trastuzumab for breast cancer has brought this dilemma to the fore. In this paper we review external factors that may influence decision-making bodies and present a case study of media response in Ontario, Canada to adjuvant trastuzumab for breast cancer. Methods A comprehensive search of the databases of Canadian national and local newspapers and television was performed. Articles pertaining to trastuzumab in adjuvant breast cancer as well as 17 other anti-cancer drugs and indications were retrieved. The search period was from the date when individual trial results were announced to the date funding was made available in Ontario. Results During the 2.6 months between the release of the trastuzumab results to funding approval in Ontario, we identified 51 episodes of media coverage. For the 17 other drugs/indications (7 breast and 10 non-breast, the median time to funding approval was 31 months (range 14–46. Other recent major advances in oncology such as adjuvant vinorelbine/cisplatin for resected NSCLC and docetaxel for advanced prostate cancer received considerably less media attention (17 media reports for each than trastuzumab. The median number of media reports for breast cancer drugs was 4.5 compared to 2.5 for non-breast cancer drugs (p = 0.56. Conclusion Priority-setting for novel anti-cancer agents is a complex process that tries to ensure fair use of constrained resources to fund therapies with the best evidence of clinical benefit. However, this process is subject to external factors including the influence of media, patient advocates, politicians, and industry. The data in this case study serve to illustrate the significant involvement one (or all of these external factors may play in the debate over priority-setting.

  12. [Response of Pharmaceutical Companies to the Crisis of Post-Marketing Clinical Trials of Anti-Cancer Agents -- Results of Questionnaires to Pharmaceutical Companies].

    Science.gov (United States)

    Nakajima, Toshifusa

    2016-04-01

    Investigator-oriented post-marketing clinical trials of anti-cancer agents are faced to financial crisis due to drastic decrease in research-funds from pharmaceutical companies caused by a scandal in 2013. In order to assess the balance of research funds between 2012 and 2014, we made queries to 26 companies manufacturing anti-cancer agents, and only 10 of 26 responded to our queries. Decrease in the fund was observed in 5 of 10, no change in 1, increase in 3 and no answer in 1. Companies showed passive attitude to carry out doctor-oriented clinical trials of off-patent drugs or unapproved drugs according to advanced medical care B program, though some companies answered to proceed approved routines of these drugs if clinical trials showed good results. Most companies declined to make comments on the activity of Japan Agency for Medical Research and Development (AMED), but some insisted to produce good corroboration between AMED and pharmaceutical companies in order to improve the quality of trials. Further corroboration must be necessary for this purpose among researchers, governmental administrative organs, pharmaceutical companies, patients' groups, and mass-media. PMID:27220801

  13. Anticancer effect of two diterpenoid compounds isolated from Annona glabra Linn

    Institute of Scientific and Technical Information of China (English)

    Yong-hong ZHANG; Hai-yan PENG; Guo-hao XIA; Ming-yan WANG; Ying HAN

    2004-01-01

    AIM: To study the inhibitory effect of two diterpenoid compounds isolated from Annona glabra Linn (Cunabic acid and ent-kauran-19-al-17-oic acid) on the proliferation of Human Liver Cancer (HLC) cell line SMMC-7721 and its mechanism. METHODS: Inhibition of cell proliferation was measured by MTT assay. The morphological changes of SMMC-7721 cells were observed under inverted phase-contrast microscope, fluorescent microscope,transmission electron microscope (TEM), and scanning electron microscope (SEM). Flow cytometer (FCM) was used to calculate the cell apoptotic rate, and immunohistochemical staining was used to observe the regulation of gene expression. RESULTS: The proliferation of SMMC-7721 cells was obviously inhibited after being treated with Cunabic acid at the concentration >5 μmol/L and ent-kauran-19-al-17-oic acid >10 μmol/L. The biggest inhibitory effect was 81.05 % when treated with Cunabic acid at the concentration of 25 μmol/L. The effect had a linear relationship with concentration. The result indicated that drug-treated cells exhibit typical morphological changes of apoptosis, including condensed chromatin and a reduction in volume. Sub-G0/G1 peak was found by FCM analysis and the cell cycle was arrested at G0/G1 stage. The apoptotic rates of the cells treated by Cunabic acid and ent-kauran-19-al-17-oic acid were 43.31% and 24.95 %, respectively. It was visualized by immunohistochemical staining that the d.rugs down-regulated the gene expression of bcl-2 gene and up-regulated that of bax gene. CONCLUSION: The two diterpenoid compounds isolated from Annona glabra Linn, Cunabic acid and entkauran-19-al-17-oic acid can obviously inhibit the proliferation of HLC cell line SMMC-7721. The mechanism is correlated with the induction of cell apoptosis by down-regulating the gene expression of bcl-2 gene and upregulating that of bax gene.

  14. Design, Synthesis and Biological Evaluation of Novel Bromophenol Derivatives Incorporating Indolin-2-One Moiety as Potential Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Li-Jun Wang

    2015-02-01

    Full Text Available A series of bromophenol derivatives containing indolin-2-one moiety were designed and evaluated that for their anticancer activities against A549, Bel7402, HepG2, HeLa and HCT116 cancer cell lines using MTT assay in vitro. Among them, seven compounds (4g–4i, 5h, 6d, 7a, 7b showed potent activity against the tested five human cancer cell lines. Wound-healing assay demonstrated that compound 4g can be used as a potent compound for inactivating invasion and metastasis by inhibiting the migration of cancer cells. The structure–activity relationships (SARs of bromophenol derivatives had been discussed, which were useful for exploring and developing bromophenol derivatives as novel anticancer drugs.

  15. Synthesis, biological evaluation and molecular docking studies of some novel cyclopropane carbohydrazide derivatives as potential anticancer agents

    Indian Academy of Sciences (India)

    PONNAPALLI VEERABHADRA SWAMY; PULLAIAH CHINA KAMBHAMPATI; KOTHAPALLI BONNOTH CHANDRASEKHAR; GUGULOTHU THIRUPATHI; POMBALA SUJITHA; CHITYAL GANESH KUMAR; VEERAMACHANENI GANESH KUMAR

    2016-06-01

    The synthesis of novel series of cyclopropane carbohydrazides is described via Knoevenagel condensationof 2-furfuraldehyde with malonic acid in five steps. Condensation of the key intermediate 2-(furan-2-yl)cyclopropanecarbohydrazide (4) with heteroaryl/aryl aldehydes (a-t) in presence of ZnO NP in ethanolresulted in substituted N- hetero/arylidene-2-(furan-2-yl) cyclopropane carbohydrazides (5a-t). These compoundswere screened for their anticancer activity against a panel of four cancer cell lines and four compoundsshowed promising activity at micromolar concentration against all the tested cell lines with IC50 values rangingbetween 1.9-8.45μM. These compounds were further validated with in silico methods at the anticancer target,colchicine binding site.

  16. Studies of the effect on the cell cycle and of the radiosensitization of a novel anti-cancer agent TZT-1027

    International Nuclear Information System (INIS)

    The anticancer agent TZT-1027, an analog of dolastatin 10 originated from a marine organism, is an anti-microtubule agent and the present studies were performed to elucidate its activities in the title. Cell cycle analysis was done in mouse breast carcinoma tsFT210 cell line by flow-cytometry, which revealed that TZT-1027 specifically acted at G2/M, the stage most sensitive to radiation. Human non-small cell lung cancer H460 cell line was used for clonogenic assay: the dose enhancement factor at survival 0.1, estimated by the survival curve of cells irradiated by 60Co gamma ray at 0-6 Gy with or without TZT-1027, was found to be 1.2, which revealed the enhancement of radiosenstivity. In addition, their radiation-induced apoptosis was found to be also enhanced by the agent. When nude-mice transplanted with H460 cells were treated with TZT-1027 and 60Co gamma ray at 10 Gy, radiosensitization and apoptosis enhancement by the agent were also clear in vivo. Thus, TZT-1027 enhances the anti-tumor effect of radiation and this radiosensitizing mechanism involves the apoptotic process at least partly, both of which are conceivably the basis of future clinical trial of the agent. (T.I.)

  17. Liquid Chromatography - Triple Quadrupole Mass Spectrometry : The gold standard for quantitative bioanalysis of anti-cancer agents

    OpenAIRE

    Vainchtein, L.D.

    2008-01-01

    To understand the pharmacologic mechanisms of action, efficacy and toxicity of any anti-cancer drug it is important to know how the compound is transformed in the body: either into active metabolites or inactive and toxic (degradation) products. This information may lead to the success or failure of a drug in arresting cancer cell growth, and facilitates the design of more effective drugs. To quantify the drug and to follow its absorption, distribution, metabolism, and elimination (ADME) in b...

  18. Synthesis of Rapamycin Derivatives Containing the Triazole Moiety Used as Potential mTOR-Targeted Anticancer Agents.

    Science.gov (United States)

    Xie, Lijun; Huang, Jie; Chen, Xiaoming; Yu, Hui; Li, Kualiang; Yang, Dan; Chen, Xiaqin; Ying, Jiayin; Pan, Fusheng; Lv, Youbing; Cheng, Yuanrong

    2016-06-01

    Rapamycin, a potent antifungal antibiotic, was approved as immunosuppressant, and lately its derivatives have been developed into mTOR targeting anticancer drugs. Structure modification was performed at the C-42 position of rapamycin, and a novel series of rapamycin triazole hybrids (4a-d, 5a-e, 8a-e, and 9a-e) was facilely synthesized via Huisgen's reaction. The anticancer activity of these compounds was evaluated against the Caski, H1299, MGC-803, and H460 human cancer cell lines. Some of the derivatives (8a-e, 9a-e) appeared to have stronger activity than that of rapamycin; however, 4a-d and 5a-e failed to show potential anticancer activity. Compound 9e with a (2,4-dichlorophenylamino)methyl moiety on the triazole ring was the most active anticancer compound, which showed IC50 values of 6.05 (Caski), 7.89 (H1299), 25.88 (MGC-803), and 8.60 μM (H460). In addition, research on the mechanism showed that 9e was able to cause cell morphological changes and to induce apoptosis in the Caski cell line. Most importantly, 9e can decrease the phosphorylation of mTOR and of its downstream key proteins, S6 and P70S6K1, indicating that 9e can effectively inhibit the mTOR signaling pathway. Thus, it may have the potential to become a new mTOR inhibitor against various cancers. PMID:27150260

  19. 3-PHENYLQUINOLINYLCHALCONE DERIVATIVES: PHARMACOPHORE MODELLING, 3D-QSAR ANALYSIS AND DOCKING STUDIES AS ANTI-CANCER AGENTS

    OpenAIRE

    2014-01-01

    Certain 3-Phenylquinolinylchalcone derivatives were evaluated for their anti-proliferative activities and found to exhibit anti-cancer and anti-inflammatory activities. 3D-QSAR and molecular docking approaches were performed on 3-Phenylquinolinylchalcone derivatives to understand their structural requisites and binding mode of the best fitted ligand for cancer inhibitory activity. Among them, (E)-3-(3-(4-methoxyphenyl)quinolin-2-yl)-1-phenylprop-2-en-1-one (6a) was the most active compound ag...

  20. Preclinical Predictors of Anticancer Drug Efficacy: Critical Assessment with Emphasis on Whether Nanomolar Potency Should Be Required of Candidate Agents

    OpenAIRE

    Wong, C. C.; Cheng, Ka-Wing; Rigas, Basil

    2012-01-01

    In the current paradigm of anticancer drug development, candidate compounds are evaluated by testing their in vitro potency against molecular targets relevant to carcinogenesis, their effect on cultured cancer cells, and their ability to inhibit cancer growth in animal models. We discuss the key assumptions inherent in these approaches. In recent years, great emphasis has been placed on selecting for development compounds with nanomolar in vitro potency, expecting that they will be efficaciou...

  1. Discovery of novel heteroarylmethylcarbamodithioates as potent anticancer agents: Synthesis, structure-activity relationship analysis and biological evaluation.

    Science.gov (United States)

    Li, Ying-Bo; Yan, Xu; Li, Ri-Dong; Liu, Peng; Sun, Shao-Qian; Wang, Xin; Cui, Jing-Rong; Zhou, De-Min; Ge, Ze-Mei; Li, Run-Tao

    2016-04-13

    A series of new analogs based on the structure of lead compound 10 were designed, synthesized and evaluated for their in vitro anti-cancer activities against four selected human cancer cell lines (HL-60, Bel-7402, SK-BR-3 and MDA-MB-468). Several synthesized compounds exhibited improved anti-cancer activities comparing with lead compound 10. Among them, 1,3,4-oxadiazole analogs 17o showed highest bioactivity with IC50 values of 1.23, 0.58 and 4.29 μM against Bel-7402, SK-BR-3 and MDA-MB-468 cells, respectively. It is noteworthy that 17o has potent anti-proliferation activity toward a panel of cancer cells with relatively less cytotoxicity to nonmalignant cells. The further mechanistic study showed that it induced apoptosis and cell cycle arrest through disrupting spindle assembly in mitotic progression, indicating these synthesized dithiocarbamates represented a novel series of anti-cancer compounds targeting mitosis. PMID:26900655

  2. MEDICINAL PLANTS WITH POTENTIAL ANTICANCER ACTIVITIES: A REVIEW

    Directory of Open Access Journals (Sweden)

    Narah Merina

    2012-06-01

    Full Text Available Plants have been the beacon of therapeutic sources for curing diseases from times immemorial. Medicinal plants with their isolated lead molecules are also used as an alternative medicine for treating neoplastic cells. Neoplastic cells are the anomalous proliferation of cells in the body which cause cancer. Diverse efficient compounds derived from natural products have been isolated as anticancer agents. These chemical compounds are formulated with a view to create effective drugs against cancer. Some of the lead molecules isolated from different medicinal plants are already in use to treat cancer and chemotherapeutic side effects. These potential and successful anticancer molecules include Vincristine, Vinblastin, Taxol, Camptothecin and Podophyllotoxin. This paper deals with the selective medicinal plants having anticancer properties which could be further designed to produce cancer curing drugs.

  3. Anticancer Effect of Rutin Isolated from the Methanolic Extract of Triticum aestivum Straw in Mice

    Directory of Open Access Journals (Sweden)

    Savita Dixit

    2014-10-01

    Full Text Available Rutin is the bioactive flavanoid isolated from the straw part of Triticum aestivum and possess various pharmacological applications. The aim of this study is to evaluate the chemopreventive potential of rutin in an experimental skin carcinogenesis mice model system. Skin tumor was induced by topical application of 7,12-dimethyl benz(a anthracene (DMBA and promoted by croton oil in Swiss albino mice. To assess the chemopreventive potential of rutin, it was orally administered at a concentration of (200 mg/kg and 400 mg/kg body weight continued three times weekly for 16th weeks. The development of skin carcinogenesis was assessed by histopathological analysis. Reductions in tumor size and cumulative number of papillomas were seen due to rutin treatment. Average latent period was significantly increased as compared to carcinogen treated control. Rutin produced significant decrease in the activity of serum enzyme serum glutamate oxalate transaminase (SGOT, serum glutamate pyruvate transaminase (SGPT, alkaline phosphatase (ALP and bilirubin when compared with the control. They significantly increased the levels of enzyme involved in oxidative stress glutathione (GSH, superoxide dismutase (SOD and catalase. The elevated level of lipid peroxidase in the control group was significantly inhibited by rutin administration. The results from the present study suggest the chemopreventive effect of rutin in DMBA and croton oil induced skin carcinogenesis in swiss albino mice and one of the probable reasons would be its antioxidant potential.

  4. Antroquinonol D, isolated from Antrodia camphorata, with DNA demethylation and anticancer potential.

    Science.gov (United States)

    Wang, Sheng-Chao; Lee, Tzong-Huei; Hsu, Chun-Hua; Chang, Yu-Jia; Chang, Man-Shan; Wang, Yi-Ching; Ho, Yuan-Soon; Wen, Wu-Che; Lin, Ruo-Kai

    2014-06-18

    DNA methyltransferase 1 (DNMT1) catalyzes DNA methylation and is overexpressed in various human diseases, including cancer. A rational approach to preventing tumorigenesis involves the use of pharmacologic inhibitors of DNA methylation; these inhibitors should reactivate tumor suppressor genes (TSGs) in tumor cells and restore tumor suppressor pathways. Antroquinonol D (3-demethoxyl antroquinonol), a new DNMT1 inhibitor, was isolated from Antrodia camphorata and identified using nuclear magnetic resonance. Antroquinonol D inhibited the growth of MCF7, T47D, and MDA-MB-231 breast cancer cells without harming normal MCF10A and IMR-90 cells. The SRB assay showed that the 50% growth inhibition (GI50) in MCF7, T47D, and MDA-MB-231 breast cancer cells following treatment with antroquinonol D was 8.01, 3.57, and 25.08 μM, respectively. d-Antroquinonol also inhibited the migratory ability of MDA-MB-231 breast cancer cells in wound healing and Transwell assays. In addition, antroquinonol D inhibited DNMT1 activity, as assessed by the DNMT1 methyltransferase activity assay. As the cofactor SAM level increased, the inhibitory effects of d-antroquinonol on DNMT1 gradually decreased. An enzyme activity assay and molecular modeling revealed that antroquinonol D is bound to the catalytic domain of DNMT1 and competes for the same binding pocket in the DNMT1 enzyme as the cofactor SAM, but does not compete for the binding pocket in the DNMT3B enzyme. An Illumina Methylation 450 K array-based assay and real-time PCR assay revealed that antroquinonol D decreased the methylation status and reactivated the expression of multiple TSGs in MDA-MB-231 breast cancer cells. In conclusion, we showed that antroquinonol D induces DNA demethylation and the recovery of multiple tumor suppressor genes, while inhibiting breast cancer growth and migration potential. PMID:24784321

  5. Development of a "green process" for the isolation of natural functional extracts with anti-cancer activity - Application of high-pressure technology

    OpenAIRE

    Rodrigues, Liliana Andreia Amaro

    2014-01-01

    Dissertação para obtenção do Grau de Mestre em Engenharia Química e Bioquímica The knowledge of the healing power of some species of plants is ancient. Nowadays, the preference for natural products has increased, and with it, the interest in recover and isolate bioactive phytochemicals with potential health benefits. The main goal of this thesis was to isolate anticancer bioactive compounds, namely terpenes and fatty acids, from Portuguese Lavandula (L. angustifolia and L. stoechas) ...

  6. MEDICINAL PLANTS WITH POTENTIAL ANTICANCER ACTIVITIES: A REVIEW

    OpenAIRE

    Narah Merina; Kalita Jogen Chandra; Kotoky Jibon

    2012-01-01

    Plants have been the beacon of therapeutic sources for curing diseases from times immemorial. Medicinal plants with their isolated lead molecules are also used as an alternative medicine for treating neoplastic cells. Neoplastic cells are the anomalous proliferation of cells in the body which cause cancer. Diverse efficient compounds derived from natural products have been isolated as anticancer agents. These chemical compounds are formulated with a view to create effective drugs against can...

  7. Isolation of Candida albicans and their sensitivity to antifungal agents.

    Science.gov (United States)

    Tsai, S S; Liu, C I; Chang, C F; Tsai, Y H

    1982-02-01

    During 1978 and 1979 outbreaks of candidiasis were encountered in about 500,000 broiler chickens on 30 farms, 30,000 guinea fowl on 4 farms, 500 geese on 1 farm, and 10 penguins in a zoo. This represents the first report of avian candidiasis in Taiwan. Diagnoses were based on typical gross and microscopic pathology consistent isolation of Candida albicans from crop and esophageal lesions, virulence of isolates in rabbits, identification of the isolates as C. albicans serotype A by chlamydospore and germ tube formation, fermentation tests, and agglutination by specific antisera, and the lack of any sign of fowl pox or trichomoniasis. The upsurge of candidiasis is attributed to the modernization stressors which interact deleteriously with opportunistic pathogens. In vitro sensitivity testing recorded the following order of effectiveness against 20 isolates: nystatin greater than gentian violet greater than copper sulfate = propionic acid = p-hydroxy benzoic acid greater than calcium propionate = propylene glycol. PMID:7042231

  8. Prevalence of dermatophytes and other fungal agents isolated from clinical samples

    OpenAIRE

    Kannan P.; Janaki C; Selvi G

    2006-01-01

    The common cause of skin infections are dermatophytes and opportunistic fungi. Aim of this study was to isolate and identify the fungal agents from clinical samples from patients with different mycoses. Clinical samples from 165 patients were subjected to potassium hydroxide (KOH) examination and culture isolation; causative agents were identified macroscopically and microscopically. All the 165 specimens were KOH positive and 110/165 (66.7%) samples were culture positive. Of these, hi...

  9. In Vitro Activities of 15 Antimicrobial Agents against Clinical Isolates of South African Enterococci

    OpenAIRE

    Struwig, M. C.; Botha, P. L.; Chalkley, L. J.

    1998-01-01

    The activities of a panel of currently available antibiotics and the investigational agents LY 333328, linezolid, CL 331,002, CL 329,998, moxifloxacin (BAY 12-8039), trovafloxacin, and quinupristin-dalfopristin against 274 clinical isolates of enterococci were determined. No vancomycin resistance or β-lactamase production was observed. Except for 12 isolates (all non-Enterococcus faecalis) showing reduced susceptibility to quinupristin-dalfopristin (MIC, ≥4 μg/ml), the new agents exhibited pr...

  10. Benzene-Poly-Carboxylic Acid Complex, a Novel Anti-Cancer Agent Induces Apoptosis in Human Breast Cancer Cells

    OpenAIRE

    Fares, Fuad; Azzam, Naiel; Fares, Basem; Larsen, Stig; Lindkaer-Jensen, Steen

    2014-01-01

    Some cases of breast cancer are composed of clones of hormonal-independent growing cells, which do not respond to therapy. In the present study, the effect of Benzene-Poly-Carboxylic Acid Complex (BP-C1) on growth of human breast-cancer cells was tested. BP-C1 is a novel anti-cancer complex of benzene-poly-carboxylic acids with a very low concentration of cis-diammineplatinum (II) dichloride. Human breast cancer cells, MCF-7 and T47D, were used. Cell viability was detected by XTT assay and ap...

  11. Trends in the resistance to antimicrobial agents of Streptococcus suis isolates from Denmark and Sweden.

    Science.gov (United States)

    Aarestrup, F M; Rasmussen, S R; Artursson, K; Jensen, N E

    1998-08-28

    This study was conducted to determine the MIC values of historical and contemporary Streptoccocus suis (serotypes 2 and 7) from Denmark and S. suis (serotype 2) from Sweden. A total of 52 isolates originating from 1967 through 1981 and 156 isolates from 1992 through 1997 in Denmark and 13 isolates from Sweden were examined for their MICs against 20 different antimicrobial agents. Most antimicrobials were active against most isolates. A frequent occurrence of resistance to sulphamethoxazole was observed, with most resistance among historic isolates of serotype 7 and least resistance among isolates from Sweden. A large number of the isolates was resistant to macrolides. However, all historic serotype 2 isolates from Denmark were susceptible, whereas 20.4% of the contemporary isolates were resistant. Among serotype 7 isolates 23.3% of the historic isolates were resistant to macrolides, whereas resistance was found in 44.8% of the contemporary isolates. All isolates from Sweden were susceptible to macrolides. Time-associated frequency of resistance to tetracycline was also found. Only a single historic isolate of serotype 2 was resistant to tetracycline, whereas 43.9% of the contemporary serotype 2 isolates and 15.5% of the contemporary serotype 7 isolates were resistant. Only one (7.7%) of the isolates from Sweden was resistant. The differences in resistance between historic and contemporary isolates from Denmark were statistically significant. This study demonstrated a significant serotype-associated difference in the susceptibility to macrolides and tetracycline and demonstrated that an increase in resistance among S. suis isolates has taken place during the last 15 years to the two most commonly used antimicrobial agents (tylosin and tetracycline) in pig production in Denmark. PMID:9810623

  12. Rational design, synthesis, and biological evaluation of third generation α-noscapine analogues as potent tubulin binding anti-cancer agents.

    Directory of Open Access Journals (Sweden)

    Naresh Kumar Manchukonda

    Full Text Available Systematic screening based on structural similarity of drugs such as colchicine and podophyllotoxin led to identification of noscapine, a microtubule-targeted agent that attenuates the dynamic instability of microtubules without affecting the total polymer mass of microtubules. We report a new generation of noscapine derivatives as potential tubulin binding anti-cancer agents. Molecular modeling experiments of these derivatives 5a, 6a-j yielded better docking score (-7.252 to -5.402 kCal/mol than the parent compound, noscapine (-5.505 kCal/mol and its existing derivatives (-5.563 to -6.412 kCal/mol. Free energy (ΔG bind calculations based on the linear interaction energy (LIE empirical equation utilizing Surface Generalized Born (SGB continuum solvent model predicted the tubulin-binding affinities for the derivatives 5a, 6a-j (ranging from -4.923 to -6.189 kCal/mol. Compound 6f showed highest binding affinity to tubulin (-6.189 kCal/mol. The experimental evaluation of these compounds corroborated with theoretical studies. N-(3-brormobenzyl noscapine (6f binds tubulin with highest binding affinity (KD, 38 ± 4.0 µM, which is ~ 4.0 times higher than that of the parent compound, noscapine (KD, 144 ± 1.0 µM and is also more potent than that of the first generation clinical candidate EM011, 9-bromonoscapine (KD, 54 ± 9.1 µM. All these compounds exhibited substantial cytotoxicity toward cancer cells, with IC50 values ranging from 6.7 µM to 72.9 µM; compound 6f showed prominent anti-cancer efficacy with IC50 values ranging from 6.7 µM to 26.9 µM in cancer cells of different tissues of origin. These compounds perturbed DNA synthesis, delayed the cell cycle progression at G2/M phase, and induced apoptotic cell death in cancer cells. Collectively, the study reported here identified potent, third generation noscapinoids as new anti-cancer agents.

  13. From COX-2 inhibitor nimesulide to potent anti-cancer agent: synthesis, in vitro, in vivo and pharmacokinetic evaluation.

    Science.gov (United States)

    Zhong, Bo; Cai, Xiaohan; Chennamaneni, Snigdha; Yi, Xin; Liu, Lili; Pink, John J; Dowlati, Afshin; Xu, Yan; Zhou, Aimin; Su, Bin

    2012-01-01

    Cyclooxygenase-2 (COX-2) inhibitor nimesulide inhibits the proliferation of various types of cancer cells mainly via COX-2 independent mechanisms, which makes it a good lead compound for anti-cancer drug development. In the presented study, a series of new nimesulide analogs were synthesized based on the structure-function analysis generated previously. Some of them displayed very potent anti-cancer activity with IC(50)s around 100 nM-200 nM to inhibit SKBR-3 breast cancer cell growth. CSUOH0901 (NSC751382) from the compound library also inhibits the growth of the 60 cancer cell lines used at National Cancer Institute Developmental therapeutics Program (NCIDTP) with IC(50)s around 100 nM-500 nM. Intraperitoneal injection with a dosage of 5  mg/kg/d of CSUOH0901 to nude mice suppresses HT29 colorectal xenograft growth. Pharmacokinetic studies demonstrate the good bioavailability of the compound. PMID:22119125

  14. Specific Design of Titanium(IV) Phenolato Chelates Yields Stable and Accessible, Effective and Selective Anticancer Agents.

    Science.gov (United States)

    Meker, Sigalit; Braitbard, Ori; Hall, Matthew D; Hochman, Jacob; Tshuva, Edit Y

    2016-07-11

    Octahedral titanium(IV) complexes of phenolato hexadentate ligands were developed and showed very high stability for days in water solutions. In vitro cytotoxicity studies showed that, whereas tetrakis(phenolato) systems are generally of low activity presumably due to inaccessibility, smaller bis(phenolato)bis(alkoxo) complexes feature high anticancer activity and accessibility even without formulations, also toward a cisplatin-resistant cell line. An all-aliphatic control complex was unstable and inactive. A leading phenolato complex also revealed: 1) high durability in fully aqueous solutions; accordingly, negligible loss of activity after preincubation for three days in medium or in serum; 2) maximal cellular accumulation and induction of apoptosis following 24-48 h of administration; 3) reduced impact on noncancerous fibroblast cells; 4) in vivo efficacy toward lymphoma cells in murine model; 5) high activity in NCI-60 panel, with average GI50 of 4.6±2 μm. This newly developed family of Ti(IV) complexes is thus of great potential for anticancer therapy. PMID:27320784

  15. Synthesis and anticancer activity of some novel indolo[3,2-b]andrographolide derivatives as apoptosis-inducing agents.

    Science.gov (United States)

    Song, Yaping; Xin, Zhengyuan; Wan, Yumeng; Li, Jiabin; Ye, Boping; Xue, Xiaowen

    2015-01-27

    A series of novel indolo[3,2-b]andrographolide derivatives were designed, synthesized and screened in vitro against three human cancer cell lines MCF7 (human breast cancer), HCT116 (human colon cancer), and DU145 (human prostate cancer). Fourteen compounds 6b, 6e, 6i, 6j, 6l, 6m, 6n, 12a, 12b, 13a, 13b, 15a, 17a, and 17b exhibited better anti-cancer activities than andrographolide for all three human cancer lines, with compound 6l displaying best activity with IC50 values of 1.85, 1.22 and 1.24 μM against MCF7, HCT116 and DU145 respectively. Preliminary anti-cancer mechanistic investigation was performed in terms of the cell cycle arrest and cell apoptosis assays of compound 6l against HCT116 using flow cytometry, and the results suggested that compound 6l inhibited tumor proliferation through inducing early and late cellular apoptosis in a concentration-dependent manner and causing cell cycle arrest in the S-phase. PMID:25506809

  16. Identification of anticancer agents based on the thieno[2,3-b]pyridine and 1H-pyrazole molecular scaffolds.

    Science.gov (United States)

    Eurtivong, Chatchakorn; Reynisdóttir, Inga; Kuczma, Stephanie; Furkert, Daniel P; Brimble, Margaret A; Reynisson, Jóhannes

    2016-08-15

    Structural similarity search of commercially available analogues of thieno[2,3-b]pyridine and 1H-pyrazole derivatives, known anticancer agents, resulted in 717 hits. These were docked into the phosphoinositide specific-phospholipase C (PLC) binding pocket, the putative target of the compounds, to further focus the selection. Thirteen derivatives of the thieno[2,3-b]pyridines were identified and tested against the NCI60 panel of human tumour cell lines. The most active derivative 1 was most potent against the MDA-MB-435 melanoma cell line with GI50 at 30nM. Also, it was found that a piperidine moiety is tolerated on the thieno[2,3-b]pyridine scaffold with GI50=296nM (MDA-MB-435) for derivative 10 considerably expanding the structure activity relationship for the series. For the 1H-pyrazoles four derivatives were identified using the in silico approach and additionally ten were synthesised with various substituents on the phenyl moiety to extend the structural activity relationship but only modest anticancer activity was found. PMID:27288184

  17. Localized sequence-specific release of a chemopreventive agent and an anticancer drug in a time-controllable manner to enhance therapeutic efficacy.

    Science.gov (United States)

    Pan, Wen-Yu; Lin, Kun-Ju; Huang, Chieh-Cheng; Chiang, Wei-Lun; Lin, Yu-Jung; Lin, Wei-Chih; Chuang, Er-Yuan; Chang, Yen; Sung, Hsing-Wen

    2016-09-01

    Combination chemotherapy with multiple drugs commonly requires several injections on various schedules, and the probability that the drug molecules reach the diseased tissues at the proper time and effective therapeutic concentrations is very low. This work elucidates an injectable co-delivery system that is based on cationic liposomes that are adsorbed on anionic hollow microspheres (Lipos-HMs) via electrostatic interaction, from which the localized sequence-specific release of a chemopreventive agent (1,25(OH)2D3) and an anticancer drug (doxorubicin; DOX) can be thermally driven in a time-controllable manner by an externally applied high-frequency magnetic field (HFMF). Lipos-HMs can greatly promote the accumulation of reactive oxygen species (ROS) in tumor cells by reducing their cytoplasmic expression of an antioxidant enzyme (superoxide dismutase) by 1,25(OH)2D3, increasing the susceptibility of cancer cells to the cytotoxic action of DOX. In nude mice that bear xenograft tumors, treatment with Lipos-HMs under exposure to HFMF effectively inhibits tumor growth and is the most effective therapeutic intervention among all the investigated. These empirical results demonstrate that the synergistic anticancer effects of sequential release of 1,25(OH)2D3 and DOX from the Lipos-HMs may have potential for maximizing DOX cytotoxicity, supporting more effective cancer treatment. PMID:27294541

  18. Effects of intra-arterial chemotherapy with a new lipophilic anticancer agent, estradiol-chlorambucil (KM2210), dissolved in lipiodol on experimental liver tumor in rats

    International Nuclear Information System (INIS)

    Anticancer effects and biodistribution of a new lipophilic anticancer agent, estradiol-chlorambucil (KM2210), dissolved in lipiodol (LPD) were investigated as an intra-arterial chemotherapy (IAC) on Walker 256 carcinosarcoma grown in the liver of 136 Wistar rats. All rats treated with KM2210 (10 mg)-LPD survived for 90 days after administration, whereas none of the rats with LPD alone were alive for more than 19 days. Histological examination revealed that there was no viable tumor cell in the encapsulated necrotic tumor at 21 days after administration. There was no significant liver dysfunction or leukopenia due to KM2210. The biodistribution study using [14C, 3H]KM2210-LPD solution showed that KM2210 accumulated selectively in tumor and that the tumor-to-normal-liver and tumor-to-blood ratios were 10 and 1,000, respectively, at 21 days after administration. These results suggest that KM2210 has potential clinical application in the treatment of human liver cancer

  19. Evaluation of a curcumin analog as an anti-cancer agent inducing ER stress-mediated apoptosis in non-small cell lung cancer cells

    International Nuclear Information System (INIS)

    Recent advances have highlighted the importance of the endoplasmic reticulum (ER) in cell death processes. Pharmacological interventions that effectively enhance tumor cell death through activating ER stress have attracted a great deal of attention for anti-cancer therapy. A bio-evaluation on 113 curcumin analogs against four cancer cell lines was performed through MTT assay. Furthermore, real time cell assay and flow cytometer were used to evaluate the apoptotic induction of (1E,4E)-1,5-bis(5-bromo-2-ethoxyphenyl)penta-1,4-dien-3-one (B82). Western blot, RT-qPCR, and siRNA were then utilized to confirm whether B82-induced apoptosis is mediated through activating ER stress pathway. Finally, the in vivo anti-tumor effect of B82 was evaluated. B82 exhibited strong anti-tumor activity in non-small cell lung cancer (NSCLC) H460 cells. Treatment with B82 significantly induced apoptosis in H460 cells in vitro and inhibited H460 tumor growth in vivo. Further studies demonstrated that the B82-induced apoptosis is mediated by activating ER stress both in vitro and in vivo. A new monocarbonyl analog of curcumin, B82, exhibited anti-tumor effects on H460 cells via an ER stress-mediated mechanism. B82 could be further explored as a potential anticancer agent for the treatment of NSCLC

  20. Synthesis, biological evaluation, drug-likeness, and in silico screening of novel benzylidene-hydrazone analogues as small molecule anticancer agents.

    Science.gov (United States)

    Alam, Mohammad Sayed; Lee, Dong-Ung

    2016-02-01

    A series of fifteen benzylidene-hydrazone analogues (3a-o), including eight new compounds, were synthesized and evaluated for their cytotoxic activities in four human cancer cell lines and for their antioxidant activities using DPPH. Of the tested compounds 3e, which possesses two methoxy substituents in its benzylidene phenyl ring, was found to be potently cytotoxic to all cancer cell lines tested with IC50 values of 0.12 (lung), 0.024 (ovarian), 0.097 (melanoma), and 0.05 μM (colon), and these IC50 values were comparable to those of the doxorubicin standard (IC50 = 0.021, 0.074, 0.001, and 0.872 μM, respectively). DPPH assay showed compounds 3f, 3i, and 3g had IC50 values of 0.60, 0.99, and 1.30 μM, respectively, which were comparable to that of ascorbic acid (IC50 = 0.87 μM). Computational parameters such as, drug-likeness, ADME properties, toxicity effects, and drug scores were evaluated, and none of the fifteen compounds violated Lipinski's rule of five or Veber's rule, and thus they demonstrated good drug-likeness properties. In addition, all fifteen compounds had a higher drug score than the doxorubicin and BIBR1532. In silico screening was also conducted by docking of the active compounds on the active site of telomerase reverse transcriptase catalytic subunit, an important therapeutic target of anticancer agents, to determine the probable binding properties. The total binding energies of docked compounds are correlated well with cytotoxic potencies (pIC50) against lung, ovarian, melanoma, and colon cancer cell lines indicating that the benzylidene-hydrazones could use for the development of new anticancer agents as a telomerase inhibitor. PMID:26694484

  1. Essential oils from Egyptian aromatic plants as antioxidant and novel anticancer agents in human cancer cell lines

    Directory of Open Access Journals (Sweden)

    Ramadan, M. M.

    2015-06-01

    Full Text Available Inhibitors of tumor growth using extracts from aromatic plants are rapidly emerging as important new drug candidates for cancer therapy. The cytotoxicity and in vitro anticancer evaluation of the essential oils from thyme, juniper and clove has been assessed against five different human cancer cell lines (liver HepG2, breast MCF-7, prostate PC3, colon HCT116 and lung A549. A GC/MS analysis revealed that α-pinene, thymol and eugenol are the major components of Egyptian juniper, thyme and clove oils with concentrations of 31.19%, 79.15% and 82.71%, respectively. Strong antioxidant profiles of all the oils are revealed in vitro by DPPH and β-carotene bleaching assays. The results showed that clove oil was similarly potent to the reference drug, doxorubicin in prostate, colon and lung cell lines. Thyme oil was more effective than the doxorubicin in breast and lung cell lines while juniper oil was more effective than the doxorubicin in all the tested cancer cell lines except prostate cancer. In conclusion, the essential oils from Egyptian aromatic plants can be used as good candidates for novel therapeutic strategies for cancer as they possess significant anticancer activity.Los inhibidores de crecimiento de tumores usando extractos de plantas aromáticas están emergiendo con rapidez como nuevos e importantes medicamentos para el tratamiento del cáncer. La citotoxicidad y la acción anticancerígena in vitro de aceites esenciales de tomillo, enebro y clavo han sido evaluadas en cinco líneas celulares de cáncer humano (hígado HepG2, mama MCF-7, próstata PC3, colon HCT116 y pulmón A549. Los análisis de GC/MS mostraron que α-pineno, timol y eugenol son los principales componentes de los aceites egipcios de enebro, tomillo y clavo, con concentraciones de 31,19%, 79,15% y 82,71%, respectivamente. Se demuestra, mediante ensayos in vitro de blanqueo de DPPH y β-caroteno, el enérgico perfil antioxidante de todos los aceites. Los resultados

  2. Characterization of Novel Trichoderma asperellum Isolates to Select Effective Biocontrol Agents Against Tomato Fusarium Wilt.

    Science.gov (United States)

    El Komy, Mahmoud H; Saleh, Amgad A; Eranthodi, Anas; Molan, Younes Y

    2015-03-01

    The use of novel isolates of Trichoderma with efficient antagonistic capacity against Fusarium oxysporum f. sp. lycopersici (FOL) is a promising alternative strategy to pesticides for tomato wilt management. We evaluated the antagonistic activity of 30 isolates of T. asperellum against 4 different isolates of FOL. The production of extracellular cell wall degrading enzymes of the antagonistic isolates was also measured. The random amplified polymorphic DNA (RAPD) method was applied to assess the genetic variability among the T. asperellum isolates. All of the T. asperellum isolates significantly reduced the mycelial growth of FOL isolates but the amount of growth reduction varied significantly as well. There was a correlation between the antagonistic capacity of T. asperellum isolates towards FOL and their lytic enzyme production. Isolates showing high levels of chitinase and β-1,3-glucanase activities strongly inhibited the growth of FOL isolates. RAPD analysis showed a high level of genetic variation among T. asperellum isolates. The UPGMA dendrogram revealed that T. asperellum isolates could not be grouped by their anta- gonistic behavior or lytic enzymes production. Six isolates of T. asperellum were highly antagonistic towards FOL and potentially could be used in commercial agriculture to control tomato wilt. Our results are consistent with the conclusion that understanding the genetic variation within Trichoderma isolates and their biochemical capabilities are required for the selection of effective indigenous fungal strains for the use as biocontrol agents. PMID:25774110

  3. Marine-Sourced Anti-Cancer and Cancer Pain Control Agents in Clinical and Late Preclinical Development †

    OpenAIRE

    Newman, David J; Cragg, Gordon M.

    2014-01-01

    The marine habitat has produced a significant number of very potent marine-derived agents that have the potential to inhibit the growth of human tumor cells in vitro and, in a number of cases, in both in vivo murine models and in humans. Although many agents have entered clinical trials in cancer, to date, only Cytarabine, Yondelis® (ET743), Eribulin (a synthetic derivative based on the structure of halichondrin B), and the dolastatin 10 derivative, monomethylauristatin E (MMAE or vedotin) ...

  4. A translational study “case report” on the small molecule “energy blocker” 3-bromopyruvate (3BP) as a potent anticancer agent: from bench side to bedside

    NARCIS (Netherlands)

    Ko, Y.H.; Verhoeven, H.A.; Lee, M.J.; Corbin, D.J.; Vogl, T.J.; Pedersen, P.L.

    2012-01-01

    The small alkylating molecule, 3-bromopyruvate (3BP), is a potent and specific anticancer agent. 3BP is different in its action from most currently available chemo-drugs. Thus, 3BP targets cancer cells’ energy metabolism, both its high glycolysis (“Warburg Effect”) and mitochondrial oxidative phosph

  5. Marine-Sourced Anti-Cancer and Cancer Pain Control Agents in Clinical and Late Preclinical Development

    Directory of Open Access Journals (Sweden)

    David J. Newman

    2014-01-01

    Full Text Available The marine habitat has produced a significant number of very potent marine-derived agents that have the potential to inhibit the growth of human tumor cells in vitro and, in a number of cases, in both in vivo murine models and in humans. Although many agents have entered clinical trials in cancer, to date, only Cytarabine, Yondelis® (ET743, Eribulin (a synthetic derivative based on the structure of halichondrin B, and the dolastatin 10 derivative, monomethylauristatin E (MMAE or vedotin as a warhead, have been approved for use in humans (Adcetris®. In this review, we show the compounds derived from marine sources that are currently in clinical trials against cancer. We have included brief discussions of the approved agents, where they are in trials to extend their initial approved activity (a common practice once an agent is approved, and have also included an extensive discussion of the use of auristatin derivatives as warheads, plus an area that has rarely been covered, the use of marine-derived agents to ameliorate the pain from cancers in humans, and to act as an adjuvant in immunological therapies.

  6. Benzene-Poly-Carboxylic Acid Complex, a Novel Anti-Cancer Agent Induces Apoptosis in Human Breast Cancer Cells

    Science.gov (United States)

    Fares, Fuad; Azzam, Naiel; Fares, Basem; Larsen, Stig; Lindkaer-Jensen, Steen

    2014-01-01

    Some cases of breast cancer are composed of clones of hormonal-independent growing cells, which do not respond to therapy. In the present study, the effect of Benzene-Poly-Carboxylic Acid Complex (BP-C1) on growth of human breast-cancer cells was tested. BP-C1 is a novel anti-cancer complex of benzene-poly-carboxylic acids with a very low concentration of cis-diammineplatinum (II) dichloride. Human breast cancer cells, MCF-7 and T47D, were used. Cell viability was detected by XTT assay and apoptosis was detected by Flow Cytometry and by annexin V/FITC/PI assay. Caspases were detected by western blot analysis and gene expression was measured by using the Applied Biosystems® TaqMan® Array Plates. The results showed that exposure of the cells to BP-C1 for 48 h, significantly (P<0.001) reduced cell viability, induced apoptosis and activated caspase 8 and caspace 9. Moreover, gene expression experiments indicated that BP-C1 increased the expression of pro-apoptotic genes (CASP8AP1, TNFRSF21, NFkB2, FADD, BCL10 and CASP8) and lowered the level of mRNA transcripts of inhibitory apoptotic genes (BCL2L11, BCL2L2 and XIAP. These findings may lead to the development of new therapeutic strategies for treatment of human cancer using BP-C1 analog. PMID:24523856

  7. Synthesis and Cytotoxicity Evaluation of 13-n-Alkyl Berberine and Palmatine Analogues as Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2012-09-01

    Full Text Available By introducing long carbon-chain alkyl groups at the C-13 position of berberine and palmatine, 13-n-hexyl/13-n-octyl berberine and palmatine chloride analogues 4ad were synthesized and examined by MTT assays for cytotoxic activity in seven human cancer cell lines (7701QGY, SMMC7721, HepG2, CEM, CEM/VCR, KIII, Lewis, yielding IC50 values of 0.02 ± 0.01–13.58 ± 2.84 μM. 13-n-Octyl palmatine (compound 4d gave the most potent inhibitor activity, with an IC50 of 0.02 ± 0.01 μM for SMMC7721. In all cases, the 13-n-alkyl berberine and palmatine analogues 4ad were more cytotoxic than berberine and palmatine. In addition, compounds 4ad also exhibited more potent cytotoxicity than berberine and palmatine in mice with S180 sarcoma xenografted in vivo. The primary screening results indicated that the 13-n-hexyl/13-n-octyl berberine and palmatine analogues might be valuable source for new potent anticancer drug candidates.

  8. shRNA Depletion of cIAP1 Sensitizes Human Ovarian Cancer Cells to Anticancer Agent-Induced Apoptosis.

    Science.gov (United States)

    Jin, Hong; Dong, You-Yuan; Zhang, Hong; Cui, Ying; Xie, Kai; Lou, Ge

    2014-01-01

    Emerging evidence suggests a potential role of cellular inhibitor of apoptosis protein 1 (cIAP1) in the development of human ovarian cancer. However, its function in the progression of ovarian cancer has not been clearly determined. Our study aimed to investigate the effect of cIAP1 gene depletion on the chemosensitivity of ovarian cancer cells. We developed a novel short hairpin RNA (shRNA) plasmid specifically targeting cIAP1. Cell proliferation, invasion, and apoptosis of the shRNA-transfected cells were evaluated using MTT, Transwell chamber, and flow cytometric assays, respectively. The concentration of MMP-9 in the supernatant was detected by ELISA. Targeted depletion of cIAP1 by shRNA significantly reduced expression levels of cIAP1 mRNA and protein, leading to inhibition of cell proliferation and invasion capability in SKOV3 cells. At the same time, cIAP1 downregulation decreased the secretion of MMP-9. shRNA depletion of cIAP1 enhanced chemosensitivity of ovarian cancer cells to Taxol and carboplatin-induced apoptosis. cIAP1 is associated with tumor progression in human ovarian cancer. Therefore, cIAP1 might be a potential target for therapeutic anticancer drugs. PMID:26168135

  9. 3-D QSAR CoMFA study of nitrogen mustards possessing new chemical entities as possible anticancer agents

    Directory of Open Access Journals (Sweden)

    Anand R

    2006-01-01

    Full Text Available This present work is an investigation of anticancer activities of the nitrogen mustards possessing quinazolinone, benzimidazole, benzoxazole, and benzothiazole nuclei by the three-dimensional Quantitative Structure Activity paradigm, Comparative Molecular Field Analysis. A total of 39 compounds were modelled in SYBYL 6.7 (Tripos, USA. The molecules were aligned by root-mean-square fit of atoms and field fit of the steric and electrostatic molecular fields and the resulting databases analysed by partial least squares analysis with cross-validation, leave-one-out and no validation to extract the optimum number of components. The analysis was then repeated with bootstrapping to give the final Quantitative Structure Activity Relationship models. Eight compounds, which were kept separately as test set, were used to test the predictive ability of the Comparative Molecular Field Analysis models. Out of the two models generated, one was found to be useful. The predicted activities of the test set were in good agreement with experimentally determined values.

  10. The disulfide compound α-lipoic acid and its derivatives: A novel class of anticancer agents targeting mitochondria.

    Science.gov (United States)

    Dörsam, Bastian; Fahrer, Jörg

    2016-02-01

    The endogenous disulfide α-lipoic acid (LA) is an essential mitochondrial co-factor. In addition, LA and its reduced counterpart dihydro lipoic acid form a potent redox couple with antioxidative functions, for which it is used as dietary supplement and therapeutic. Recently, it has gained attention due to its cytotoxic effects in cancer cells, which is the key aspect of this review. We initially recapitulate the dietary occurrence, gastrointestinal absorption and pharmacokinetics of LA, illustrating its diverse antioxidative mechanisms. We then focus on its mode of action in cancer cells, in which it triggers primarily the mitochondrial pathway of apoptosis, whereas non-transformed primary cells are hardly affected. Furthermore, LA impairs oncogenic signaling and displays anti-metastatic potential. Novel LA derivatives such as CPI-613, which target mitochondrial energy metabolism, are described and recent pre-clinical studies are presented, which demonstrate that LA and its derivatives exert antitumor activity in vivo. Finally, we highlight clinical studies currently performed with the LA analog CPI-613. In summary, LA and its derivatives are promising candidates to complement the arsenal of established anticancer drugs due to their mitochondria-targeted mode of action and non-genotoxic properties. PMID:26604131

  11. Stimuli-responsive protamine-based biodegradable nanocapsules for enhanced bioavailability and intracellular delivery of anticancer agents

    International Nuclear Information System (INIS)

    Enzyme- and pH-responsive polyelectrolyte nanocapsules having diameters in the range of 200 ± 20 nm were fabricated by means of Layer-by-Layer assembly of biopolymers, protamine, and heparin, and then loaded with anticancer drug doxorubicin. The incorporation of the FDA-approved peptide drug protamine as a wall component rendered the capsules responsive to enzyme stimuli. The stimuli-responsive drug release from these nanocapsules was evaluated, and further modulation of capsule permeability to avoid premature release was demonstrated by crosslinking the wall components. The interaction of the nanocapsules with cancer cells was studied using MCF-7 breast cancer cells. These capsules were readily internalized and disintegrated inside the cells, culminating in the release of the loaded doxorubicin and subsequent cell death as observed by confocal microscopy and MTT Assay. The bioavailability studies performed using BALB/c mice revealed that the encapsulated doxorubicin exhibited enhanced bioavailability compared to free doxorubicin. Our results indicate that this stimuli-responsive system fabricated from clinically used FDA-approved molecules and exhibiting minimal premature release has great potential for drug-delivery applications.

  12. Stimuli-responsive protamine-based biodegradable nanocapsules for enhanced bioavailability and intracellular delivery of anticancer agents

    Energy Technology Data Exchange (ETDEWEB)

    Radhakrishnan, Krishna; Thomas, Midhun B.; Pulakkat, Sreeranjini [Indian Institute of Science, Department of Materials Engineering (India); Gnanadhas, Divya P.; Chakravortty, Dipshikha [Indian Institute of Science, Department of Microbiology and Cell Biology (India); Raichur, Ashok M., E-mail: amr@materials.iisc.ernet.in [Indian Institute of Science, Department of Materials Engineering (India)

    2015-08-15

    Enzyme- and pH-responsive polyelectrolyte nanocapsules having diameters in the range of 200 ± 20 nm were fabricated by means of Layer-by-Layer assembly of biopolymers, protamine, and heparin, and then loaded with anticancer drug doxorubicin. The incorporation of the FDA-approved peptide drug protamine as a wall component rendered the capsules responsive to enzyme stimuli. The stimuli-responsive drug release from these nanocapsules was evaluated, and further modulation of capsule permeability to avoid premature release was demonstrated by crosslinking the wall components. The interaction of the nanocapsules with cancer cells was studied using MCF-7 breast cancer cells. These capsules were readily internalized and disintegrated inside the cells, culminating in the release of the loaded doxorubicin and subsequent cell death as observed by confocal microscopy and MTT Assay. The bioavailability studies performed using BALB/c mice revealed that the encapsulated doxorubicin exhibited enhanced bioavailability compared to free doxorubicin. Our results indicate that this stimuli-responsive system fabricated from clinically used FDA-approved molecules and exhibiting minimal premature release has great potential for drug-delivery applications.

  13. Response of drug resistant isolates of Schistosoma mansoni to antischistosomal agents

    Directory of Open Access Journals (Sweden)

    Kristen M. Drescher

    1993-03-01

    Full Text Available The susceptibility of four isolates of Schistosoma mansoni (BH, MAP, MPR-1 and K to four multiple doses of anti-schistosomal agents (hycanthone, niridazole, oxamniquire, and praziquantel were evaluated in infected female Swiss albino mice. These schistosomal isolates had been maintained in the laboratory without further drug pressure for 20 to 30 generations. Multiple dosage regimens were used for each drug against each isolate of S. mansoni to generate ED50 (effective dose 50% values. Results demonstrated that the K isolate is resistant to niridazole, the MPR-1 isolate to oxamniquine, and the MAP isolate to both hycanthone and oxamniquine. The BH isolate was susceptible to all drugs and was used as the reference isolate. All isolates were susceptible to praziquantel. The significance of the difference in response of the MPR-1 and MAP isolates is discussed. These results confirm the resistance of these isolates of S. mansoni of three schistosomicides and demonstrate that the resistance of these isolates are stable over long periods of time without exposure to drugs.

  14. Mode of action and resistance studies unveil new roles for tropodithietic acid as an anticancer agent and the γ-glutamyl cycle as a proton sink.

    Science.gov (United States)

    Wilson, Maxwell Z; Wang, Rurun; Gitai, Zemer; Seyedsayamdost, Mohammad R

    2016-02-01

    While we have come to appreciate the architectural complexity of microbially synthesized secondary metabolites, far less attention has been paid to linking their structural features with possible modes of action. This is certainly the case with tropodithietic acid (TDA), a broad-spectrum antibiotic generated by marine bacteria that engage in dynamic symbioses with microscopic algae. TDA promotes algal health by killing unwanted marine pathogens; however, its mode of action (MoA) and significance for the survival of an algal-bacterial miniecosystem remains unknown. Using cytological profiling, we herein determine the MoA of TDA and surprisingly find that it acts by a mechanism similar to polyether antibiotics, which are structurally highly divergent. We show that like polyether drugs, TDA collapses the proton motive force by a proton antiport mechanism, in which extracellular protons are exchanged for cytoplasmic cations. The α-carboxy-tropone substructure is ideal for this purpose as the proton can be carried on the carboxyl group, whereas the basicity of the tropylium ion facilitates cation export. Based on similarities to polyether anticancer agents we have further examined TDA's cytotoxicity and find it to exhibit potent, broad-spectrum anticancer activities. These results highlight the power of MoA-profiling technologies in repurposing old drugs for new targets. In addition, we identify an operon that confers TDA resistance to the producing marine bacteria. Bioinformatic and biochemical analyses of these genes lead to a previously unknown metabolic link between TDA/acid resistance and the γ-glutamyl cycle. The implications of this resistance mechanism in the context of the algal-bacterial symbiosis are discussed. PMID:26802120

  15. Development of an LC-MS/MS method for analysis of interconvertible Z/E isomers of the novel anticancer agent, Bp4eT.

    Science.gov (United States)

    Stariat, Ján; Kovaríková, Petra; Klimes, Jirí; Kalinowski, Danuta S; Richardson, Des R

    2010-05-01

    This study was focused on a liquid chromatography/tandem mass spectrometry (LC/MS/MS) method development for quantification of a novel potential anticancer agent, 2-benzoylpyridine 4-ethyl-3-thiosemicarbazone (Bp4eT), in aqueous media. Solid Bp4eT was found to consist predominantly of the Z isomer, while in aqueous media, both isomers coexist. Sufficient separation of both isomers was achieved on a Synergi 4u Polar RP column with a mobile phase composed of 2 mM ammonium formate, acetonitrile, and methanol (30:63:7; v/v/v). The photo diode array analysis of both isomers demonstrated different absorption spectra which hindered UV-based quantification. However, an equal and reproducible response was found for both isomers using an MS detector, which enables the determination of the total content of Bp4eT (i.e., both E- and Z- isomeric forms) by summation of the peak areas of both isomers. 2-Hydroxy-1-naphthylaldehyde 4-methyl-3-thiosemicarbazone (N4mT) was selected as the internal standard. Quantification was performed in selective reaction monitoring using the main fragments of [M+H](+) (240 m/z for Bp4eT and 229 m/z for N4mT). The method was validated over 20-600 ng/ml. This procedure was applied to a preformulation study to determine the proper vehicle for parenteral administration. It was found that Bp4eT was poorly soluble in aqueous media. However, the solubility can be effectively improved using pharmaceutical cosolvents. In fact, a 1:1 mixture of PEG 300/0.14 M saline markedly increased solubility and may be a useful drug formulation for intravenous administration. This investigation further accelerates development of novel anticancer thiosemicarbazones. The described methods will be useful for analogs currently under development and suffering the same analytical issue. PMID:20127082

  16. Molecular and Pharmacologic Properties of the Anticancer Quinolone Derivative Vosaroxin: A New Therapeutic Agent for Acute Myeloid Leukemia.

    Science.gov (United States)

    Jamieson, Gene C; Fox, Judith A; Poi, Ming; Strickland, Stephen A

    2016-09-01

    Vosaroxin is a first-in-class anticancer quinolone derivative that targets topoisomerase II and induces site-selective double-strand breaks in DNA, leading to tumor cell apoptosis. Vosaroxin has chemical and pharmacologic characteristics distinct from other topoisomerase II inhibitors due to its quinolone scaffold. The efficacy and safety of vosaroxin in combination with cytarabine were evaluated in patients with relapsed/refractory acute myeloid leukemia (AML) in a phase III, randomized, multicenter, double-blind, placebo-controlled study (VALOR). In this study, the addition of vosaroxin produced a 1.4-month improvement in median overall survival (OS; 7.5 months with vosaroxin/cytarabine vs. 6.1 months with placebo/cytarabine; hazard ratio [HR] 0.87, 95 % confidence interval [CI] 0.73-1.02; unstratified log-rank p [Formula: see text] 0.061; stratified log-rank p [Formula: see text]0.024), with the greatest OS benefit observed in patients ≥60 years of age (7.1 vs. 5.0 months; HR 0.75, 95 % CI 0.62-0.92; p [Formula: see text]0.003) and patients with early relapse (6.7 vs. 5.2 months; HR 0.77, 95 % CI 0.59-1.00; p [Formula: see text] 0.039), two AML patient groups that typically have poor prognosis. Here we review the chemical and pharmacologic properties of vosaroxin, how these properties are distinct from those of currently available topoisomerase II inhibitors, how they may contribute to the efficacy and safety profile observed in the VALOR trial, and the status of clinical development of vosaroxin for treatment of AML. PMID:27484675

  17. Susceptibility to antimicrobial agents and plasmid carrying in Aeromonas hydrophila isolated from two estuarine systems.

    Science.gov (United States)

    Montoya, R; Dominguez, M; Gonzalez, C; Mondaca, M A; Zemelman, R

    1992-01-01

    Susceptibility to various antimicrobial agents and the presence of plasmids was investigated in eleven strains of Aeromonas hydrophila isolated from samples of sea water and these strains isolated from Aulacomya ater. Transference of resistance to Escherichia coli was attempted by conjugation and transformation experiments. The strains showed multiple resistance toward beta-lactam antibiotics and susceptibility to other antimicrobial agents. Five strains harboured plasmids with molecular weights below 5.7 MD. It was not possible to relate the resistance of the strains with the presence of their plasmids. PMID:1593967

  18. The in vitro activity of 15 antimicrobial agents against bacterial isolates from dogs.

    Science.gov (United States)

    Awji, Elias Gebru; Damte, Dereje; Lee, Seung-Jin; Lee, Joong-Su; Kim, Young-Hoan; Park, Seung-Chun

    2012-08-01

    The in vitro activity of 15 antimicrobial agents against clinical isolates of Staphylococcus pseudintermedius, Staphylococcus aureus, Escherichia coli, Pasteurella spp. and Streptococcus canis from dogs was investigated. For Staphylococcus spp., the highest frequency of resistance was observed for penicillin, followed by ampicillin, tetracycline and chloramphenicol. The highest frequency of resistance in E. coli isolates was recorded for tetracycline and streptomycin. Pasteurella spp. and S. canis had the highest resistance rate for tetracycline and chloramphenicol. Most isolates showed full susceptibility to low-level resistance to colistin, florfenicol and fluoroquinolones. Further studies using larger number of isolates from both healthy and diseased dogs would provide a broader picture of antimicrobial resistance at a national level and promote prudent use of antimicrobial agents in companion animals. PMID:22516694

  19. Synthesis and serotonin transporter activity of sulphur-substituted alpha-alkyl phenethylamines as a new class of anticancer agents

    DEFF Research Database (Denmark)

    Cloonan, Suzanne M.; Keating, John J.; Butler, Stephen G.;

    2009-01-01

    The discovery that some serotonin reuptake transporter (SERT) ligands have the potential to act as pro-apoptotic agents in the treatment of cancer adds greatly to their diverse pharmacological application. 4-Methylthioamphetamine (MTA) is a selective ligand for SERT over other monoamine transport......The discovery that some serotonin reuptake transporter (SERT) ligands have the potential to act as pro-apoptotic agents in the treatment of cancer adds greatly to their diverse pharmacological application. 4-Methylthioamphetamine (MTA) is a selective ligand for SERT over other monoamine...... transporters. In this study, a novel library of structurally diverse 4-MTA analogues were synthesised with or without N-alkyl and/or C-alpha methyl or ethyl groups so that their potential SERT-dependent antiproliferative activity could be assessed. Many of the compounds displayed SERT-binding activity as well...

  20. In Vitro Activities of New and Conventional Antifungal Agents against Clinical Scedosporium Isolates

    OpenAIRE

    Meletiadis, Joseph; Meis, Jacques F. G. M.; Mouton, Johan W.; Rodriquez-Tudela, Juan Luis; Donnelly, J. Peter; Verweij, Paul E.

    2002-01-01

    The susceptibilities of 13 clinical isolates of Scedosporium apiospermum and 55 clinical isolates of S. prolificans to new and conventional drugs belonging to three different classes of antifungal agents, the azoles (miconazole, itraconazole, voriconazole, UR-9825, posaconazole), the polyenes (amphotericin B, nystatin and liposomal nystatin), and allylamines (terbinafine), were studied by use of proposed standard M38-P of NCCLS. Low growth-inhibitory antifungal activities were found in vitro ...

  1. Isolation of anticancer constituents from flos genkwa (Daphne genkwa Sieb.et Zucc.) through bioassay-guided procedures

    OpenAIRE

    Li, Simeng; Chou, Guixin; Hseu, Youcheng; Yang, Hsinling; Kwan, Hiuyee; Yu, Zhiling

    2013-01-01

    Background Flos Genkwa (yuanhua in Chinese), the dried flower buds of Daphne genkwa Sieb.et Zucc. (Thymelaeaceae), is a traditional Chinese medicinal herb mainly used for diuretic, antitussive, expectorant, and anticancer effects. However, systematic and comprehensive studies on Flos Genkwa and its bioactivity are limited. Results After confirmation of the anti-tumor activity, the 95% ethanolic extract was subjected to successive solvent partitioning to petroleum ether, dichloromethane, n-but...

  2. A novel hybrid drug between two potent anti-tubulin agents as a potential prolonged anticancer approach.

    Science.gov (United States)

    Marchetti, Paolo; Pavan, Barbara; Simoni, Daniele; Baruchello, Riccardo; Rondanin, Riccardo; Mischiati, Carlo; Feriotto, Giordana; Ferraro, Luca; Hsu, Lih-Ching; Lee, Ray M; Dalpiaz, Alessandro

    2016-08-25

    We report the design, synthesis and biological characterisation of a novel hybrid drug by conjugation of two tubulin inhibitors, a hemiasterlin derivative A (H-Mpa-Tle-Aha-OH), obtained by condensation of three non-natural amino acids, and cis-3,4',5-trimethoxy-3'aminostilbene (B). As we have previously demonstrated synergy between A and B, we used a monocarbonyl derivative of triethylene glycol as linker (L) to synthesise compounds A-L and A-L-B; via HPLC we analysed the release of its potential hydrolysis products A, A-L, B and B-L in physiological fluids: the hybrid A-L-B undergo hydrolysis in rat whole blood of the ester bond between A and L (half-life=118.2±9.5min) but not the carbamate bond between B and L; the hydrolysis product B-L was further hydrolyzed, but with a slower rate (half-life=288±12min). The compound A-L was the faster hydrolyzed conjugate (half-life=25.4±1.1min). The inhibitory activity of the compounds against SKOV3 ovarian cancer cell growth was analysed. The IC50 values were 7.48±1.27nM for A, 40.3±6.28nM for B, 738±38.5nM for A-L and 37.9±2.11nM for A-L-B. The anticancer effect of A-L-B was evidenced to be obtained via microtubule dynamics suppression. Finally, we stated the expression of the active efflux transporters P-gp (ABCB1) and MRP1 (ABCC1) in the human normal colon epithelial NCM460 cell line by reverse-transcription PCR. Via permeation studies across NCM460 monolayers we demonstrate the poor aptitude of A to interact with active efflux transporters (AET): indeed, the ratio between its permeability coefficients for the basolateral (B)→apical (A) and B→A transport was 1.5±0.1, near to the ratio of taltobulin (1.12±0.06), an hemiasterlin derivative able to elude AETs, and significantly different form the ratio of celiprolol (3.4±0.2), an AET substrate. PMID:27262542

  3. 1-Benzyl-2-methyl-3-indolylmethylene barbituric acid derivatives: Anti-cancer agents that target nucleophosmin 1 (NPM1).

    Science.gov (United States)

    Penthala, Narsimha Reddy; Ketkar, Amit; Sekhar, Konjeti R; Freeman, Michael L; Eoff, Robert L; Balusu, Ramesh; Crooks, Peter A

    2015-11-15

    In the present study, we have designed and synthesized a series of 1-benzyl-2-methyl-3-indolylmethylene barbituric acid analogs (7a-7h) and 1-benzyl-2-methyl-3-indolylmethylene thiobarbituric acid analogs (7 i-7 l) as nucleophosmin 1 (NPM1) inhibitors and have evaluated them for their anti-cancer activity against a panel of 60 different human cancer cell lines. Among these analogs 7 i, 7 j, and 7 k demonstrated potent growth inhibitory effects in various cancer cell types with GI50 values <2 μM. Compound 7 k exhibited growth inhibitory effects on a sub-panel of six leukemia cell lines with GI50 values in the range 0.22-0.35 μM. Analog 7 i also exhibited GI50 values <0.35 μM against three of the leukemia cell lines in the sub-panel. Analogs 7 i, 7 j, 7 k and 7 l were also evaluated against the mutant NPM1 expressing OCI-AML3 cell line and compounds 7 k and 7 l were found to cause dose-dependent apoptosis (AP50 = 1.75 μM and 3.3 μM, respectively). Compound 7k also exhibited potent growth inhibition against a wide variety of solid tumor cell lines: that is, A498 renal cancer (GI50 = 0.19 μM), HOP-92 and NCI-H522 lung cancer (GI50 = 0.25 μM), COLO 205 and HCT-116 colon cancer (GI50 = 0.20 and 0.26 μM, respectively), CNS cancer SF-539 (GI50 = 0.22 μM), melanoma MDA-MB-435 (GI50 = 0.22 μM), and breast cancer HS 578T (GI50 = 0.22 μM) cell lines. Molecular docking studies suggest that compounds 7 k and 7 l exert their anti-leukemic activity by binding to a pocket in the central channel of the NPM1 pentameric structure. These results indicate that the small molecule inhibitors 7 i, 7 j, 7 k, and 7 l could be potentially developed into anti-NPM1 drugs for the treatment of a variety of hematologic malignancies and solid tumors. PMID:26602084

  4. Newly Synthesized Water Soluble Cholinium-Purpurin Photosensitizers and Their Stabilized Gold Nanoparticles as Promising Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Young Key Shim

    2008-05-01

    Full Text Available For possible future use in Photodynamic Therapy (PDT and/or Photothermal Therapy (PTT of cancer and screening of cancer cells a new type of ionic liquid photosensitizer –Cholinium-Purpurin-18 (Chol-Pu-18 – was synthesized and small gold (Au nanoparticles, stabilized by this photosensitizer were prepared without adding any particular reducing agents and CTAB. UV-Vis spectroscopy and Transmission Electron Microscopy (TEM were used for characterization of the nanoparticles and FAB-MS and NMR of the ionic liquid choline hydroxide, purpurin carboxylate and their ionic liquid type of photosensitizer were obtained.

  5. Chemical genetics analysis of an aniline mustard anticancer agent reveals complex I of the electron transport chain as a target

    OpenAIRE

    Fedeles, Bogdan I.; Zhu, Angela Y.; Young, Kellie S.; Hillier, Shawn M.; Proffitt, Kyle D.; Essigmann, John M.; Croy, Robert G.

    2011-01-01

    The antitumor agent 11β (CAS 865070-37-7), consisting of a DNA-damaging aniline mustard linked to an androgen receptor (AR) ligand, is known to form covalent DNA adducts and to induce apoptosis potently in AR-positive prostate cancer cells in vitro; it also strongly prevents growth of LNCaP xenografts in mice. The present study describes the unexpectedly strong activity of 11β against the AR-negative HeLa cells, both in cell culture and tumor xenografts, and uncovers a new mechanism of action...

  6. Synthesis and biological evaluation of non-glucose glycoconjugated N-hydroyxindole class LDH inhibitors as anticancer agents

    OpenAIRE

    Di Bussolo, Valeria; Calvaresi, Emilia C.; Granchi, Carlotta; Del Bino, Linda; Frau, Ileana; Lang, Maria Chiara Dasso; Tuccinardi, Tiziano; Macchia, Marco; Martinelli, Adriano; Hergenrother, Paul J.; Minutolo, Filippo

    2015-01-01

    Inhibitors of human lactate dehydrogenase A (LDH-A) are promising therapeutic agents against cancer. The development of LDH-A inhibitors that possess cellular activities has so far proved to be particularly challenging, since the enzyme’s active site is narrow and highly polar. In the recent past, we were able to develop a glucose-conjugated N-hydroxyindole-based LDH-A inhibitor designed to exploit the sugar avidity expressed by cancer cells (the Warburg effect). Herein we describe a structur...

  7. The Study of Isolated Bacteria Application for Bioremediation Agent of Uranium Radionuclide in the Environment

    International Nuclear Information System (INIS)

    Application of the isolated bacteria on the Low Level Uranium Waste as uranium bioremediation agent in the environment has been studied. The objective of this research is to study the possibility of isolated bacteria to be used on uranium remediation process. The isolation of uranium resistance bacteria was carried out on the selective medium SBS containing 10 mg/l uranium, incubated at 37°C until the growth was visible. Selection of binding uranium bacteria was carried out based on their ability to grow on liquid medium containing various concentration of uranium that shacked on 120 rpm speed. The isolated bacteria with the highest specific growth rate constant (μ) were selected for biochemical characterization and identification by matching profile method. The result of this research showed that three selected isolate bacteria were able to grow well on liquid SBS medium until 100 mg/l uranium concentration. The identification results showed that two of them were suspected belong to the genus Pseudomonas and one isolates belong to the genus of Bacillus. The uranium reduction studied was performed by growing up the isolated bacteria on the SBS liquid medium that containing 40 mg/l uranium. Bacterial growth were measured by weighted of bacterial biomass and uranium concentration were measured by spectrophotometer. The research result showed that the selected isolates bacteria may applicable for bioremediation agent because of their ability to grow well on liquid SBS medium and their ability on uranium concentration reduction. The efficiency of reduction by Pseudomonas in the isolated bacteria one were 78.51 % and in the isolated bacteria three were 91.47 % , and Bacillus in the isolate bacteria six were 52.73%. (author)

  8. Synthesis of new secretory phospholipase A2-inhibitory indole containing isoxazole derivatives as anti-inflammatory and anticancer agents.

    Science.gov (United States)

    Pedada, Srinivasa Rao; Yarla, Nagendra Sastry; Tambade, Pawan J; Dhananjaya, Bhadrapura Lakkappa; Bishayee, Anuapam; Arunasree, Kalle M; Philip, Gundala Harold; Dharmapuri, Gangappa; Aliev, Gjumrach; Putta, Swathi; Rangaiah, Gururaja

    2016-04-13

    Secretory phospholipase A2 (sPLA2) is an important enzyme that plays a key role in various inflammatory diseases including cancer and its inhibitors have been developed as preventive or therapeutic agents. In the present study, a series of new indole containing isoxazole derivatives (10a-10o) is synthesized and evaluated for their sPLA2 inhibitory activities. All compounds (10a-10o) showed significant sPLA2 inhibition activities both in vitro and in vivo studies which is substantiated in in silico studies. Among all the tested compounds, 10o showed potent sPLA2 inhibition activity, that is comparable or more to ursolic acid (positive control). Further studies demonstrated that 10o showed in vitro antiproliferative activity when tested against MCF-7 breast and DU145 prostate cancer cells. Furthermore, compounds 10a-10o obeyed lipinsky's rule of 5 and suggesting druggable properties. The in vitro, in vivo and in silico results are encouraging and warrant pre-clinical studies to develop sPLA2-inhibitory compound 10o as novel therapeutic agent for various inflammatory disorders and several malignancies. PMID:26907155

  9. A Survey of Marine Natural Compounds and Their Derivatives with Anti-Cancer Activity Reported in 2011

    OpenAIRE

    Marc Diederich; Claudia Cerella; Marie-Hélène Teiten; Wamtinga Richard Sawadogo; Marc Schumacher; Mario Dicato

    2013-01-01

    Cancer continues to be a major public health problem despite the efforts that have been made in the search for novel drugs and treatments. The current sources sought for the discovery of new molecules are plants, animals and minerals. During the past decade, the search for anticancer agents of marine origin to fight chemo-resistance has increased greatly. Each year, several novel anticancer molecules are isolated from marine organisms and represent a renewed hope for cancer therapy. The study...

  10. 3-Bromopyruvate (3BP) a fast acting, promising, powerful, specific, and effective "small molecule" anti-cancer agent taken from labside to bedside: introduction to a special issue.

    Science.gov (United States)

    Pedersen, Peter L

    2012-02-01

    Although the "Warburg effect", i.e., elevated glucose metabolism to lactic acid (glycolysis) even in the presence of oxygen, has been recognized as the most common biochemical phenotype of cancer for over 80 years, its biochemical and genetic basis remained unknown for over 50 years. Work focused on elucidating the underlying mechanism(s) of the "Warburg effect" commenced in the author's laboratory in 1969. By 1985 among the novel findings made two related most directly to the basis of the "Warburg effect", the first that the mitochondrial content of tumors exhibiting this phenotype is markedly decreased relative to the tissue of origin, and the second that such mitochondria have markedly elevated amounts of the enzyme hexokinase-2 (HK2) bound to their outer membrane. HK2 is the first of a number of enzymes in cancer cells involved in metabolizing the sugar glucose to lactic acid. At its mitochondrial location HK2 binds at/near the protein VDAC (voltage dependent anion channel), escapes inhibition by its product glucose-6-phosphate, and gains access to mitochondrial produced ATP. As shown by others, it also helps immortalize cancer cells, i.e., prevents cell death. Based on these studies, the author's laboratory commenced experiments to elucidate the gene basis for the overexpression of HK2 in cancer. These studies led to both the discovery of a unique HK2 promoter region markedly activated by both hypoxic conditions and moderately activated by several metabolites (e.g., glucose), Also discovered was the promoter's regulation by epigenetic events (i.e., methylation, demethylation). Finally, the author's laboratory turned to the most important objective. Could they selectively and completely destroy cancerous tumors in animals? This led to the discovery in an experiment conceived, designed, and conducted by Young Ko that the small molecule 3-bromopyruvate (3BP), the subject of this mini-review series, is an incredibly powerful and swift acting anticancer agent

  11. Resistance to antimicrobial agents of Campylobacter spp. strains isolated from animals in Poland.

    Science.gov (United States)

    Krutkiewicz, A; Sałamaszyńska-Guz, A; Rzewuska, M; Klimuszko, D; Binek, M

    2009-01-01

    A total of 69 Campylobacter jejuni and 16 Campylobacter coli strains isolated from chicken, dog and pig stool samples were characterized based on their resistance to five antimicrobial agents and on plasmid pTet profiles. Antimicrobials used in this study were: amoxicillin/clavulanic acid, ciprofloxacin, erythromycin, tetracycline and trimethoprim/sulfamethoxazole. Among the isolates studied, 91.7% were resistant to one or more antimicrobial agent. The highest level of resistance for the whole test group was to trimethoprim/sulfamethoxazole (57.6%), followed by ciprofloxacin (44.2%) and tetracycline (20%). All isolates were susceptible to amoxicillin/clavulanic acid. Strains isolated from chickens were susceptible to erythromycin. Few erythromycin-resistant strains were isolated from dogs and pigs (5.8%). C. coli strains exhibited a higher antibiotic resistance than C. jejuni strains, excluding resistance to trimethoprim/sulfamethoxazole. The pTet plasmid harboring the tet(O) gene was detected in 14 Campylobacter spp. strains. Our studies demonstrate that the majority (71.4%) of tetracycline-resistant isolates carry a plasmid-borne tet(O) gene, particularly strains for which the minimum inhibitory concentration (MIC) are > or = 256 microg/ml. In conclusion, we have found high-level trimethoprim/sulfamethoxazole, ciprofloxacin and tetracycline resistance in Polish strains isolated from different sources. This study has demonstrated that resistance of Campylobacter species differs depending on both the bacterial species and animal origins. All strains that displayed resistance to four antimicrobial agents were isolated from pigs. Localization of the tet(O) gene on either plasmid or chromosome was not found to be correlated with tetracycline resistance. PMID:20169919

  12. Development of a new anti-cancer agent for targeted radionuclide therapy: β- radiolabeled RAFT-RGD

    International Nuclear Information System (INIS)

    β-emitters radiolabeled RAFT-RGD as new agents for internal targeted radiotherapy. The αvβ3 integrin is known to play an important role in tumor-induced angiogenesis, tumor proliferation, survival and metastasis. Because of its overexpression on neo-endothelial cells such as those present in growing tumors, as well as on tumor cells of various origins, αvβ3 integrin is an attractive molecular target for diagnosis and therapy of the rapidly growing and metastatic tumors. A tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK])4 (RAFT-RGD), specifically targets integrin αvβ3 in vitro and in vivo. RAFT-RGD has been used for tumor imaging and drug targeting. This study is the first to evaluate the therapeutic potential of the β-emitters radiolabeled tetrameric RGD peptide RAFT-RGD in a Nude mouse model of αvβ3 -expressing tumors. An injection of 37 MBq of 90Y-RAFT-RGD or 177Lu-RAFT-RGD in mice with αvβ3 -positive tumors caused a significant growth delay as compared with mice treated with 37 MBq of 90Y-RAFT-RAD or 177Lu-RAFT-RAD or untreated mice. In comparison, an injection of 30 MBq of 90Y-RAFT-RGD had no efficacy for the treatment of αvβ3 -negative tumors. 90Y-RAFT-RGD and 177Lu-RAFT-RGD are potent αvβ3 -expressing tumor targeting agents for internal targeted radiotherapy. (author)

  13. Screening the yeast genome for energetic metabolism pathways involved in a phenotypic response to the anti-cancer agent 3-bromopyruvate.

    Science.gov (United States)

    Lis, Paweł; Jurkiewicz, Paweł; Cal-Bąkowska, Magdalena; Ko, Young H; Pedersen, Peter L; Goffeau, Andre; Ułaszewski, Stanisław

    2016-03-01

    In this study the detailed characteristic of the anti-cancer agent 3-bromopyruvate (3-BP) activity in the yeast Saccharomyces cerevisiae model is described, with the emphasis on its influence on energetic metabolism of the cell. It shows that 3-BP toxicity in yeast is strain-dependent and influenced by the glucose-repression system. Its toxic effect is mainly due to the rapid depletion of intracellular ATP. Moreover, lack of the Whi2p phosphatase results in strongly increased sensitivity of yeast cells to 3-BP, possibly due to the non-functional system of mitophagy of damaged mitochondria through the Ras-cAMP-PKA pathway. Single deletions of genes encoding glycolytic enzymes, the TCA cycle enzymes and mitochondrial carriers result in multiple effects after 3-BP treatment. However, it can be concluded that activity of the pentose phosphate pathway is necessary to prevent the toxicity of 3-BP, probably due to the fact that large amounts of NADPH are produced by this pathway, ensuring the reducing force needed for glutathione reduction, crucial to cope with the oxidative stress. Moreover, single deletions of genes encoding the TCA cycle enzymes and mitochondrial carriers generally cause sensitivity to 3-BP, while totally inactive mitochondrial respiration in the rho0 mutant resulted in increased resistance to 3-BP. PMID:26862728

  14. A comparison of patient adherence and preference of packaging method for oral anticancer agents using conventional pill bottles versus daily pill boxes.

    Science.gov (United States)

    Macintosh, P W; Pond, G R; Pond, B J; Leung, V; Siu, L L

    2007-07-01

    Adherence to medications is an important issue in oncology due to the increasing number of anticancer agents, such as targeted therapies, formulated for oral dosing. A prospective, crossover design was utilized in which patients on capecitabine were randomly assigned to one of two packaging methods for one cycle, and then switched over to the alternate packaging method in the subsequent cycle. Twenty-five patients were accrued to this study. Adherence rates were similar when using the daily pill boxes (17/21 = 81%) and when using the conventional pill bottles (18/21 = 86%). However, more patients were satisfied with the daily pill boxes (61% versus 11%, P = 0.027), preferred the daily pill boxes (61% versus 17%, P = 0.061), and thought the daily pill boxes were more helpful in reminding them to take their medications (50% versus 11%, P = 0.070). In conclusion, this small pilot study did not demonstrate that the use of daily pill boxes improved patient adherence with capecitabine, but patient satisfaction and preference for this packaging method were greater than for the conventional pill bottles. Further exploration of this intervention in a larger study is warranted. PMID:17587364

  15. Differential cytotoxic pathways of topoisomerase I and II anticancer agents after overexpression of the E2F-1/DP-1 transcription factor complex

    DEFF Research Database (Denmark)

    Hofland, K; Petersen, B O; Falck, J;

    2000-01-01

    The transcription factor complex E2F-1/DP-1 regulates the G1-to-S-phase transition and has been associated with sensitivity to the S-phase-specific anticancer agents camptothecin and etoposide, which poison DNA topoisomerase I and II, respectively. To investigate the relationship between E2F-1 and...... drug sensitivity in detail, we established human osteosarcoma U-20S-TA cells expressing full-length E2F-1/ DP-1 under the control of a tetracycline-responsive promoter, designated UE1DP-1 cells. Topoisomerase I levels and activity as well as the number of camptothecin-induced DNA single- and double......-strand breaks were unchanged in UEIDP-1/tc- cells with >10-fold E2F-1/DP-1 overexpression. However, UE1DP-1/tc- cells were hypersensitive to camptothecin in both a clonogenic assay and four different apoptotic assays. This indicates that camptothecin-induced toxicity in this model is due to the activation of an...

  16. Systematic Analysis of the Anticancer Agent Taxol-Producing Capacity in Colletotrichum Species and Use of the Species for Taxol Production

    Science.gov (United States)

    Choi, Jinhee; Park, Jae Gyu; Ali, Md. Sarafat

    2016-01-01

    Paclitaxel (taxol) has long been used as a potent anticancer agent for the treatment of many cancers. Ever since the fungal species Taxomyces andreanae was first shown to produce taxol in 1993, many endophytic fungal species have been recognized as taxol accumulators. In this study, we analyzed the taxol-producing capacity of different Colletotrichum spp. to determine the distribution of a taxol biosynthetic gene within this genus. Distribution of the taxadiene synthase (TS) gene, which cyclizes geranylgeranyl diphosphate to produce taxadiene, was analyzed in 12 Colletotrichum spp., of which 8 were found to contain the unique skeletal core structure of paclitaxel. However, distribution of the gene was not limited to closely related species. The production of taxol by Colletotrichum dematium, which causes pepper anthracnose, depended on the method in which the fungus was stored, with the highest production being in samples stored under mineral oil. Based on its distribution among Colletotrichum spp., the TS gene was either integrated into or deleted from the bacterial genome in a species-specific manner. In addition to their taxol-producing capacity, the simple genome structure and easy gene manipulation of these endophytic fungal species make them valuable resources for identifying genes in the taxol biosynthetic pathway. PMID:27433121

  17. 6-125I-iodo-2-methyl-1,4-naphthoquinol bis (diammonium phosphate) as a potential radio-halogenated anti-cancer agent

    International Nuclear Information System (INIS)

    6-125I-iodo-2-methyl-1,4-naphthoquinol bis (diammonium phosphate) (6-125I-iodo-MNDP) has been synthesised and studied as the prototype of a class of potential radio-halogenated anti-cancer agents. The incorporated 125I provides Auger electron radiations which behave like high LET radiations in the treatment of tumours, though the accompanying X- and γ-radiations make an undersirable contribution to the total body dose. The in vitro experiments reported show that 6-125I-iodo-MNDP is selectively concentrated in the cells of some human malignant tumours by factor of about 15 to 20 or more in relation to the cells of normal origin studied. On the basis of dosimetric considerations and comparison with clinical treatment with tritiated methylnaphthoquinol diphosphate, practical dosage of 6-125I-iodo-MNDP is suggested and clinical indications and safety of use are discussed. The types of tumour of particular interest are inoperable cases of carcinoma of the colon, carcinoma of the pancreas, malignant melanoma and osteosarcoma. Further investigations are in progress. (orig.)

  18. A potential anticancer agent: 5-chloro-7-iodo-8-hydroxyquinolinium dichlorido(5-chloro-7-iodoquinolin-8-olato-κ2N,Opalladium(II dihydrate

    Directory of Open Access Journals (Sweden)

    Peter Vranec

    2011-11-01

    Full Text Available The title PdII coordination compound, (C9H6ClINO[PdCl2(C9H4ClINO]·2H2O, was prepared as a potential anticancer agent. Its structure is ionic and consists of a square-planar [PdCl2(CQ]− complex anion (CQ is 5-chloro-7-iodoquinolin-8-olate, with the PdII atom surrounded by two chloride ligands in a cis configuration and one N,O-bidentate CQ molecule, a protonated anion of CQ as counter-cation and two non-coordinated water molecules. The water molecules are involved in O—H...O and N—H...O hydrogen bonds, which interconnect the HCQ+ cations into a chain parallel to [010]. Apart from these interactions, the structure is also stabilized by face-to-face π–π interactions [centroid–centroid = 3.546 (3 Å], which occur between the phenolic parts of the complex anions and cations.

  19. 1C-gene array for toxic response using RNA isolated from HepG2 cells treated with anticancer drugs

    Science.gov (United States)

    Hong, Yulong; Bao, Yijia P.; Xie, Xinying; Mooney, Jeffrey L.; Mueller, Uwe R.; Lai, Fang

    2002-06-01

    The possibility of using microarray technology for mechanistic understanding of drug toxicity has opened up a new research field in Toxicology. In an attempt to build knowledge in the field, we have designed a 1C-gene array composed of 85 known human genes with toxicological interests and 15 control genes. HepG2 cells were treated with ethanol and two anticancer drugs, mitomycin C and doxorubicin. RNA were isolated and labeled by fluorescent dyes, then hybridized to the 1C-gene array. Our results showed that a number of cytochrome P450 genes, such as CYP4F2/3, CYP3A3, CYP24, and CYP51, were consistently responsive to the toxicant treatment. However, different genes response to different toxicants. For example, CYP24 and CYP51 were up regulated by the ethanol treatment but remained unresponsive to the other two drugs. The anticancer drugs, but not ethanol differentially regulated several other genes including CYP3A3, TNFRSF6 and CHES1, implying that the two drugs might function through a similar mechanism, which differs from that of ethanol. The reproducibility of our results suggests that microarray- based expression analysis may offer a rapid and efficient means of assessing drug toxicity.

  20. Fucoidan Extract Enhances the Anti-Cancer Activity of Chemotherapeutic Agents in MDA-MB-231 and MCF-7 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Zhongyuan Zhang

    2013-01-01

    Full Text Available Fucoidan, a fucose-rich polysaccharide isolated from brown alga, is currently under investigation as a new anti-cancer compound. In the present study, fucoidan extract (FE from Cladosiphon navae-caledoniae Kylin was prepared by enzymatic digestion. We investigated whether a combination of FE with cisplatin, tamoxifen or paclitaxel had the potential to improve the therapeutic efficacy of cancer treatment. These co-treatments significantly induced cell growth inhibition, apoptosis, as well as cell cycle modifications in MDA-MB-231 and MCF-7 cells. FE enhanced apoptosis in cancer cells that responded to treatment with three chemotherapeutic drugs with downregulation of the anti-apoptotic proteins Bcl-xL and Mcl-1. The combination treatments led to an obvious decrease in the phosphorylation of ERK and Akt in MDA-MB-231 cells, but increased the phosphorylation of ERK in MCF-7 cells. In addition, we observed that combination treatments enhanced intracellular ROS levels and reduced glutathione (GSH levels in breast cancer cells, suggesting that induction of oxidative stress was an important event in the cell death induced by the combination treatments.

  1. Isolation, characterization, and identification of biological control agent for potato soft rot in Bangladesh.

    Science.gov (United States)

    Rahman, M M; Ali, M E; Khan, A A; Akanda, A M; Uddin, Md Kamal; Hashim, U; Abd Hamid, S B

    2012-01-01

    A total of 91 isolates of probable antagonistic bacteria of potato soft rot bacterium Erwinia carotovora subsp. carotovora (Ecc) were extracted from rhizospheres and endophytes of various crop plants, different soil varieties, and atmospheres in the potato farming areas of Bangladesh. Antibacterial activity of the isolated probable antagonistic bacteria was tested in vitro against the previously identified most common and most virulent soft rot causing bacterial strain Ecc P-138. Only two isolates E-45 and E-65 significantly inhibited the in vitro growth of Ecc P-138. Physiological, biochemical, and carbon source utilization tests identified isolate E-65 as a member of the genus Bacillus and the isolate E-45 as Lactobacillus sp. The stronger antagonistic activity against Ecc P-138 was found in E-65 in vitro screening and storage potatoes. E-65 reduced the soft rot infection to 22-week storage potatoes of different varieties by 32.5-62.5% in model experiment, demonstrating its strong potential to be used as an effective biological control agent for the major pectolytic bacteria Ecc. The highest (62.5%) antagonistic effect of E-65 was observed in the Granola and the lowest (32.7%) of that was found in the Cardinal varieties of the Bangladeshi potatoes. The findings suggest that isolate E-65 could be exploited as a biocontrol agent for potato tubers. PMID:22645446

  2. Caffeine-based gold(I) N-heterocyclic carbenes as possible anticancer agents: synthesis and biological properties.

    Science.gov (United States)

    Bertrand, Benoît; Stefan, Loic; Pirrotta, Marc; Monchaud, David; Bodio, Ewen; Richard, Philippe; Le Gendre, Pierre; Warmerdam, Elena; de Jager, Marina H; Groothuis, Geny M M; Picquet, Michel; Casini, Angela

    2014-02-17

    A new series of gold(I) N-heterocyclic carbene (NHC) complexes based on xanthine ligands have been synthesized and characterized by mass spectrometry, NMR, and X-ray diffraction. The compounds have been tested for their antiproliferative properties in human cancer cells and nontumorigenic cells in vitro, as well as for their toxicity in healthy tissues ex vivo. The bis-carbene complex [Au(caffein-2-ylidene)2][BF4] (complex 4) appeared to be selective for human ovarian cancer cell lines and poorly toxic in healthy organs. To gain preliminary insights into their actual mechanism of action, two biologically relevant in cellulo targets were studied, namely, DNA (more precisely a higher-order DNA structure termed G-quadruplex DNA that plays key roles in oncogenetic regulation) and a pivotal enzyme of the DNA damage response (DDR) machinery (poly-(adenosine diphosphate (ADP)-ribose) polymerase 1 (PARP-1), strongly involved in the cancer resistance mechanism). Our results indicate that complex 4 acts as an efficient and selective G-quadruplex ligand while being a modest PARP-1 inhibitor (i.e., poor DDR impairing agent) and thus provide preliminary insights into the molecular mechanism that underlies its antiproliferative behavior. PMID:24499428

  3. New Oxidovanadium Complexes Incorporating Thiosemicarbazones and 1, 10-Phenanthroline Derivatives as DNA Cleavage, Potential Anticancer Agents, and Hydroxyl Radical Scavenger.

    Science.gov (United States)

    Ying, Peng; Zeng, Pengfei; Lu, Jiazheng; Chen, Hongyuan; Liao, Xiangwen; Yang, Ning

    2015-10-01

    Four novel oxidovanadium(IV) complexes, [VO(hntdtsc)(PHIP)] (1) (hntdtsc = 2-hydroxy-1-naphthaldehyde thiosemicarbazone, PHIP= 2-phenyl-imidazo[4,5-f]1,10-phenanthroline), [VO(hntdtsc)(DPPZ)](2)(DPPZ= dipyrido[3,2-a:2',3'-c]phenazine), [VO(satsc)(PHIP)](3) (satsc=salicylaldehyde thiosemicarbazone), and [VO(satsc)(DPPZ)](4), have been prepared and characterized. The chemical nuclease activities and photocleavage reactions of the complexes were tested. All four complexes can efficiently cleave pBR322 DNA, and complex 1 has the best cleaving ability. The antitumor properties of these complexes were examined with three different tumor cell lines using MTT assay. Their antitumor mechanism has been analyzed using cell cycle analysis, fluorescence microscopy of apoptosis, and Annexin V-FITC/PI assay. The results showed that the growth of human neuroblastoma (SH-SY5Y, SK-N-SH) and human breast adenocarcinoma (MCF-7) cells were inhibited significantly with very low IC50 values. Complex 1 was found to be the most potent antitumor agent among the four complexes. It can cause G0/G1 phase arrest of the cell cycle and exhibited significant induced apoptosis in SK-N-SH cells and displayed typical morphological apoptotic characteristics. In addition, they all displayed reasonable abilities to scavenge hydroxyl radical, and complex 1 was the best inhibitor. PMID:25659415

  4. Evaluation of SD-208, a TGF-β-RI Kinase Inhibitor, as an Anticancer Agent in Retinoblastoma.

    Science.gov (United States)

    Fadakar, Puran; Akbari, Abolfazl; Ghassemi, Fariba; Mobini, Gholam Reza; Mohebi, Masoumeh; Bolhassani, Manzar; Abed Khojasteh, Hoda; Heidari, Mansour

    2016-06-01

    Retinoblastoma is the most common intraocular tumor in children resulting from genetic alterations and transformation of mature retinal cells. The objective of this study was to investigate the effects of SD-208, TGF-β-RI kinase inhibitor, on the expression of some miRNAs including a miR-17/92 cluster in retinoblastoma cells. Prior to initiate this work, the cell proliferation was studied by Methyl Thiazolyl Tetrazolium (MTT) and bromo-2'-deoxyuridine (BrdU) assays. Then, the expression patterns of four miRNAs (18a, 20a, 22, and 34a) were investigated in the treated SD-208 (0.0, 1, 2 and 3 µM) and untreated Y-79 cells. A remarkable inhibition of the cell proliferation was found in Y-79 cells treated with SD-208 versus untreated cells. Also, the expression changes were observed in miRNAs 18a, 20a, 22 and 34a in response to SD-208 treatment (Pretinoblastoma cell line. To the best of the researchers' knowledge, this is the first report demonstrating that the SD-208 could alter the expression of tumor suppressive miRNAs as well as oncomiRs in vitro. In conclusion, the present data suggest that SD-208 could be an alternative agent in retinoblastoma treatment. PMID:27306340

  5. Using immunoadjuvant agent glycated chitosan to enhance anti-cancer stem like cell immunity induced by HIFU

    Science.gov (United States)

    Chen, Y.-L.; Chen, W.-R.; Liu, R.-S.; Yang, F.-Y.; Wang, C.-Y.; Lee, Y.-J.

    2013-02-01

    Thermal therapy is based on the observation that tumor cells are sensitive to increased temperature, which is important for tumor control. In this study, the high intensity focused ultrasound (HIFU) system was used to simulate thermal therapy on breast cancer control in the small animal model. Additionally, the immunoadjuvant agent, so called glycated chitosan (GC), was used to enhance the immunological effects on tumor control. The bioluminescent imaging showed that tumor metastasis was apparently suppressed by a combined treatment using HIFU and GC, but not in HIFU or GC alone. Using immunohistochemical (IHC) staining, lung metastasis of 4T1-3R tumor cells further agree the observations obtained from non-invasive in vivo imaging. We also found that plasma collected from mice treated with combined HIFU and GC could significantly suppress the viability of cultured 4T1 cells compared to untreated or single treated group. In summary, these results suggest that the HIFU therapy combined with GC can enhance the tumor immunogenicity and tumor control.

  6. Design, synthesis and structural studies of meta-xylyl linked bis-benzimidazolium salts: potential anticancer agents against ‘human colon cancer’

    Directory of Open Access Journals (Sweden)

    Haque Rosenani A

    2012-07-01

    Full Text Available Abstract Background Benzimidazole derivatives are structurally bioisosteres of naturally occurring nucleotides, which makes them compatible with biopolymers of living systems. This property gives benzimidazole a biological and clinical importance. In the last decade, this class of compounds has been reported to possess anti-allergic, anti-diabatic, anti-HIV, anti-hypertensive, anti-inflammatory, anti-mycobacterial, anti-oxidant, anti-protozoal, and anti-viral properties. The researchers are now interested to explore their potential as anti-cancer agents. In the present study, an effort was made to further explore this area of research. Furthermore, in order to increase the solubility and efficacy of these heterocycles, the interest is now shifted to the salts of these compounds. With this background, we planned to synthesize a series of meta-xylyl linked bis-benzimidazolium salts to assess their anti-proliferation efficacy on human colon cancer cell line (HCT 116. Results A number of N-alkylbenzimidazoles were synthesized by reactions of benzimidazole with alkyl halides (i-PrBr, PrBr, EthBr, Pent-2-ylBr, BuBr, BenzCl, HeptBr. The subsequent treatment of the resulting N-alkylbenzimidazoles with 1,3-(bromomethylenebenzene afforded corresponding bis-benzimidazolium salts. All synthesized compounds were characterized by spectroscopic techniques (Additional file 1: NMR & FT-IR and microanalysis. Molecular structures of selected compounds were established through single crystal x-ray diffraction studies. All the compounds were assessed for their anti-proliferation test on human colorectal cancer cell line (HCT 116. Results showed that the compounds exhibited dose dependent cytotoxicity towards the colon cancer cells with IC50 ranges between 0.1 to 17.6 μM. The anti-proliferation activity of all compounds was more pronounced than that of standard reference drug 5-flourouracil (IC50 =19.2 μM. Conclusions All the synthesized bis-benzimidazolium salts

  7. Synthesis and biological activities of transition metal complexes based on acetylsalicylic acid as neo-anticancer agents.

    Science.gov (United States)

    Rubner, Gerhard; Bensdorf, Kerstin; Wellner, Anja; Kircher, Brigitte; Bergemann, Silke; Ott, Ingo; Gust, Ronald

    2010-10-14

    [(μ(4)-η(2))-(Prop-2-ynyl)-2-acetoxybenzoate]dicobalthexacarbonyl (Co-ASS), a derivative of aspirin (ASS), demonstrated high growth-inhibitory potential against various tumor cells with interference in the arachidonic acid cascade as probable mode of action. The significance of the kind of metal and cluster was verified in this structure-activity study: Co(2)(CO)(6) was respectively exchanged by a tetrameric cobalt-, trimeric ruthenium-, or trimeric ironcarbonyl cluster. Furthermore, the metal binding motif was changed from alkyne to 1,3-butadiene. Compounds were evaluated for growth inhibition, antiproliferative effects, and apoptosis induction in breast (MCF-7, MDA-MB 231) and colon cancer (HT-29) cell lines and for COX-1/2 inhibitory effects at isolated isoenzymes. Additionally, the major COX metabolite prostaglandin E2 (PGE(2)) was quantified in arachidonic acid-stimulated MDA-MB 231 breast tumor cells. It was demonstrated that the metal cluster was of minor importance for effects on cellular activity if an alkyne was used as ligand. Generally, no correlation existed between growth inhibition and COX activity. Cellular growth inhibition and antiproliferative activity at higher concentrations of the most active compounds Prop-ASS-Co(4) and Prop-ASS-Ru(3) correlated well with apoptosis induction. PMID:20857911

  8. Bacterial Agents Isolated from Wards’ Environment and Staff’s Hands in Yahyanejad Hospital, Babol

    Directory of Open Access Journals (Sweden)

    Sadighian, F. (BSc

    2013-01-01

    Full Text Available Background and Objective: Nowadays, nosocomial infection is one of the greatest problems in hospitals. Normal flora of staff’s hands and the bacterial agents on the surface of medical equipment can become progressively colonized with potential pathogens during patient care. This study was carried out to determine the bacterial agents existed on staff’s hands and in the wards of hospital to step in to control nosocomial infection. Material and Methods: In this descriptive study, during 17 months (22.mar.2010- 30.aug.2011, 403 samples, using sterile swab , were randomly obtained from the staff’s hands and medical equipment of emergency departments , ICU, male operation room and female surgical unit . The samples were cultured on Blood agar (BA and Eosin methylene blue (EMB. Then, identification of isolated bacteria was done with diagnostic tests. Results: Of 430 samples, 530 bacteria were isolated from staff’s hands (N= 291 and medical equipment (N= 234. The most common bacterium from personnel’s hands (144; 49.5% and medical equipment (24; 10% is Staphylococcus aureus. Also, three isolates of pseudomonas aeruginosa from staff’s hands of male surgical ward and medical equipment of ICU, and two isolates of Acinetobacter.spp from ICU’s medical equipment were identified. Conclusion: With regard to the findings, it seems that applying the appropriate disinfectant agents by using standard procedures is necessary. Keywords: Medical Equipment; Staff’s Hand; Nosocomial Infection; Staphylococcus Aureus

  9. Production of a newly isolated Paenibacillus polymyxa biocontrol agent using monosodium glutamate wastewater and potato wastewater.

    Science.gov (United States)

    Gu, Likun; Bai, Zhihui; Jin, Bo; Zhang, Jianyun; Li, Wenying; Zhuang, Guoqiang; Zhang, Hongxun

    2010-01-01

    A phyllosphere bacterial strain EBL-06 was isolated from wheat leaves. The morphology, cultural characteristics, phospholipid fatty acids, physiological and antagonistic fungus activities of this strain were investigated. A phylogenetic tree was constructed by comparing with the published 16S rDNA sequences of the relevant bacteria. The results showed that the isolate EBL-06 was a strain of Paenibacillus polymyxa; this strain performed a high level of antagonistic fungus activity toward a broad spectrum of phytopathogens, such as Botrytis cinerea, Cladosporium cucumerinum, Fusarium spp. The isolate EBL-06 can grow well using monosodium glutamate wastewater (MGW) and potato wastewater (PW) as culture medium. The maximum yield of 6.5 x 10(9) CFU/mL of the isolate EBL-06 anti-fungus biocontrol agent was reached in 15 hr cultivation at 28 degrees C, pH 6.0-7.5 using the mixture of MGW and PW (1:9). PMID:21174972

  10. The Anticancer Agent Di-2-pyridylketone 4,4-Dimethyl-3-thiosemicarbazone (Dp44mT) Overcomes Prosurvival Autophagy by Two Mechanisms

    Science.gov (United States)

    Gutierrez, Elaine; Richardson, Des R.; Jansson, Patric J.

    2014-01-01

    Autophagy functions as a survival mechanism during cellular stress and contributes to resistance against anticancer agents. The selective antitumor and antimetastatic chelator di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) causes lysosomal membrane permeabilization and cell death. Considering the integral role of lysosomes in autophagy and cell death, it was important to assess the effect of Dp44mT on autophagy to further understand its mechanism of action. Notably, Dp44mT affected autophagy by two mechanisms. First, concurrent with its antiproliferative activity, Dp44mT increased the expression of the classical autophagic marker LC3-II as a result of induced autophagosome synthesis. Second, this effect was supplemented by a reduction in autophagosome degradation as shown by the accumulation of the autophagic substrate and receptor p62. Conversely, the classical iron chelator desferrioxamine induced autophagosome accumulation only by inhibiting autophagosome degradation. The formation of redox-active iron or copper Dp44mT complexes was critical for its dual effect on autophagy. The cytoprotective antioxidant N-acetylcysteine inhibited Dp44mT-induced autophagosome synthesis and p62 accumulation. Importantly, Dp44mT inhibited autophagosome degradation via lysosomal disruption. This effect prevented the fusion of lysosomes with autophagosomes to form autolysosomes, which is crucial for the completion of the autophagic process. The antiproliferative activity of Dp44mT was suppressed by Beclin1 and ATG5 silencing, indicating the role of persistent autophagosome synthesis in Dp44mT-induced cell death. These studies demonstrate that Dp44mT can overcome the prosurvival activity of autophagy in cancer cells by utilizing this process to potentiate cell death. PMID:25301941

  11. Genome-wide functional genetic screen with the anticancer agent AMPI-109 identifies PRL-3 as an oncogenic driver in triple-negative breast cancers.

    Science.gov (United States)

    Gari, Hamid H; Gearheart, Christy M; Fosmire, Susan; DeGala, Gregory D; Fan, Zeying; Torkko, Kathleen C; Edgerton, Susan M; Lucia, M Scott; Ray, Rahul; Thor, Ann D; Porter, Christopher C; Lambert, James R

    2016-03-29

    Triple-negative breast cancers (TNBC) are among the most aggressive and heterogeneous cancers with a high propensity to invade, metastasize and relapse. Here, we demonstrate that the anticancer compound, AMPI-109, is selectively efficacious in inhibiting proliferation and inducing apoptosis of multiple TNBC subtype cell lines as assessed by activation of pro-apoptotic caspases-3 and 7, PARP cleavage and nucleosomal DNA fragmentation. AMPI-109 had little to no effect on growth in the majority of non-TNBC cell lines examined. We therefore utilized AMPI-109 in a genome-wide shRNA screen in the TNBC cell line, BT-20, to investigate the utility of AMPI-109 as a tool in helping to identify molecular alterations unique to TNBC. Our screen identified the oncogenic phosphatase, PRL-3, as a potentially important driver of TNBC growth, migration and invasion. Through stable lentiviral knock downs and transfection with catalytically impaired PRL-3 in TNBC cells, loss of PRL-3 expression, or functionality, led to substantial growth inhibition. Moreover, AMPI-109 treatment, downregulation of PRL-3 expression or impairment of PRL-3 activity reduced TNBC cell migration and invasion. Histological evaluation of human breast cancers revealed PRL-3 was significantly, though not exclusively, associated with the TNBC subtype and correlated positively with regional and distant metastases, as well as 1 and 3 year relapse free survival. Collectively, our study is proof-of-concept that AMPI-109, a selectively active agent against TNBC cell lines, can be used as a molecular tool to uncover unique drivers of disease progression, such as PRL-3, which we show promotes oncogenic phenotypes in TNBC cells. PMID:26909599

  12. Câncer e agentes antineoplásicos ciclo-celular específicos e ciclo-celular não específicos que interagem com o DNA: uma introdução Cancer and cell cicle-specific and cell cicle nonspecific anticancer DNA-interactive agents: an introduction

    Directory of Open Access Journals (Sweden)

    Vera Lúcia de Almeida

    2005-02-01

    Full Text Available The chemotherapy agents against cancer may be classified as "cell cycle-specific" or "cell cycle-nonspecific". Nevertheless, several of them have their biological activity related to any kind of action on DNA such as: antimetabolic agents (DNA synthesis inhibition, inherently reactive agents (DNA alkylating electrophilic traps for macromolecular nucleophiles from DNA through inter-strand cross-linking - ISC - alkylation and intercalating agents (drug-DNA interactions inherent to the binding made due to the agent penetration in to the minor groove of the double helix. The earliest and perhaps most extensively studied and most heavily employed clinical anticancer agents in use today are the DNA inter-strand cross-linking agents.

  13. Using XML to Help Isolate Software Systems and Agents from Change Due to Communications

    Directory of Open Access Journals (Sweden)

    Paul Darbyshire

    2014-09-01

    Full Text Available Development and research into distributed and agent based systems has grown enormously over the last few years, and the number of practical applications for such systems has grown along with it as the technology and infrastructure improves to accommodate such systems. As with all systems, evolution and change is inevitable, but with the growth of distributed systems and the Service Oriented Architecture, we have another dimension of change we need to consider; that of communication. The importance of the role of communication between these systems has been highlighted by many researchers, particularly for multi-agent systems and for distributed communicating agents. But the form of such communication often remains a mystery. Communication aspects are often dependent on other factors within an architectural framework, particularly the data. In order to reduce unnecessary changes to the communication aspects of a system, we need to insulate the communication as much as possible from consequential change effected by architectural other framework elements. A message system using an XML-type syntax is more extensible and adaptable for use in a changing environment. It helps to isolate the communication from the structure and content of the message, thereby reducing consequential change. This paper discusses the use of XML for the construction of agent-based messages, and presents a simple approach for the deconstruction of messages by receiving agents.

  14. Anticancer Agents Targeted to Sirtuins

    Directory of Open Access Journals (Sweden)

    Tomohiro Kozako

    2014-12-01

    Full Text Available Sirtuins are nicotinamide adenine dinucleotide+-dependent deacetylases of which there are seven isoforms (SIRT1–7. Sirtuin activity is linked to gene expression, lifespan extension, neurodegeneration, and age-related disorders. Numerous studies have suggested that sirtuins could be of great significance with regard to both antiaging and tumorigenesis, depending on its targets in specific signaling pathways or in specific cancers. Recent studies have identified small chemical compounds that modulate sirtuins, and these modulators have enabled a greater understanding of the biological function and molecular mechanisms of sirtuins. This review highlights the possibility of sirtuins, especially SIRT1 and SIRT2, for cancer therapy targets, and focuses on the therapeutic potential of sirtuin modulators both in cancer prevention and treatment.

  15. Anticancer Agents Targeted to Sirtuins

    OpenAIRE

    Tomohiro Kozako; Takayoshi Suzuki; Makoto Yoshimitsu; Naomichi Arima; Shin-ichiro Honda; Shinji Soeda

    2014-01-01

    Sirtuins are nicotinamide adenine dinucleotide+-dependent deacetylases of which there are seven isoforms (SIRT1–7). Sirtuin activity is linked to gene expression, lifespan extension, neurodegeneration, and age-related disorders. Numerous studies have suggested that sirtuins could be of great significance with regard to both antiaging and tumorigenesis, depending on its targets in specific signaling pathways or in specific cancers. Recent studies have identified small chemical compounds that m...

  16. Isolation and Utilization of Corn Cobs Hemisellulose as Chelating Agent for Lead Ions

    International Nuclear Information System (INIS)

    Corn cobs is an agricultural byproduct containing polysaccharide composed of cellulose, hemicelluloses and lignin. Hemicelluloses has a hydroxyl and carbonyl functional groups which can be used as chelating agent for metal ions. The purpose of this study was to isolate and evaluate corncobs hemicelluloses as a chelating agent toward lead ion. Graphite furnace spectrophotometry at 283.3 nm was used to determine the residual lead ion in solution. The research's result showed that the highest yield of hemicelluloses (12.04 %) was obtained from delignication with 0,03 M NaOH in 60 % ethanol and 3 % H2O2, hemicelluloses isolation with 500 ml of 0.2 M NaOH, and precipitation with 1:4 ratio of 10 % acetic acid in 95 % ethanol. The 300 mg corn cobs hemicelluloses has chelating effect for 40 mg lead solution at (39.52±0.1350) mg or 98.80 %, that the corn cobs hemicelluloses can be used as a chelating agent for lead. (author)

  17. Evaluation of Beauveria bassiana (Hyphomycetes) isolates as potential agents for control of Dendroctonus valens

    Institute of Scientific and Technical Information of China (English)

    Long-Wa Zhang; Yu-Jun Liu; Jian Yao; Bin Wang; Bo Huang; Zeng-Zhi Li; Mei-Zhen Fan; Jiang-Hua Sun

    2011-01-01

    The red turpentine beetle (RTB), Dendroctonus valens LeConte, as a destructive invasive pest, has become one of the most economically important forest pest in China. Effective control measures are desperately needed. Entomopathogenic fungi, such as Beauveria bassiana, have shown great potential for the management of some bark beetle species. In this study, 12 isolates of B. bassiana from bark beetle were examined for biological characteristics and virulence, to assess their potential as biocontrol agents for RTB. There were significant differences (at P = 0.05) in colony growth rate, conidial yield, conidial germination, tolerance to UV light and extracellular proteases activity among the tested B. bassiana isolates. Isolates, including Bbl801, Bbl906, Bb789 and Bb773, exhibited the best characteristics, because they have faster hyphal growth rate, higher spore production and faster spore germination, higher UV tolerance and protease (Prl) production. The results of a pathogenicity test of B. bassiana on RTB larvae showed that most isolates of B. bassiana have demonstrated high efficacy and the highest virulent isolate was Bbl801, which killed 100% of the treated insects and had a median lethal time (LT50) of 4.60 days at a concentration of 1× 107 conidia/mL. Therefore, isolate Bb 1801 has a great potential for sustainable control of RTB in the forest. The correlation between biological characteristics and virulence of the fungal isolates is discussed and the possibility of combination of entomopathogenic fungi with semiochemicals, as one of the promising strategy for RTB control, is considered.

  18. Sesterterpenoids with Anticancer Activity.

    Science.gov (United States)

    Evidente, Antonio; Kornienko, Alexander; Lefranc, Florence; Cimmino, Alessio; Dasari, Ramesh; Evidente, Marco; Mathieu, Véronique; Kiss, Robert

    2015-01-01

    Terpenes have received a great deal of attention in the scientific literature due to complex, synthetically challenging structures and diverse biological activities associated with this class of natural products. Based on the number of C5 isoprene units they are generated from, terpenes are classified as hemi- (C5), mono- (C10), sesqui- (C15), di- (C20), sester- (C25), tri (C30), and tetraterpenes (C40). Among these, sesterterpenes and their derivatives known as sesterterpenoids, are ubiquitous secondary metabolites in fungi, marine organisms, and plants. Their structural diversity encompasses carbotricyclic ophiobolanes, polycyclic anthracenones, polycyclic furan-2-ones, polycyclic hydroquinones, among many other carbon skeletons. Furthermore, many of them possess promising biological activities including cytotoxicity and the associated potential as anticancer agents. This review discusses the natural sources that produce sesterterpenoids, provides sesterterpenoid names and their chemical structures, biological properties with the focus on anticancer activities and literature references associated with these metabolites. A critical summary of the potential of various sesterterpenoids as anticancer agents concludes the review. PMID:26295461

  19. Oral delivery of anticancer drugs

    DEFF Research Database (Denmark)

    Thanki, Kaushik; Gangwal, Rahul P; Sangamwar, Abhay T;

    2013-01-01

    The present report focuses on the various aspects of oral delivery of anticancer drugs. The significance of oral delivery in cancer therapeutics has been highlighted which principally includes improvement in quality of life of patients and reduced health care costs. Subsequently, the challenges...... incurred in the oral delivery of anticancer agents have been especially emphasized. Sincere efforts have been made to compile the various physicochemical properties of anticancer drugs from either literature or predicted in silico via GastroPlus™. The later section of the paper reviews various emerging...... trends to tackle the challenges associated with oral delivery of anticancer drugs. These invariably include efflux transporter based-, functional excipient- and nanocarrier based-approaches. The role of drug nanocrystals and various others such as polymer based- and lipid based-nanocarriers in the...

  20. Isolation and characterization of soil Streptomyces species as potential biological control agents against fungal plant pathogens.

    Science.gov (United States)

    Evangelista-Martínez, Zahaed

    2014-05-01

    The use of antagonist microorganisms against fungal plant pathogens is an attractive and ecologically alternative to the use of chemical pesticides. Streptomyces are beneficial soil bacteria and potential candidates for biocontrol agents. This study reports the isolation, characterization and antagonist activity of soil streptomycetes from the Los Petenes Biosphere Reserve, a Natural protected area in Campeche, Mexico. The results showed morphological, physiological and biochemical characterization of six actinomycetes and their inhibitory activity against Curvularia sp., Aspergillus niger, Helminthosporium sp. and Fusarium sp. One isolate, identified as Streptomyces sp. CACIS-1.16CA showed the potential to inhibit additional pathogens as Alternaria sp., Phytophthora capsici, Colletotrichum sp. and Rhizoctonia sp. with percentages ranging from 47 to 90 %. This study identified a streptomycete strain with a broad antagonist activity that could be used for biocontrol of plant pathogenic fungi. PMID:24310522

  1. In vitro activities of 10 antimicrobial agents against bacterial vaginosis-associated anaerobic isolates from pregnant Japanese and Thai women.

    OpenAIRE

    Puapermpoonsiri, S; Watanabe, K; Kato, N; K. Ueno

    1997-01-01

    The in vitro activities of 10 antimicrobial agents against 159 bacterial vaginosis-associated anaerobic isolates from pregnant Japanese and Thai women were determined. Clindamycin, imipenem, cefmetazole, amoxicillin, amoxicillin-clavulanate, and metronidazole were highly active against all anaerobic isolates except Prevotella bivia and Mobiluncus species, which were resistant to amoxicillin and metronidazole, respectively. Cefotiam, ceftazidime, and ofloxacin were variably effective, while ce...

  2. Could the FDA-approved anti-HIV PR inhibitors be promising anticancer agents? An answer from enhanced docking approach and molecular dynamics analyses

    Directory of Open Access Journals (Sweden)

    Arodola OA

    2015-11-01

    Full Text Available Olayide A Arodola, Mahmoud ES SolimanMolecular Modelling and Drug Design Lab, School of Health Sciences, Westville Campus, University of KwaZulu-Natal, Durban, South AfricaAbstract: Based on experimental data, the anticancer activity of nelfinavir (NFV, a US Food and Drug Administration (FDA-approved HIV-1 protease inhibitor (PI, was reported. Nevertheless, the mechanism of action of NFV is yet to be verified. It was hypothesized that the anticancer activity of NFV is due to its inhibitory effect on heat shock protein 90 (Hsp90, a promising target for anticancer therapy. Such findings prompted us to investigate the potential anticancer activity of all other FDA-approved HIV-1 PIs against human Hsp90. To accomplish this, “loop docking” – an enhanced in-house developed molecular docking approach – followed by molecular dynamic simulations and postdynamic analyses were performed to elaborate on the binding mechanism and relative binding affinities of nine FDA-approved HIV-1 PIs against human Hsp90. Due to the lack of the X-ray crystal structure of human Hsp90, homology modeling was performed to create its 3D structure for subsequent simulations. Results showed that NFV has better binding affinity (ΔG =−9.2 kcal/mol when compared with other PIs: this is in a reasonable accordance with the experimental data (IC50 3.1 µM. Indinavir, saquinavir, and ritonavir have close binding affinity to NFV (ΔG =−9.0, −8.6, and −8.5 kcal/mol, respectively. Per-residue interaction energy decomposition analysis showed that hydrophobic interaction (most importantly with Val534 and Met602 played the most predominant role in drug binding. To further validate the docking outcome, 5 ns molecular dynamic simulations were performed in order to assess the stability of the docked complexes. To our knowledge, this is the first account of detailed computational investigations aimed to investigate the potential anticancer activity and the binding

  3. Potential Activity of Basil Plants as a Source of Antioxidants and Anticancer Agents as Affected by Organic and Bio-organic Fertilization

    OpenAIRE

    Hanan Anwar Aly TAIE; Zeinab Abd-EL Rahman SALAMA; Radwan, Samir

    2010-01-01

    Sweet basil (Ocimum basilicum) is a popular culinary herbal crop grown for fresh or dry leaf, essential oil and seed markets. Recently, basil was shown to rank highest among species and herbal crops for phenolic compounds, essential oils which are associated with decreasing risks of cancer and aging diseases. The current study aimed to evaluate the potential activity of phenolic, flavonoids and essential oil of basil as antioxidant and anticancer activities by application organic and bio-orga...

  4. Anticancer chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1991-10-01

    This document examines chemotherapeutic agents for use in veterinary oncology. It lists some of the most common categories of chemotherapeutic drugs, such as alkylating agents and corticosteroids. For each category, the paper lists some example drugs, gives their mode of action, tumors usually susceptible to the drug, and common side effects. A brief discussion of mechanisms of drug resistance is also provided. (MHB)

  5. Local isolate of Saccharomyces cerevisiae as biocompetitive agent of Aspergillus flavus

    Directory of Open Access Journals (Sweden)

    Eni Kusumaningtyas

    2006-12-01

    Full Text Available Aspergillus flavus is a toxigenic fungus that contaminates feed and influences the animal health. Saccharomyces cerevisiae can be used as a biocompetitive agent to control the contamination. The ability of local isolate of S. cerevisiae as a biocompetitive agent for A. flavus was evaluated. A. flavus (30ml was swept on Sabouraud dextrose agar (SDA, while S. cerevisiae was swept on its left and right. Plates were incubated at 28oC for nine days. Lytic activity of S. cerevisiae was detected by pouring its suspension on the centre of the cross streaks of A. flavus. Plates were incubated at 28oC for five days. Growth inhibition of A. flavus by S. cerevisiae was determined by mixing the two fungi on Potato dextrose broth and incubated at 28oC for 24 hours. Total colony of A. flavus were then observed at incubation time of 2, 4, 6 and 24 hours by pour plates method on the SDA plates and incubated on 28oC for two days. Growth of hyphae of A. flavus sweep were inhibited with the swept of S. cerevisiae. The width of A. flavus colony treated with S. cerevisiae is narrower (3,02 cm than that of control ( 4,60 cm. The growth of A. flavus was also inhibited on the centre of cross streak where the S. cerevisiae poured. S. cerevisiae gradually reduced the colony number of A. flavus in the mixed culture of broth fungi ie. 14 x 103 CFU/ml while colony number of control is 80 x 103 CFU/ml. Results showed that S. cerevisiae could be used as biocompetitive agent of A. flavus.

  6. Microsatellite isolation and characterization for Colletotrichum spp, causal agent of anthracnose in Andean blackberry.

    Science.gov (United States)

    Marulanda, M L; López, A M; Isaza, L; López, P

    2014-01-01

    The genus Colletotrichum, comprised of pathogenic fungi that affect plants grown worldwide, causes the disease known as anthracnose in several fruit and vegetable species. Several studies conducted on plants have shown that the disease is characterized by the presence of one or several species of the fungus attacking the fruit or other organs of the same host. To develop and implement effective control strategies, it is vital to understand the genetic structure of the fungus in agricultural systems, identify associated Colletotrichum species, and define the subpopulations responsible for the disease. Molecular tools were accordingly developed to characterize genotypic populations of Colletotrichum spp, causal agent of anthracnose in commercial crops of Andean blackberry (Rubus glaucus Benth.). A microsatellite-enriched library for Colletotrichum gloeosporioides was developed to identify and characterize microsatellite loci among isolates collected in R. glaucus plantations. Thirty microsatellites were developed and tested in 36 isolates gathered from eight different blackberry-production areas of Colombia. Ten pairs of microsatellites were polymorphic. PMID:25299081

  7. Enzymatic Activity and Susceptibility to Antifungal Agents of Brazilian Environmental Isolates of Hortaea werneckii.

    Science.gov (United States)

    Formoso, Andrea; Heidrich, Daiane; Felix, Ciro Ramón; Tenório, Anne Carolyne; Leite, Belize R; Pagani, Danielle M; Ortiz-Monsalve, Santiago; Ramírez-Castrillón, Mauricio; Landell, Melissa Fontes; Scroferneker, Maria L; Valente, Patricia

    2015-12-01

    Four strains of Hortaea werneckii were isolated from different substrates in Brazil (a salt marsh macrophyte, a bromeliad and a marine zoanthid) and had their identification confirmed by sequencing of the 26S rDNA D1/D2 domain or ITS region. Most of the strains were able to express amylase, lipase, esterase, pectinase and/or cellulase, enzymes that recognize components of plant cells as substrates, but did not express albuminase, keratinase, phospholipase and DNAse, whose substrates are animal-related. Urease production was positive for all isolates, while caseinase, gelatinase and laccase production were variable among the strains. All the strains grew in media containing up to 30% NaCl. We propose that the primary substrate associated with H. werneckii is plant-related, in special in saline environments, where the fungus may live as a saprophyte and decomposer. Infection of animal-associated substrates would be secondary, with the fungus acting as an opportunistic animal pathogen. All strains were resistant to fluconazole and presented high MIC for amphotericin B, while they were susceptible to all the other antifungal agents tested. PMID:26162643

  8. Potent Anticancer Effects of Bioactive Mushroom Extracts (Phellinus linteus) on a Variety of Human Cancer Cells

    OpenAIRE

    Konno, Sensuke; Chu, Kevin; Feuer, Nicholas; Phillips, John; Choudhury, Muhammad

    2014-01-01

    Background Although several therapeutic options are currently available for patients with various cancers, the outcomes are often disappointing and a more effective modality needs to be promptly established. We have been exploring an alternative approach using natural agents and two bioactive mushroom extracts isolated from Phellinus linteus (PL), namely PL-ES and PL-I-ES, were of our interest. As anticancer effects of similar extracts have been reported in several cancers, we investigated wh...

  9. Pro-oxidant activity of dietary chemopreventive agents: an under-appreciated anti-cancer property [v1; ref status: indexed, http://f1000r.es/15s

    Directory of Open Access Journals (Sweden)

    Asfar S Azmi

    2013-06-01

    Full Text Available “Let food be thy medicine and medicine be thy food” was quoted by Hippocrates more than two thousand years ago and since ancient times the health benefits of different natural agents have been exploited. In modern research, the disease preventive benefits of many such natural agents, particularly dietary compounds and their derivatives, has been attributed to their well recognized activity as the regulators of redox state of the cell. Nevertheless, most of these studies have focused on their antioxidant activity. A large body of evidence indicates that a major fraction of these agents can elicit pro-oxidant (radical generating behavior which has been linked to their anti-cancer effects. This editorial provides an overview of the under-appreciated pro-oxidant activity of natural products, with a special focus on their ability to generate reactive oxygen species in the presence of transition metal ions, and discusses their possible use as cancer chemotherapeutic agents.

  10. Exploiting developments in nanotechnology for the preferential delivery of platinum-based anti-cancer agents to tumours: targeting some of the hallmarks of cancer.

    Science.gov (United States)

    Parker, James P; Ude, Ziga; Marmion, Celine J

    2016-01-20

    Platinum drugs as anti-cancer therapeutics are held in extremely high regard. Despite their success, there are drawbacks associated with their use; their dose-limiting toxicity, their limited activity against an array of common cancers and patient resistance to Pt-based therapeutic regimes. Current investigations in medicinal inorganic chemistry strive to offset these shortcomings through selective targeting of Pt drugs and/or the development of Pt drugs with new or multiple modes of action. A comprehensive overview showcasing how liposomes, nanocapsules, polymers, dendrimers, nanoparticles and nanotubes may be employed as vehicles to selectively deliver cytotoxic Pt payloads to tumour cells is provided. PMID:26567482

  11. Identification of potential anticancer compounds from Oplopanax horridus.

    Science.gov (United States)

    Wang, Chong-Zhi; Zhang, Zhiyu; Huang, Wei-Hua; Du, Guang-Jian; Wen, Xiao-Dong; Calway, Tyler; Yu, Chunhao; Nass, Rachael; Zhao, Jing; Du, Wei; Li, Shao-Ping; Yuan, Chun-Su

    2013-08-15

    Oplopanax horridus is a plant native to North America. Previous reports have demonstrated that this herb has antiproliferative effects on cancer cells but study mostly focused on its extract or fractions. Because there has been limited phytochemical study on this herb, its bioactive compounds are largely unknown. We recently isolated and identified 13 compounds, including six polyynes, three sesquiterpenes, two steroids, and two phenolic acids, of which five are novel compounds. In this study, we systemically evaluated the anticancer effects of compounds isolated from O. horridus. Their antiproliferative effects on a panel of human colorectal and breast cancer cells were determined using the MTS assay. Cell cycle distribution and apoptotic effects were analyzed by flow cytometry. The in vivo antitumor effect was examined using a xenograft tumor model. Among the 13 compounds, strong antiproliferative effects were observed from falcarindiol and a novel compound oplopantriol A. Falcarindiol showed the most potent antiproliferative effects, significantly inducing pro-apoptosis and cell cycle arrest in the S and G2/M phases. The anticancer potential of falcarindiol was further verified in vivo, significantly inhibiting HCT-116 tumor growth in an athymic nude mouse model at 15 mg/kg. We also analyzed the relationship between polyyne structures and their pharmacological activities. We observed that both the terminal hydroxyl group and double bond obviously affected their anticancer potential. Results from this study supplied valuable information for future semi-synthesis of polyyne derivatives to develop novel cancer chemopreventive agents. PMID:23746754

  12. Potential Activity of Basil Plants as a Source of Antioxidants and Anticancer Agents as Affected by Organic and Bio-organic Fertilization

    Directory of Open Access Journals (Sweden)

    Hanan Anwar Aly TAIE

    2010-06-01

    Full Text Available Sweet basil (Ocimum basilicum is a popular culinary herbal crop grown for fresh or dry leaf, essential oil and seed markets. Recently, basil was shown to rank highest among species and herbal crops for phenolic compounds, essential oils which are associated with decreasing risks of cancer and aging diseases. The current study aimed to evaluate the potential activity of phenolic, flavonoids and essential oil of basil as antioxidant and anticancer activities by application organic and bio-organic fertilization. A pot experiment was conducted. Basil seeds were grown, with three levels of organic fertilizers (compost in presence or absence of biofertilizer. Growth parameters, pigments content, total phenolics, total flavonoids and antioxidant activity of methanolic plant extract were examined. Application of 50% compost and 50% sand in the presence of biofertilizer resulted in enhancement fresh and dry weights, total phenolics, total flavonoids and pigment content as compared with compost alone. The constituents of essential oils extracted by hydrodistilation of basil leaves were identified by GLC. Eleven components of essential oils were identified. The highest value of antioxidant and anticancer activities were obtained in basil plants grown in 50% and 75% compost treatments in the presence of biofertilizer. These results emphasized the important of bioorganic fertilizers for enhancement the antioxidant activity of phenolics, flavonoids, and essential oils of basil plant extract.

  13. Cinnamomum verum Component 2-Methoxycinnamaldehyde: A Novel Anticancer Agent with Both Anti-Topoisomerase I and II Activities in Human Lung Adenocarcinoma A549 Cells In Vitro and In Vivo.

    Science.gov (United States)

    Wong, Ho-Yiu; Tsai, Kuen-daw; Liu, Yi-Heng; Yang, Shu-mei; Chen, Ta-Wei; Cherng, Jonathan; Chou, Kuo-Shen; Chang, Chen-Mei; Yao, Belen T; Cherng, Jaw-Ming

    2016-02-01

    Cinnamomum verum is used to make the spice cinnamon and has been used as a traditional Chinese herbal medicine. We evaluated the anticancer effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the bark of the plant, and its underlying molecular biomarkers associated with carcinogenesis in human lung adenocarcinoma A549 cells. The results show that 2-MCA suppressed proliferation and induced apoptosis as indicated by an upregulation of pro-apoptotic Bax and Bak genes and downregulation of anti-apoptotic Bcl-2 and Bcl-XL genes, mitochondrial membrane potential loss, cytochrome c release, activation of caspase-3 and -9, and morphological characteristics of apoptosis, including plasma membrane blebbing and long comet tail. In addition, 2-MCA also induced lysosomal vacuolation with increased volume of acidic compartment (VAC) and suppressions of nuclear transcription factors nuclear factor-κB (NF-κB) and both topoisomerase I and II activities. Further study reveals that the growth-inhibitory effect of 2-MCA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of 2-MCA against A549 cells is accompanied by downregulations of NF-κB binding activity and proliferative control involving apoptosis and both topoisomerase I and II activities, together with an upregulation of lysosomal vacuolation and VAC. Our data suggest that 2-MCA could be a potential agent for anticancer therapy. PMID:26676220

  14. Discovery of a novel anti-cancer agent targeting both topoisomerase I and II in hepatocellular carcinoma Hep 3B cells in vitro and in vivo: Cinnamomum verum component 2-methoxycinnamaldehyde.

    Science.gov (United States)

    Perng, Daw-Shyong; Tsai, Yu-Hsin; Cherng, Jonathan; Kuo, Chih-Wei; Shiao, Chih-Chung; Cherng, Jaw-Ming

    2016-08-01

    Cinnamomum verum has been used as a traditional Chinese herbal medicine. We evaluated the anticancer effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the bark of the plant, in hepatocellular carcinoma Hep 3B cells. The results show that 2-MCA suppressed proliferation and induced apoptosis as indicated by an up-regulation of pro-apoptotic bax and bak genes and down-regulation of anti-apoptotic bcl-2 and bcl-XL genes, mitochondrial membrane potential loss, cytochrome c release, activation of caspase 3 and 9, increase in the DNA content in sub G1, and morphological characteristics of apoptosis. 2-MCA also induced lysosomal vacuolation with increased volume of acidic compartments (VAC), suppressions of nuclear transcription factors NF-κB, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and both topoisomerase I and II activities in a dose-dependent manner. Further study reveals the growth-inhibitory effect of 2-MCA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of 2-MCA against Hep 3B cells is accompanied by downregulations of NF-κB binding activity, inflammatory responses involving COX-2 and PGE2, and proliferative control involving apoptosis, both topoisomerase I and II activities, together with an upregulation of lysosomal vacuolation and VAC. Our data suggest that 2-MCA could be a potential agent for anticancer therapy. PMID:26707867

  15. Metformin may function as anti-cancer agent via targeting cancer stem cells: the potential biological significance of tumor-associated miRNAs in breast and pancreatic cancers.

    Science.gov (United States)

    Bao, Bin; Azmi, Asfar S; Ali, Shadan; Zaiem, Feras; Sarkar, Fazlul H

    2014-06-01

    Metformin is one of the most used diabetic drugs for the management of type II diabetes mellitus (DM) in the world. Increased numbers of epidemiological and clinical studies have provided convincing evidence supporting the role of metformin in the development and progression of a variety of human tumors including breast and pancreatic cancer. Substantial pre-clinical evidence from in vitro and in vivo experimental studies strongly suggests that metformin has an anti-cancer activity mediated through the regulation of several cell signaling pathways including activation of AMP kinase (AMPK), and other direct and indirect mechanisms; however, the detailed mechanism(s) has not yet been fully understood. The concept of cancer stem cells (CSCs) has gained significant attention in recent years due its identification and defining its clinical implications in many different tumors including breast cancer and pancreatic cancer. In this review, we will discuss the protective role of metformin in the development of breast and pancreatic cancers. We will further discuss the role of metformin as an anti-cancer agent, which is in part mediated through targeting CSCs. Finally, we will discuss the potential role of metformin in the modulation of tumor-associated or CSC-associated microRNAs (miRNAs) as part of the novel mechanism of action of metformin in the development and progression of breast and pancreatic cancers. PMID:25333034

  16. Simultaneous determination of the novel thiosemicarbazone anti-cancer agent, Bp4eT, and its main phase I metabolites in plasma: application to a pilot pharmacokinetic study in rats.

    Science.gov (United States)

    Stariat, Ján; Suprunová, Vlasta; Roh, Jaroslav; Šesták, Vít; Eisner, Tomáš; Filipský, Tomáš; Mladěnka, Přemysl; Nobilis, Milan; Šimůnek, Tomáš; Klimeš, Jiří; Kalinowski, Danuta S; Richardson, Des R; Kovaříková, Petra

    2014-05-01

    Novel thiosemicarbazone metal chelators are extensively studied anti-cancer agents with marked and selective activity against a wide variety of cancer cells, as well as human tumor xenografts in mice. This study describes the first validated LC-MS/MS method for the simultaneous quantification of 2-benzoylpyridine 4-ethyl-3-thiosemicarbazone (Bp4eT) and its main metabolites (E/Z isomers of the semicarbazone structure, M1-E and M1-Z, and the amidrazone metabolite, M2) in plasma. Separation was achieved using a C18 column with ammonium formate/acetonitrile mixture as the mobile phase. Plasma samples were treated using solid-phase extraction on 96-well plates. This method was validated over the concentration range of 0.18-2.80 μM for Bp4eT, 0.02-0.37 μM for both M1-E and M1-Z, and 0.10-1.60 μM for M2. This methodology was applied to the analysis of samples from in vivo experiments, allowing for the concentration-time profile to be simultaneously assessed for the parent drug and its metabolites. The current study addresses the lack of knowledge regarding the quantitative analysis of thiosemicarbazone anti-cancer drugs and their metabolites in plasma and provides the first pharmacokinetic data on a lead compound of this class. PMID:24254882

  17. Biofilm-producing ability and efficiency of sanitizing agents against Prototheca zopfii isolates from bovine subclinical mastitis.

    Science.gov (United States)

    Gonçalves, Juliano Leonel; Lee, Sarah Hwa In; de Paula Arruda, Eurico; Pedroso Galles, Débora; Camargo Caetano, Vinícius; Fernandes de Oliveira, Carlos Augusto; Fernandes, Andrezza Maria; Veiga dos Santos, Marcos

    2015-06-01

    The objectives of the present study were to evaluate (1) the capacity of the microalga Prototheca zopfii isolated from subclinical bovine mastitis cases to form biofilms; and (2) the resistance of these isolates to sanitizing agents. Ten isolates of P. zopfii from cows with subclinical mastitis (somatic cell count>200×10(3) cells/mL), distributed in 5 dairy farms, were evaluated for their capacity to form biofilms in polystyrene microplate assays and stainless steel coupons, at 25°C and 37°C±1°C. Prototheca zopfii were isolated from milk samples via microbiological culture and analyzed by 18S rRNA gene sequencing. Biofilm formation on the coupons was observed by scanning electron microscopy. The resistance to sanitizing agents was assessed using the biofilm-forming P. zopfii isolates in stainless steel coupon assays, which were subjected to 3 sanitizers: peracetic acid, sodium hypochlorite, and iodine solution. To evaluate resistance to the sanitizers, the minimum inhibitory concentration (MIC) technique was performed using decreasing concentrations of the sanitizing agents (20, 10, 5, 2.5, 1.25, 0.625, 0.312, 0.156, 0.078, 0.039, and 0.019 g/L). After inoculating the isolates, all concentrations were evaluated at 3 distinct incubation periods (24, 48, and 72 h) to assess the effect of incubation time on the MIC. Using the polystyrene microplate assays, 1 isolate showed weak biofilm production, 5 moderate, and 4 strong, when incubated at 25°C±1. For isolates incubated at 37°C±1, 6 showed weak biofilm production and 4 moderate. All P. zopfii isolates (n=10) had the capacity to form biofilms on stainless steel coupons. The longer the incubation period of the P. zopfii isolates at different dilutions, the greater the concentrations of sanitizer needed to prevent growth of the microalgae under the tested conditions. We detected a significant effect of sanitizer and time of incubation (24, 48, and 72 h) on MIC values against P. zopfii isolates. The isolates

  18. Synthesis and in vitro evaluation of (R), (S) and (R/S)-2-hexyne-1,4-diol, a natural product produced by fungus Clitocybe catinus, and related analogs as potential anticancer agents.

    Science.gov (United States)

    Princival, Iza Mirela R G; Ferreira, Jeiely G; Silva, Teresinha G; Aguiar, Jaciana S; Princival, Jefferson L

    2016-06-15

    The search for natural products and related analogs as potential anticancer agents has seen a significant growth worldwide. Since small sized propargylic diols can be found in nature and chemically synthesized, their evaluation against cancer cells has been of great interest, being a topic of relevance to be investigated. For this purpose, a scalable approach aiming at the synthesis of several propargylic diols and their bioactivity against seven tumor cell lines were evaluated. Interestingly, when the compound 1a, a natural product produced by fungus Clitocybe catinus, was tested in its racemic mixture a more effective activity was observed if compared when enantiopure R-1a or S-1a were tested separately. PMID:27142752

  19. Native isolate of Trichoderma: a biocontrol agent with unique stress tolerance properties.

    Science.gov (United States)

    Mishra, N; Khan, S S; Sundari, S Krishna

    2016-08-01

    Species of Trichoderma are widely recognized for their biocontrol abilities, but seldom studied collectively, for their plant growth promotion, abiotic stress tolerance and bioremediation properties. Our study is a concentrated effort to establish the potential of native isolate Trichoderma harzianum KSNM (T103) to tolerate biotic (root pathogens) and abiotic stresses [high salt (100-1000 mM); heavy metal (chromium, nickel and zinc: 1-10 mM); pesticides: malathion (100-600 ppm), carbofuran (100-600 ppb)], along with its ability to support plant growth. In vitro growth promotion assays with T103 treated Vigna radiata, Vigna mungo and Hordeum vulgare confirmed 'non-species specific' growth promotion effects of T103. At lower metal concentration, T103 treatment was found to completely negate the impact of metal stress [60 % increase in radicle length (RL) with no significant decrease in %germination (%G)]. Even at 10 mM metal, T103 inoculation gave 80 % increase in %G and >50 % increase in RL. In vitro experiments confirmed high metal reduction capacity (47 %-Cr, 35 %-Ni and 42 %-Zn) of T103 at concentrations as high as 4 mM. At maximum residual concentrations of malathion (440 ppm) and carbofuran (100 ppb) reported in agricultural soils, T103 maintained 80 and 100 % survivability, respectively. T103 treatment has improved %G and RL in all three hosts challenged with pesticide. Isolate T103 was found to effectively suppress growth of three major root pathogens: Macrophomina phaseolina (65.83 %) followed by Sclerotium rolfsii (19.33 %) and Fusarium oxysporum (19.18 %). In the light of these observations, native T. harzianum (T103) seems to be a competent biocontrol agent for tropical agricultural soils contaminated with residual pesticides and heavy metals. PMID:27339311

  20. Influence of heat stress on the reactivity of isolated chicken carotid artery to vasoactive agents.

    Science.gov (United States)

    Siddegowda, Yeshavanth K Banasavadi; Leo, Marie Dennis Marcus; Kumar, Dinesh; Hooda, Om Kumar; Prakash, Vellanki Ravi; Mishra, Santosh K

    2007-11-01

    Cerebral ischaemia is considered to be an important cause of central nervous system dysfunction in heat stress. We hypothesized that heat stress would alter the reactivity of isolated carotid artery to vasoactive agents. Carotid arteries were isolated from broiler chickens maintained either at 23-24 degrees C with 55-65% humidity (control conditions) or exposed to 40 +/- 1 degrees C with 35% humidity for 4 h (heat stress). Contractions were elicited with vasoconstrictors such as 5-HT, phenylephrine, guanfacine and CaCl(2) (K(+)-depolarized) in endothelium-denuded arterial rings. Heat stress significantly increased the potency of 5-HT, but had no effect on the sensitivity of the vessel to phenylephrine or guanfacine. In contrast, it markedly decreased the potency and efficacy of CaCl(2). Vasodilator responses to ACh (endothelium-intact) and sodium nitroprusside (endothelium-denuded), however, were unaffected. Although cyclopiazonic acid (10 microm) significantly decreased 5-HT responses in both the conditions, the agonist was still more potent in heat stress. Extracellular Ca(2)(+) removal had no effect on contractions caused by 5-HT in control conditions, but it significantly decreased the agonist potency in heat stress. Interestingly, nifedipine (1 microm) markedly inhibited 5-HT-induced contractions both in control conditions and in heat stress, implying an inhibitory effect on both Ca(2)(+) influx and release. Thus, nifedipine had a markedly greater inhibitory effect on 5-HT-induced contractions in heat stress compared with control conditions. The results suggest that heat stress increased the vasoconstrictor responses to 5-HT by a mechanism that involved extracellular Ca(2)(+) influx through nifedipine-sensitive L-type calcium channels. PMID:17720746

  1. Bacterial Agents Andantibiogram of Most Common Isolated Organisms from Hands of Surgical Team Members after Scrubbing

    Directory of Open Access Journals (Sweden)

    PS Mohseni- Meybodi

    2008-04-01

    Full Text Available Introduction: Many post-surgical wound infections in hospitals cause morbidity and morality of patients and these are usually transmitted via hands of surgical personnel. The aim of the present study was to detect and antibiogram the bacterial agents following scrubbing of hands of surgical personnel before operation. Methods: Hands of 134 personnels of operation room were swabbed following scrubbing with antiseptic Betadine solution. Swab samples were inoculated on selective and differential media such as blood ager, McConky and manitol salt agar(MSA. Following incubation of media at 37c° for 24hr, bacterial species were identified using differential related tests. The isolated species were than antibiogramed and the results together with other data was analysed by SPSS software program. Results: Of the total of 134 cases, 81(60.4% were male and 53(39.6% female. The mean scrub time for each person was (206.1+/-103.2 seconds; 6 to 60 seconds base change. Increasing time of scrub was significantly correlated with decreasing rate of bacteria (P=0.003, (R=-0.254. Contamination was present in 129(96.3% cases following scrubbing. Maximum contamination was observed in nails (92.5%. Average number of bacteria for each individual was between 0 and 159. 62.6% of isolated bacteria were non- staphylococci and 7.7% were S. aureus. Vancomycin and ceftizoxim were the most sensitive, while penicillin was the least sensitive antibiotic. Conclusion: Results revealed that hand contamination was more than the expected standard level. Therefore, regarding the critical task of surgical personnel, training of all operation room staff is highly recommended to minimize the rate of contamination.

  2. Efficacy of a non-hypercalcemic vitamin-D2 derived anti-cancer agent (MT19c and inhibition of fatty acid synthesis in an ovarian cancer xenograft model.

    Directory of Open Access Journals (Sweden)

    Richard G Moore

    Full Text Available BACKGROUND: Numerous vitamin-D analogs exhibited poor response rates, high systemic toxicities and hypercalcemia in human trials to treat cancer. We identified the first non-hypercalcemic anti-cancer vitamin D analog MT19c by altering the A-ring of ergocalciferol. This study describes the therapeutic efficacy and mechanism of action of MT19c in both in vitro and in vivo models. METHODOLOGY/PRINCIPAL FINDING: Antitumor efficacy of MT19c was evaluated in ovarian cancer cell (SKOV-3 xenografts in nude mice and a syngenic rat ovarian cancer model. Serum calcium levels of MT19c or calcitriol treated animals were measured. In-silico molecular docking simulation and a cell based VDR reporter assay revealed MT19c-VDR interaction. Genomewide mRNA analysis of MT19c treated tumors identified drug targets which were verified by immunoblotting and microscopy. Quantification of cellular malonyl CoA was carried out by HPLC-MS. A binding study with PPAR-Y receptor was performed. MT19c reduced ovarian cancer growth in xenograft and syngeneic animal models without causing hypercalcemia or acute toxicity. MT19c is a weak vitamin-D receptor (VDR antagonist that disrupted the interaction between VDR and coactivator SRC2-3. Genome-wide mRNA analysis and western blot and microscopy of MT19c treated xenograft tumors showed inhibition of fatty acid synthase (FASN activity. MT19c reduced cellular levels of malonyl CoA in SKOV-3 cells and inhibited EGFR/phosphoinositol-3kinase (PI-3K activity independently of PPAR-gamma protein. SIGNIFICANCE: Antitumor effects of non-hypercalcemic agent MT19c provide a new approach to the design of vitamin-D based anticancer molecules and a rationale for developing MT19c as a therapeutic agent for malignant ovarian tumors by targeting oncogenic de novo lipogenesis.

  3. Design and synthesis of novel 5,6-disubstituted pyridine-2,3-dione-3-thiosemicarbazone derivatives as potential anticancer agents.

    Science.gov (United States)

    Xie, Wenlin; Xie, Shimin; Zhou, Ying; Tang, Xufu; Liu, Jian; Yang, Wenqian; Qiu, Minghua

    2014-06-23

    A series of 5,6-disubstituted pyridine-2,3-dione-3-thiosemicarbazone derivatives(2a-2n) and 5,6-disubstituted pyridine-2,3-dione S-benzyl-3-thiosemicarbazones(3a-3g) were synthesized starting from 2,3-dihydroxypyridine via oxidation-Michael additions, condensations and nucleophilic substitutions. The structures of the compounds were established by IR, (1)H NMR, (13)C NMR, and HRMS. All newly synthesized compounds were screened for their anticancer activity against Breast cancer (MCF-7), Colon cancer (HCT-116) and hepatocellular cancer (BEL7402) cell lines. Bioassay results indicated that most of the prepared compounds exhibited cytotoxicity against various cancer cells in vitro. Some of the compounds exhibited promising antiproliferative activity, which were comparable to the positive control (5-fluorouracil). The structure-activity relationship was discussed. PMID:24819956

  4. Synthesis of novel triazole/isoxazole functionalized 7-(trifluoromethyl)pyrido[2,3-d]pyrimidine derivatives as promising anticancer and antibacterial agents.

    Science.gov (United States)

    Naresh Kumar, R; Jitender Dev, G; Ravikumar, N; Krishna Swaroop, D; Debanjan, B; Bharath, G; Narsaiah, B; Nishant Jain, S; Gangagni Rao, A

    2016-06-15

    A series of novel 1,2,3-triazole/isoxazole functionalized pyrido[2,3-d]pyrimidine derivatives 6a-c, 7a-h and 8a-e were prepared in series of synthetic steps. All the compounds screened for the anticancer activity against four human cancer cell lines using Nocodazole as standard. Compounds 7d and 7h showed highest activity against PANC-1 (pancreatic cancer) and A549 (lung cancer) cell lines respectively and more than standard. All the compounds also screened for antibacterial activity using Rifampicin and Ciprofloxacin as standards and identified promising compounds further evaluated for minimum inhibitory concentration to validate the data. PMID:27130357

  5. Novel Marine Compounds: Anticancer or Genotoxic?

    Directory of Open Access Journals (Sweden)

    Arif Jamal M.

    2004-01-01

    Full Text Available In the past several decades, marine organisms have generously gifted to the pharmaceutical industries numerous naturally bioactive compounds with antiviral, antibacterial, antimalarial, anti-inflammatory, antioxidant, and anticancer potentials. But till date only few anticancer drugs (cytarabine, vidarabine have been commercially developed from marine compounds while several others are currently in different clinical trials. Majority of these compounds were tested in the tumor xenograft models, however, lack of anticancer potential data in the chemical- and/or oncogene-induced pre-initiation animal carcinogenesis models might have cost some of the marine anticancer compounds an early exit from the clinical trials. This review critically discusses importance of preclinical evaluation, failure of human clinical trials with certain potential anticancer agents, the screening tests used, and choice of biomarkers.

  6. Screening of Pseudomonas sp. Isolated from Rhizosphere of Soybean Plant as Plant Growth Promoter and Biocontrol Agent

    Directory of Open Access Journals (Sweden)

    Aris T. Wahyudi

    2011-01-01

    Full Text Available Problem statement: Pseudomonas spesies are one of the rihizobacterial group that have an important role in plant growth promoter and plant health. To prepare them as inoculants, they must have a range of characters as growth promoter such as Indole Acetic Acid (IAA producers which can promote the growth of plants and solubilize phosphates. In addition, they must also have the various characters that act as biocontrol agents such as siderofor, chitinase and anti-fungal compound producers. Approach: Pseudomonas sp isolated from soybeans rhizospere and identified based on physiological reactions and 16S rRNA gene sequences. Various tests for the determination of the growth promoter were based on IAA production, phosphate solubilization and growth promoter of length of root and stems and number of lateral roots of soybean sprouts. Test of siderophore, chitinase, as well as anti anti-fungal compounds productions to inhibit the growth of Fusarium oxysporum, Rhizoctonia solani and Sclerotium rolfsii, were used as a biocontrol agent determination. Hypersensitivity test was used to screen for Pseudomonas sp classified as non-pathogenic rhizobacteria. Results: Fourteen isolates identified as a non-pathogenic Pseudomonas sp that produced IAA and Promoted enhancement of root length, shoot length, or number of lateral root. Among those 14 isolates, 8 isolates showed phosphate solubilizing activity, 12 isolates capable of producing siderophore and six isolates were observed to have chitinolytic activity. Only three isolates were able to inhibit the growth of Fusarium oxysporum in high level. While one and two isolates inhibited Sclerotium rolfsii and Rhizoctonia solani in high level, respectively. Conclusion: On the basis of excellent growth promoter and biocontrol activities, we recommended 5 isolates of Pseudomonas sp which were Crb-3, Crb-16, Crb-17, Crb-44 and Crb-94 as potential isolates of Pseudomonas sp that could be applied as

  7. Bio-synthesis of silver nanoparticles using Potentilla fulgens Wall. ex Hook. and its therapeutic evaluation as anticancer and antimicrobial agent

    International Nuclear Information System (INIS)

    The present study aims to develop an easy and eco-friendly method for the synthesis of silver nanoparticles using extracts from the medicinal plant, Potentilla fulgens and evaluation of its anticancer and antimicrobial properties. The various parts of P. fulgens were screened and the root extract was found to have the highest potential for the synthesis of nanoparticles. The root extracts were able to quickly reduce Ag+ to Ag0 and stabilized the nanoparticles. The synthesis of nanoparticles was confirmed by UV–Visible spectrophotometry and further characterized using Zeta sizer, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscope (TEM) and X-ray diffraction (XRD). Electron microscopic study showed that the size of the nanoparticle was in the range of 10 to 15 nm and spherical in shape. The studies of phytochemical analysis of nanoparticles indicated that the adsorbed components on the surface of nanoparticles were mainly flavonoid in nature. Furthermore, nanoparticles were evaluated as cytotoxic against various cancer cell lines and 0.2 to 12 μg/mL nanoparticles showed good toxicity. The IC50 value of nanoparticles was found to be 4.91 and 8.23 μg/mL against MCF-7 and U-87 cell lines, respectively. Additionally, the apoptotic effect of synthesized nanoparticles on normal and cancer cells was studied using trypan blue assay and flow-cytometric analysis. The results indicate the synthesized nanoparticle ability to kill cancer cells compared to normal cells. The nanoparticles also exhibited comparable antimicrobial activity against both Gram-positive and Gram-negative bacteria. - Highlights: • Bio-synthesis of AgNPs using a medicinal plant Potentilla fulgens Wall. ex Hook. • Optimization of NP synthesis and its characterization using various techniques • Determination of therapeutic potential in terms of anticancer and antimicrobial properties • To know the mechanistic apoptosis effect of AgNPs

  8. Bio-synthesis of silver nanoparticles using Potentilla fulgens Wall. ex Hook. and its therapeutic evaluation as anticancer and antimicrobial agent

    Energy Technology Data Exchange (ETDEWEB)

    Mittal, Amit Kumar [Department of Pharmaceutical Technology Biotechnology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, 160062 Punjab (India); Tripathy, Debabrata [Department of Biotechnology and Bioinformatics, North Eastern Hill University, Shillong, 793002 Meghalaya (India); Choudhary, Alka [Department of Natural Products, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, 160062 Punjab (India); Aili, Pavan Kumar [Department of Pharmaceutical Technology Biotechnology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, 160062 Punjab (India); Chatterjee, Anupam [Department of Biotechnology and Bioinformatics, North Eastern Hill University, Shillong, 793002 Meghalaya (India); Singh, Inder Pal [Department of Natural Products, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, 160062 Punjab (India); Banerjee, Uttam Chand, E-mail: ucbanerjee@niper.ac.in [Department of Pharmaceutical Technology Biotechnology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, 160062 Punjab (India)

    2015-08-01

    The present study aims to develop an easy and eco-friendly method for the synthesis of silver nanoparticles using extracts from the medicinal plant, Potentilla fulgens and evaluation of its anticancer and antimicrobial properties. The various parts of P. fulgens were screened and the root extract was found to have the highest potential for the synthesis of nanoparticles. The root extracts were able to quickly reduce Ag{sup +} to Ag{sup 0} and stabilized the nanoparticles. The synthesis of nanoparticles was confirmed by UV–Visible spectrophotometry and further characterized using Zeta sizer, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscope (TEM) and X-ray diffraction (XRD). Electron microscopic study showed that the size of the nanoparticle was in the range of 10 to 15 nm and spherical in shape. The studies of phytochemical analysis of nanoparticles indicated that the adsorbed components on the surface of nanoparticles were mainly flavonoid in nature. Furthermore, nanoparticles were evaluated as cytotoxic against various cancer cell lines and 0.2 to 12 μg/mL nanoparticles showed good toxicity. The IC{sub 50} value of nanoparticles was found to be 4.91 and 8.23 μg/mL against MCF-7 and U-87 cell lines, respectively. Additionally, the apoptotic effect of synthesized nanoparticles on normal and cancer cells was studied using trypan blue assay and flow-cytometric analysis. The results indicate the synthesized nanoparticle ability to kill cancer cells compared to normal cells. The nanoparticles also exhibited comparable antimicrobial activity against both Gram-positive and Gram-negative bacteria. - Highlights: • Bio-synthesis of AgNPs using a medicinal plant Potentilla fulgens Wall. ex Hook. • Optimization of NP synthesis and its characterization using various techniques • Determination of therapeutic potential in terms of anticancer and antimicrobial properties • To know the mechanistic

  9. Synthesis, characterization of some novel 1,3,4-oxadiazole compounds containing 8-hydroxy quinolone moiety as potential antibacterial and anticancer agents

    Directory of Open Access Journals (Sweden)

    Vinayak Mahadev Adimule

    2014-12-01

    Full Text Available In the present work a series of novel derivatives of 8-hydroxy quinolone substituted 1,3,4-oxadiazole compounds were synthesized by convergent synthetic method and studied for their antibacterial and anticancer properties. The cell lines used for cytotoxic evaluation were HeLa, Caco-2 and MCF7. The synthetic chemistry involved conversion of various substituted aromatic acids into ethyl ester 2a-e. The ethyl ester was converted into corresponding carbohydrazide 3a-e. Carbohydrazides are reacted with chloroacetic acid, phosphorous oxytrichloride and irradiated with microwave in order to obtain the various key intermediates 2-(chloromethyl-5-(substituted phenyl-1,3,4-oxadiazole 4a-e. The 2-(chloromethyl-5-(substituted phenyl-1,3,4-oxadiazole was reacted with 8-hydroxy quinolone in presence of sodium hydride and obtained a series of 8-hydroxy quinoline substituted 1,3,4-oxadiazoles 5a-e. Among the synthesised compounds, the cytotoxicity of the compound 5b i.e. 8-{[5-(2,4-dichlorophenyl-1,3,4-oxadiazol-2-yl]methoxy}quinoline against MCF7 with IC50 of 5.3µM and the compound 5e i.e. 8-{[5-(4-bromophenyl-1,3,4-oxadiazol-2-yl]methoxy}quinoline showed MIC of < 6.25µg/mL against Staphylococcus aureus which is comparable with the known standards. The standards used for cytotoxic evaluation was 5-fluorouracil and for antibacterial was nitrofurazone

  10. Preparation of thermo and pH-responsive polymer@Au/Fe3O4 core/shell nanoparticles as a carrier for delivery of anticancer agent

    International Nuclear Information System (INIS)

    In this work, a thermo and pH-responsive poly-N-isopropylacrylamide-co-itaconic acid containing thiol side groups were successfully synthesized to prepare Doxorubicin-loaded polymer@Au/Fe3O4 core/shell nanoparticles (DOX-NPs). Copolymer and NPs were fully characterized by FT-IR, HNMR, photo-correlation spectroscopy, SEM, X-ray diffraction, vibrating-sample magnetometer, thermal gravimetric analysis, and UV–Vis spectroscopy. The stimuli-responsive characteristics of NPs were evaluated by in vitro release study in simulated cancerous environment. The biocompatibility and cytotoxic properties of NPs and DOX-NPs are explored by MTT method. The prepared NPs with the size of 50 nm showed paramagnetic characteristics with suitable and stable dispersion at physiological medium and high loading capacity (up to 55 %) of DOX. DOX-NPs yielded a pH- and temperature-triggered release of entrapped drugs at tumor tissue environment (59 % of DOX release) compared to physiological condition (20 % of DOX release) during 48 h. In vitro cytotoxicity studies indicated that the NPs showed no cytotoxicity on A549 cells at different amounts after incubation for 72 h confirming its suitability as a drug carrier. DOX-NPs, on the other hand, caused an efficient anticancer performance as verified by MTT assay test. It was concluded that developed NPs by us in this study may open the possibilities for targeted delivery of DOX to the cancerous tissues

  11. Synthesis and characterization of mixed-ligand diimine-piperonal thiosemicarbazone complexes of ruthenium(II): Biophysical investigations and biological evaluation as anticancer and antibacterial agents

    Science.gov (United States)

    Beckford, Floyd A.; Thessing, Jeffrey; Shaloski, Michael, Jr.; Canisius Mbarushimana, P.; Brock, Alyssa; Didion, Jacob; Woods, Jason; Gonzalez-Sarrías, Antonio; Seeram, Navindra P.

    2011-04-01

    We have used a novel microwave-assisted method developed in our laboratories to synthesize a series of ruthenium-thiosemicarbazone complexes. The new thiosemicarbazone ligands are derived from benzo[ d][1,3]dioxole-5-carbaldehyde (piperonal) and the complexes are formulated as [(diimine) 2Ru(TSC)](PF 6) 2 (where the TSC is the bidentate thiosemicarbazone ligand). The diimine in the complexes is either 2,2'-bipyridine or 1,10-phenanthroline. The complexes have been characterized by spectroscopic means (NMR, IR and UV-Vis) as well as by elemental analysis. We have studied the biophysical characteristics of the complexes by investigating their anti-oxidant ability as well as their ability to disrupt the function of the human topoisomerase II enzyme. The complexes are moderately strong binders of DNA with binding constants of 10 4 M -1. They are also strong binders of human serum albumin having binding constants on the order of 10 4 M -1. The complexes show good in vitro anticancer activity against human colon cancer cells, Caco-2 and HCT-116 and indeed show some cytotoxic selectivity for cancer cells. The IC 50 values range from 7 to 159 μM (after 72 h drug incubation). They also have antibacterial activity against Gram-positive strains of pathogenic bacteria with IC 50 values as low as 10 μM; little activity was seen against Gram-negative strains. It has been established that all the compounds are catalytic inhibitors of human topoisomerase II.

  12. Design, synthesis and molecular modeling studies of few chalcone analogues of benzimidazole for epidermal growth factor receptor inhibitor in search of useful anticancer agent.

    Science.gov (United States)

    Chhajed, Santosh S; Sonawane, Sandeep S; Upasani, Chandrashekhar D; Kshirsagar, Sanjay J; Gupta, Pramodkumar P

    2016-04-01

    In the present investigation, few 3-(substitutedphenyl)-1-[2-(1-hydroxy-ethyl)]-1H-benzimidazol-1-yl)prop-2-en-1-ones are EGFR antagonist are designed, by molecular docking analysis. The synthesized compounds were tested for their in vitro anticancer activity by propidium iodide fluorescent assay and Trypan blue viability assay against colorectal cancer cell lines (HCT116) and non-small cell lung cancer cell lines (H460). Human Epithelial Kidney cell lines (HEK) are used as normal cell lines for studying effect of drug on non-cancerous cells within human body. Evaluation of cytotoxic studies of synthesized compounds CHL(1-8) reveal that compound CHL1 [IC50=7.31 and 10.16 μM against HCT116 and H460 cell lines respectively, by PI assay] and CHL8 [IC50=12.52 and 6.83 against HCT116 and H460μM cell lines respectively] possess promising cytotoxic activity. PMID:26878127

  13. Design and synthesis of C3-pyrazole/chalcone-linked beta-carboline hybrids: antitopoisomerase I, DNA-interactive, and apoptosis-inducing anticancer agents.

    Science.gov (United States)

    Kamal, Ahmed; Srinivasulu, Vunnam; Nayak, V Lakshma; Sathish, Manda; Shankaraiah, Nagula; Bagul, Chandrakant; Reddy, N V Subba; Rangaraj, Nandini; Nagesh, Narayana

    2014-09-01

    A series of β-carboline hybrids bearing a substituted phenyl and a chalcone/(N-acetyl)-pyrazole moiety at the C1 and C3 positions, respectively, was designed, synthesized, and evaluated for anticancer activity. These new hybrid molecules showed significant cytotoxic activity, with IC50 values ranging from indol-3-yl)prop-2-en-1-one (7 d) and 1-(3-(furan-2-yl)-5-(1-(4-(trifluoromethyl)phenyl)-9H-pyrido[3,4-b]indol-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (8 d) could effectively cleave pBR322 plasmid DNA upon irradiation with UV light. Active hybrid 8 d inhibited DNA topoisomerase I activity efficiently and preserved DNA in the supercoiled form. To further corroborate the biological activities, as well as to understand the nature of the interaction of these hybrids with DNA, spectroscopic studies were also performed. Unlike simple β-carboline alkaloids, the binding mode of these new hybrid molecules with DNA was not similar, and both biophysical as well as molecular docking studies speculated a combilexin-type of interaction with DNA. Further, an in silico study of these β-carboline hybrids revealed their drug-like properties. PMID:24470122

  14. Study on the thermodynamics of the binding of iminium and alkanolamine forms of the anticancer agent sanguinarine to human serum albumin

    International Nuclear Information System (INIS)

    Highlights: ► Energetics of sanguinarine–human serum albumin has been elucidated. ► The alkanolamine binds stronger than iminium. ► Enthalpy driven binding for iminium was revealed. ► Alkanolamine form binding was favored by negative enthalpy and entropy changes. ► Spectroscopic results support calorimetry data. - Abstract: Sanguinarine is an anticancer plant alkaloid that can exist in the charged iminium and neutral alkanolamine forms. The thermodynamics of the interaction of the two forms with human serum albumin was investigated using calorimetric techniques, and the data supplemented with circular dichroism and spectrofluorimetric studies. The thermodynamic results show that there is only one class of binding for sanguinarine on HSA. The equilibrium constant was four times higher for the alkanolamine (Ka = 2.18 · 105 M−1) than for iminium (Ka = 5.97 · 104 M−1). The binding was enthalpy driven for iminium and favoured by both a negative enthalpy and a stronger favourable entropy contribution for the alkanolamine. Temperature dependent calorimetric data yielded values of ΔCp∘ that are consistent with the involvement of different molecular forces in the complexation of the two forms of sanguinarine to HSA. The fluorescence quenching data suggest a static quenching mechanism. Synchronous fluorescence and circular dichroic data are consistent with a conformational change in the protein on binding that was also higher for the alkanolamine form.

  15. Isolation, identification, and characterization of novel arenaviruses, the etiological agents of boid inclusion body disease.

    Science.gov (United States)

    Hetzel, Udo; Sironen, Tarja; Laurinmäki, Pasi; Liljeroos, Lassi; Patjas, Aino; Henttonen, Heikki; Vaheri, Antti; Artelt, Annette; Kipar, Anja; Butcher, Sarah J; Vapalahti, Olli; Hepojoki, Jussi

    2013-10-01

    Boid inclusion body disease (BIBD) is a progressive, usually fatal disease of constrictor snakes, characterized by cytoplasmic inclusion bodies (IB) in a wide range of cell types. To identify the causative agent of the disease, we established cell cultures from BIBD-positive and -negative boa constrictors. The IB phenotype was maintained in cultured cells of affected animals, and supernatants from these cultures caused the phenotype in cultures originating from BIBD-negative snakes. Viruses were purified from the supernatants by ultracentrifugation and subsequently identified as arenaviruses. Purified virus also induced the IB phenotype in naive cells, which fulfilled Koch's postulates in vitro. One isolate, tentatively designated University of Helsinki virus (UHV), was studied in depth. Sequencing confirmed that UHV is a novel arenavirus species that is distinct from other known arenaviruses including those recently identified in snakes with BIBD. The morphology of UHV was established by cryoelectron tomography and subtomographic averaging, revealing the trimeric arenavirus spike structure at 3.2-nm resolution. Immunofluorescence, immunohistochemistry, and immunoblotting with a polyclonal rabbit antiserum against UHV and reverse transcription-PCR (RT-PCR) revealed the presence of genetically diverse arenaviruses in a large cohort of snakes with BIBD, confirming the causative role of arenaviruses. Some snakes were also found to carry arenavirus antibodies. Furthermore, mammalian cells (Vero E6) were productively infected with UHV, demonstrating the potential of arenaviruses to cross species barriers. In conclusion, we propose the newly identified lineage of arenaviruses associated with BIBD as a novel taxonomic entity, boid inclusion body disease-associated arenaviruses (BIBDAV), in the family Arenaviridae. PMID:23926354

  16. Discovery of a novel anticancer agent with both anti-topoisomerase I and II activities in hepatocellular carcinoma SK-Hep-1 cells in vitro and in vivo: Cinnamomum verum component 2-methoxycinnamaldehyde

    Directory of Open Access Journals (Sweden)

    Perng DS

    2016-01-01

    proliferative control involving apoptosis, both topoisomerase I and II activities, together with an upregulation of lysosomal vacuolation and volume of acidic compartments. Similar effects (including all of the above-mentioned effects were found in other tested cell lines, including human hepatocellular carcinoma Hep 3B, lung adenocarcinoma A549, squamous cell carcinoma NCI-H520, colorectal adenocarcinoma COLO 205, and T-lymphoblastic MOLT-3 (results not shown. Our data ­suggest that 2-MCA could be a potential agent for anticancer therapy. Keywords: 2-methoxycinnamaldehyde, anticancer, SK-Hep-1 cells, topoisomerase I, topoisomerase II

  17. Discovery of a novel anticancer agent with both anti-topoisomerase I and II activities in hepatocellular carcinoma SK-Hep-1 cells in vitro and in vivo: Cinnamomum verum component 2-methoxycinnamaldehyde.

    Science.gov (United States)

    Perng, Daw-Shyong; Tsai, Yu-Hsin; Cherng, Jonathan; Wang, Jeng-Shing; Chou, Kuo-Shen; Shih, Chia-Wen; Cherng, Jaw-Ming

    2016-01-01

    Cinnamomum verum is used to make the spice cinnamon and has been used as a traditional Chinese herbal medicine for various applications. We evaluated the anticancer effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the bark of the plant, and its underlying molecular biomarkers associated with carcinogenesis in human hepatocellular carcinoma SK-Hep-1 cell line. The results show that 2-MCA suppressed proliferation and induced apoptosis as indicated by mitochondrial membrane potential loss, activation of caspase-3 and caspase-9, increase in the DNA content in sub-G1, and morphological characteristics of apoptosis, including blebbing of plasma membrane, nuclear condensation, fragmentation, apoptotic body formation, and long comet tail. In addition, 2-MCA also induced lysosomal vacuolation with increased volume of acidic compartments, suppressions of nuclear transcription factors NF-κB, cyclooxygenase-2, prostaglandin E2 (PGE2), and both topoisomerase I and II activities in a dose-dependent manner. Further study reveals the growth-inhibitory effect of 2-MCA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of 2-MCA against SK-Hep-1 cells is accompanied by downregulations of NF-κB-binding activity, inflammatory responses involving cyclooxygenase-2 and PGE2, and proliferative control involving apoptosis, both topoisomerase I and II activities, together with an upregulation of lysosomal vacuolation and volume of acidic compartments. Similar effects (including all of the above-mentioned effects) were found in other tested cell lines, including human hepatocellular carcinoma Hep 3B, lung adenocarcinoma A549, squamous cell carcinoma NCI-H520, colorectal adenocarcinoma COLO 205, and T-lymphoblastic MOLT-3 (results not shown). Our data suggest that 2-MCA could be a potential agent for anticancer therapy. PMID:26792981

  18. Isolation, screening, and characterization of surface-active agent-producing, oil-degrading marine bacteria of Mumbai Harbor.

    Science.gov (United States)

    Mohanram, Rajamani; Jagtap, Chandrakant; Kumar, Pradeep

    2016-04-15

    Diverse marine bacterial species predominantly found in oil-polluted seawater produce diverse surface-active agents. Surface-active agents produced by bacteria are classified into two groups based on their molecular weights, namely biosurfactants and bioemulsifiers. In this study, surface-active agent-producing, oil-degrading marine bacteria were isolated using a modified Bushnell-Haas medium with high-speed diesel as a carbon source from three oil-polluted sites of Mumbai Harbor. Surface-active agent-producing bacterial strains were screened using nine widely used methods. The nineteen bacterial strains showed positive results for more than four surface-active agent screening methods; further, these strains were characterized using biochemical and nucleic acid sequencing methods. Based on the results, the organisms belonged to the genera Acinetobacter, Alcanivorax, Bacillus, Comamonas, Chryseomicrobium, Halomonas, Marinobacter, Nesterenkonia, Pseudomonas, and Serratia. The present study confirmed the prevalence of surface-active agent-producing bacteria in the oil-polluted waters of Mumbai Harbor. PMID:26912197

  19. Drug delivery system for an anticancer agent, chlorogenate-Zn/Al-layered double hydroxide nanohybrid synthesised using direct co-precipitation and ion exchange methods

    Science.gov (United States)

    Barahuie, Farahnaz; Hussein, Mohd Zobir; Arulselvan, Palanisamy; Fakurazi, Sharida; Zainal, Zulkarnain

    2014-09-01

    A nano-structured drug-inorganic clay hybrid involving an active anticancer compound, which is chlorogenic acid (CA) intercalated into Zn/Al-layered double hydroxide, has been assembled via ion-exchange and co-precipitation methods to form a nanohybrid CZAE (a chlorogenic acid-Zn/Al nanohybrid synthesised using an ion-exchange method) and CZAC (a chlorogenic acid-Zn/Al nanohybrid synthesised using a direct method), respectively. The X-ray diffraction (XRD) results confirmed that the CA-LDH had a hybrid structure in which the anionic chlorogenate is arranged between the interlayers as a horizontal monolayer at 90 and 20° angles from the x axis for CZAE and CZAC, respectively. Both nanohybrids have the properties of mesoporous materials. The high loading percentage of chlorogenic acid (approximately 43.2% for CZAE and 45.3% for CZAC) with basal spacings of 11.7 and 12.6 Å for CZAE and CZAC, respectively, corroborates the successful intercalation of chlorogenic acid into the interlayer gallery of layered double hydroxides. Free chlorogenic acid and the synthesised nanocomposites (CZAE, CZAC) were assessed for their cytotoxicity against various cancer cells. The Fourier transform infrared data supported the formation of both nanohybrids, and a thermal analysis showed that the nanohybrids are more thermally stable than their counterparts. The chlorogenate shows a sustained release, and the release rate of chlorogenate from CZAE and CZAC nanohybrids at pH 7.4 is remarkably lower than that at pH 4.8 due to their different release mechanisms. The release rate of chlorogenate from both nanohybrids can be described as pseudo-second order. The present investigation revealed the potential of the nanohybrids to enhance the in vitro anti-tumour effect of chlorogenic acid in liver and lung cancer cells in vitro.

  20. Bio-synthesis of silver nanoparticles using Potentilla fulgens Wall. ex Hook. and its therapeutic evaluation as anticancer and antimicrobial agent.

    Science.gov (United States)

    Mittal, Amit Kumar; Tripathy, Debabrata; Choudhary, Alka; Aili, Pavan Kumar; Chatterjee, Anupam; Singh, Inder Pal; Banerjee, Uttam Chand

    2015-08-01

    The present study aims to develop an easy and eco-friendly method for the synthesis of silver nanoparticles using extracts from the medicinal plant, Potentilla fulgens and evaluation of its anticancer and antimicrobial properties. The various parts of P. fulgens were screened and the root extract was found to have the highest potential for the synthesis of nanoparticles. The root extracts were able to quickly reduce Ag(+) to Ag(0) and stabilized the nanoparticles. The synthesis of nanoparticles was confirmed by UV-Visible spectrophotometry and further characterized using Zeta sizer, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscope (TEM) and X-ray diffraction (XRD). Electron microscopic study showed that the size of the nanoparticle was in the range of 10 to 15 nm and spherical in shape. The studies of phytochemical analysis of nanoparticles indicated that the adsorbed components on the surface of nanoparticles were mainly flavonoid in nature. Furthermore, nanoparticles were evaluated as cytotoxic against various cancer cell lines and 0.2 to 12 μg/mL nanoparticles showed good toxicity. The IC50 value of nanoparticles was found to be 4.91 and 8.23 μg/mL against MCF-7 and U-87 cell lines, respectively. Additionally, the apoptotic effect of synthesized nanoparticles on normal and cancer cells was studied using trypan blue assay and flow-cytometric analysis. The results indicate the synthesized nanoparticle ability to kill cancer cells compared to normal cells. The nanoparticles also exhibited comparable antimicrobial activity against both Gram-positive and Gram-negative bacteria. PMID:26042698

  1. Isolation and identification of Avibacterium paragallinarum, the causal agent of infectious coryza (IC) from layer chickens in Bangladesh

    OpenAIRE

    Akter, S.; Ali, M.; Das, P.M; Hossain, M. M.

    2013-01-01

    This study was carried out for the isolation and identification of Avibacterium paragallinarum, the etiological agent of infectious coryza (IC). Pathological changes were also investigated that occurred in organs in layer chickens obtained from some selected areas of Bangladesh. A nasal swabs (n=30) from dead chickens and four swabs from live chickens were collected aseptically. The organisms from swabs were cultured in different media, stained, and followed by sugar fermentation and biochemi...

  2. In Vitro Activities of 15 Antimicrobial Agents against 110 Toxigenic Clostridium difficile Clinical Isolates Collected from 1983 to 2004▿

    OpenAIRE

    Hecht, David W.; Galang, Minerva A.; Sambol, Susan P.; Osmolski, James R.; Johnson, Stuart; Gerding, Dale N

    2007-01-01

    The incidence and severity of Clostridium difficile-associated disease (CDAD) is increasing, and standard treatment is not always effective. Therefore, more-effective antimicrobial agents and treatment strategies are needed. We used the agar dilution method to determine the in vitro susceptibility of the following antimicrobials against 110 toxigenic clinical isolates of C. difficile from 1983 to 2004, primarily from the United States: doripenem, meropenem, gatifloxacin, levofloxacin, moxiflo...

  3. Reduced Susceptibility to Rifampicin and Resistance to Multiple Antimicrobial Agents among Brucella abortus Isolates from Cattle in Brazil

    OpenAIRE

    Barbosa Pauletti, Rebeca; Reinato Stynen, Ana Paula; Pinto da Silva Mol, Juliana; Seles Dorneles, Elaine Maria; Alves, Telma Maria; de Sousa Moura Souto, Monalisa; Minharro, Silvia; Heinemann, Marcos Bryan; Lage, Andrey Pereira

    2015-01-01

    This study aimed to determine the susceptibility profile of Brazilian Brucella abortus isolates from cattle to eight antimicrobial agents that are recommended for the treatment of human brucellosis and to correlate the susceptibility patterns with origin, biotype and MLVA16-genotype of the strains. Screening of 147 B. abortus strains showed 100% sensitivity to doxycycline and ofloxacin, one (0.68%) strain resistant to ciprofloxacin, two strains (1.36%) resistant to streptomycin, two strains (...

  4. Drug delivery system for an anticancer agent, chlorogenate-Zn/Al-layered double hydroxide nanohybrid synthesised using direct co-precipitation and ion exchange methods

    Energy Technology Data Exchange (ETDEWEB)

    Barahuie, Farahnaz [Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia, 43400 UPM Serdang, Selangor (Malaysia); Hussein, Mohd Zobir, E-mail: mzobir@putra.upm.edu.my [Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia, 43400 UPM Serdang, Selangor (Malaysia); Arulselvan, Palanisamy [Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor (Malaysia); Fakurazi, Sharida [Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor (Malaysia); Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor (Malaysia); Zainal, Zulkarnain [Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia, 43400 UPM Serdang, Selangor (Malaysia)

    2014-09-15

    A nano-structured drug-inorganic clay hybrid involving an active anticancer compound, which is chlorogenic acid (CA) intercalated into Zn/Al-layered double hydroxide, has been assembled via ion-exchange and co-precipitation methods to form a nanohybrid CZAE (a chlorogenic acid-Zn/Al nanohybrid synthesised using an ion-exchange method) and CZAC (a chlorogenic acid-Zn/Al nanohybrid synthesised using a direct method), respectively. The X-ray diffraction (XRD) results confirmed that the CA-LDH had a hybrid structure in which the anionic chlorogenate is arranged between the interlayers as a horizontal monolayer at 90 and 20° angles from the x axis for CZAE and CZAC, respectively. Both nanohybrids have the properties of mesoporous materials. The high loading percentage of chlorogenic acid (approximately 43.2% for CZAE and 45.3% for CZAC) with basal spacings of 11.7 and 12.6 Å for CZAE and CZAC, respectively, corroborates the successful intercalation of chlorogenic acid into the interlayer gallery of layered double hydroxides. Free chlorogenic acid and the synthesised nanocomposites (CZAE, CZAC) were assessed for their cytotoxicity against various cancer cells. The Fourier transform infrared data supported the formation of both nanohybrids, and a thermal analysis showed that the nanohybrids are more thermally stable than their counterparts. The chlorogenate shows a sustained release, and the release rate of chlorogenate from CZAE and CZAC nanohybrids at pH 7.4 is remarkably lower than that at pH 4.8 due to their different release mechanisms. The release rate of chlorogenate from both nanohybrids can be described as pseudo-second order. The present investigation revealed the potential of the nanohybrids to enhance the in vitro anti-tumour effect of chlorogenic acid in liver and lung cancer cells in vitro. - Highlights: • We intercalated chlorogenic into Zn/Al-layered double hydroxide by ion-exchange and coprecipitation methods. • The two methods gave nanocomposites

  5. Drug delivery system for an anticancer agent, chlorogenate-Zn/Al-layered double hydroxide nanohybrid synthesised using direct co-precipitation and ion exchange methods

    International Nuclear Information System (INIS)

    A nano-structured drug-inorganic clay hybrid involving an active anticancer compound, which is chlorogenic acid (CA) intercalated into Zn/Al-layered double hydroxide, has been assembled via ion-exchange and co-precipitation methods to form a nanohybrid CZAE (a chlorogenic acid-Zn/Al nanohybrid synthesised using an ion-exchange method) and CZAC (a chlorogenic acid-Zn/Al nanohybrid synthesised using a direct method), respectively. The X-ray diffraction (XRD) results confirmed that the CA-LDH had a hybrid structure in which the anionic chlorogenate is arranged between the interlayers as a horizontal monolayer at 90 and 20° angles from the x axis for CZAE and CZAC, respectively. Both nanohybrids have the properties of mesoporous materials. The high loading percentage of chlorogenic acid (approximately 43.2% for CZAE and 45.3% for CZAC) with basal spacings of 11.7 and 12.6 Å for CZAE and CZAC, respectively, corroborates the successful intercalation of chlorogenic acid into the interlayer gallery of layered double hydroxides. Free chlorogenic acid and the synthesised nanocomposites (CZAE, CZAC) were assessed for their cytotoxicity against various cancer cells. The Fourier transform infrared data supported the formation of both nanohybrids, and a thermal analysis showed that the nanohybrids are more thermally stable than their counterparts. The chlorogenate shows a sustained release, and the release rate of chlorogenate from CZAE and CZAC nanohybrids at pH 7.4 is remarkably lower than that at pH 4.8 due to their different release mechanisms. The release rate of chlorogenate from both nanohybrids can be described as pseudo-second order. The present investigation revealed the potential of the nanohybrids to enhance the in vitro anti-tumour effect of chlorogenic acid in liver and lung cancer cells in vitro. - Highlights: • We intercalated chlorogenic into Zn/Al-layered double hydroxide by ion-exchange and coprecipitation methods. • The two methods gave nanocomposites

  6. Improved Total Synthesis and Biological Evaluation of Potent Apratoxin S4 Based Anticancer Agents with Differential Stability and Further Enhanced Activity

    OpenAIRE

    Chen, Qi-Yin; Liu, Yanxia; Cai, Weijing; Luesch, Hendrik

    2014-01-01

    Apratoxins are cytotoxic natural products originally isolated from marine cyanobacteria that act by preventing cotranslational translocation early in the secretory pathway to downregulate receptor levels and inhibit growth factor secretion, leading to potent antiproliferative activity. Through rational design and total synthesis of an apratoxin A/E hybrid, apratoxin S4 (1a), we have previously improved the antitumor activity and tolerability in vivo. Compound 1a and newly designed analogues a...

  7. A Survey of Marine Natural Compounds and Their Derivatives with Anti-Cancer Activity Reported in 2011

    Directory of Open Access Journals (Sweden)

    Marc Diederich

    2013-03-01

    Full Text Available Cancer continues to be a major public health problem despite the efforts that have been made in the search for novel drugs and treatments. The current sources sought for the discovery of new molecules are plants, animals and minerals. During the past decade, the search for anticancer agents of marine origin to fight chemo-resistance has increased greatly. Each year, several novel anticancer molecules are isolated from marine organisms and represent a renewed hope for cancer therapy. The study of structure-function relationships has allowed synthesis of analogues with increased efficacy and less toxicity. In this report, we aim to review 42 compounds of marine origin and their derivatives that were published in 2011 as promising anticancer compounds.

  8. Anti-cancer Effects of Novel Flavonoid Vicenin-2 as a Single Agent and in Synergistic Combination with Docetaxel in Prostate Cancer

    OpenAIRE

    Nagaprashantha, Lokesh Dalasanur; Vatsyayan, Rit; Singhal, Jyotsana; Fast, Spence; Roby, Rhonda; Awasthi, Sanjay; SINGHAL, SHARAD S.

    2011-01-01

    The present study was conducted to determine the efficacy of novel flavonoid vicenin-2 (VCN-2), an active constituent of the medicinal herb Ocimum Sanctum Linn or Tulsi, as a single agent and in combination with docetaxel (DTL) in carcinoma of prostate (CaP). VCN-2 effectively induced anti-proliferative, anti-angiogenic and pro-apoptotic effect in CaP cells (PC-3, DU-145 and LNCaP) irrespective of their androgen responsiveness or p53 status. VCN-2 inhibited EGFR/Akt/mTOR/ p70S6K pathway along...

  9. Anticancer Molecular Mechanisms of Resveratrol

    Science.gov (United States)

    Varoni, Elena M.; Lo Faro, Alfredo Fabrizio; Sharifi-Rad, Javad; Iriti, Marcello

    2016-01-01

    Resveratrol is a pleiotropic phytochemical belonging to the stilbene family. Though it is only significantly present in grape products, a huge amount of preclinical studies investigated its anticancer properties in a plethora of cellular and animal models. Molecular mechanisms of resveratrol involved signaling pathways related to extracellular growth factors and receptor tyrosine kinases; formation of multiprotein complexes and cell metabolism; cell proliferation and genome instability; cytoplasmic tyrosine kinase signaling (cytokine, integrin, and developmental pathways); signal transduction by the transforming growth factor-β super-family; apoptosis and inflammation; and immune surveillance and hormone signaling. Resveratrol also showed a promising role to counteract multidrug resistance: in adjuvant therapy, associated with 5-fluoruracyl and cisplatin, resveratrol had additive and/or synergistic effects increasing the chemosensitization of cancer cells. Resveratrol, by acting on diverse mechanisms simultaneously, has been emphasized as a promising, multi-target, anticancer agent, relevant in both cancer prevention and treatment.

  10. Species clarification of Isaria isolates used as biocontrol agents against Diaphorina citri (Hemiptera: Liviidae) in Mexico.

    Science.gov (United States)

    Gallou, Adrien; Serna-Domínguez, María G; Berlanga-Padilla, Angélica M; Ayala-Zermeño, Miguel A; Mellín-Rosas, Marco A; Montesinos-Matías, Roberto; Arredondo-Bernal, Hugo C

    2016-03-01

    Entomopathogenic fungi belonging to the genus Isaria (Hypocreales: Cordycipitaceae) are promising candidates for microbial control of insect pests. Currently, the Mexican government is developing a biological control program based on extensive application of Isaria isolates against Diaphorina citri (Hemiptera: Liviidae), a vector of citrus huanglongbing disease. Previous research identified three promising Isaria isolates (CHE-CNRCB 303, 305, and 307; tentatively identified as Isaria fumosorosea) from Mexico. The goal of this work was to obtain a complete morphological and molecular characterization of these isolates. Comparative analysis of morphology established that the isolates showed similar characteristics to Isaria javanica. Multi-gene analysis confirmed the morphological identification by including the three isolates within the I. javanica clade. Additionally, this work demonstrated the misidentifications of three other Isaria isolates (CHE-CNRCB 310 and 324: I. javanica, formerly I. fumosorosea; CHE-CNRCB 393: I. fumosorosea, formerly Isaria farinosa), underlying the need for a full and correct characterization of an isolate before developing a biological control program. Finally, the inter-simple sequence repeat (ISSR) genotyping method revealed that the CHE-CNRCB 303, 305, and 307 isolates belong to three different genotypes. This result indicates that ISSR markers could be used as a tool to monitor their presence in field conditions. PMID:26895870

  11. Mycoparasitic and Antagonistic Inhibition on Phytophthora cinnamomi Rands by Microbial Agents Isolated from Manure Composts

    Directory of Open Access Journals (Sweden)

    I. Nyoman Pugeg Aryantha

    2006-01-01

    Full Text Available We isolated bacteria and fungi from composted chicken, sheep, cow and horse manure and screened each isolate for their ability to suppress P. cinnamomi in dual-culture in vitro assays. Of the 180 isolates, including 31 actinomycetes, 64 fungi, 44 fluorescent pseudomonads and 41 endospore-forming bacteria, 45 isolates significantly inhibited the growth of P. cinnamomi on plates. The inhibitory microbes included 24 fungi (including Trichoderma sp., Gliocladium penicillioides and Fusarium sp., 0 actinomycetes (all Streptomyces sp., 7 fluorescent pseudomonads (Pseudomonas sp. and 4 endospore-forming bacteria (Bacillus sp.. The most common mode of action observed was antibiosis, although mycoparasitism, indicated by parallel hyphal growth, hyphal coiling, appressorium formation and direct penetration, was also observed with one isolate of Trichoderma. These results help to explain the role of microbes in the suppression and biological control of P. cinnamomi by composted manures.

  12. Synthesis of α,β-Unsaturated Carbonyl-Based Compounds, Oxime and Oxime Ether Analogs as Potential Anticancer Agents for Overcoming Cancer Multidrug Resistance by Modulation of Efflux Pumps in Tumor Cells.

    Science.gov (United States)

    Qin, Hua-Li; Leng, Jing; Zhang, Cheng-Pan; Jantan, Ibrahim; Amjad, Muhammad Wahab; Sher, Muhammad; Naeem-Ul-Hassan, Muhammad; Hussain, Muhammad Ajaz; Bukhari, Syed Nasir Abbas

    2016-04-14

    Sixty-nine novel α,β-unsaturated carbonyl based compounds, including cyclohexanone, tetralone, oxime, and oxime ether analogs, were synthesized. The antiproliferative activity determined by using seven different human cancer cell lines provided a structure-activity relationship. Compound 8ag exhibited high antiproliferative activity against Panc-1, PaCa-2, A-549, and PC-3 cell lines, with IC50 value of 0.02 μM, comparable to the positive control Erlotinib. The ten most active antiproliferative compounds were assessed for mechanistic effects on BRAF(V600E), EGFR TK kinases, and tubulin polymerization, and were investigated in vitro to reverse efflux-mediated resistance developed by cancer cells. Compound 8af exhibited the most potent BRAF(V600E) inhibitory activity with an IC50 value of 0.9 μM. Oxime analog 7o displayed the most potent EGFR TK inhibitory activity with an IC50 of 0.07 μM, which was analogous to the positive control. Some analogs including 7f, 8af, and 8ag showed a dual role as anticancer and MDR reversal agents. PMID:27010345

  13. In Vitro Activity of Antimicrobial Agents Against Streptococcus Pyogenes Isolates from patients with Acute Tonsillopharyngitis in Dakar, Senegal

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    A. Gueye Ndiaye

    2009-06-01

    Full Text Available Streptococcus pyogenes (S. pyogenes is the most important causative agent of tonsillopharyngitis. Beta-lactam antibiotics, particularly penicillin, are the drug of first choice and macrolides are recommended for patients who are allergic to penicillin. However, other antibiotics are also used for the treatment of streptococcal tonsillopharyngitis. In recent years, the increase in the incidence of respiratory tract pathogens that are resistant to current antibacterial agents highlights the need to monitor the evolution of the resistance of these pathogens to antibiotics. In this study, we assess the susceptibility of 98 isolates of S. pyogenes to 16 antibiotics. The pathogens were recovered from patients with acute tonsillopharyngitis in Dakar, the Senegalese capital city, who were recruited from May 2005 to August 2006. All strains were susceptible to penicillin with low Minimum Inhibitory Concentration (MIC = 0,016 mg/L. Amoxicillin had high activity (100% showing its importance in treatment of streptococcal infections. Cephalosporins had MIC90 values ranging from 0.016 to 0.094 mg/L. Macrolides have shown high activity. All strains were resistant to tetracyclin. Other molecules such as teicoplanin, levofloxacin and chloramphenicol were also active and would represent alternatives to treatment of tonsillopharyngitis due to this pathogen. These results indicate that no significant resistance to antibiotics was found among patients with tonsillopharyngitis studied in Dakar. Limitations of this study were that the number of isolates tested was small and all isolates were collected from one hospital in Dakar. Hence, results may not be representative of the isolates found, in the wider community or other regions of Senegal. Further studies are needed in other parts of Dakar and other geographic regions of Senegal, in order to better clarify the antibiotic susceptibility profile of S. pyogenes isolates recovered from patients with tonsillopharyngitis.

  14. Determination of the new anticancer agent KW 2149, 7-N-[2-[2-(gamma-L-glutamylamino)ethyl)dithio)ethyl]mitomycin C, an analogue of mitomycin C.

    Science.gov (United States)

    Pattyn, G; van Oosterom, A T; de Bruijn, E A; Tjaden, U R

    1991-03-01

    The new mitomycin 7-N-[2-[2-(gamma-L-glutamylamino)ethyl)dithio)ethyl] mitomycin C (KW 2149) (I) proved to be active against a wide variety of experimental tumours. In order to perform pharmacokinetic studies with the new drug in Phase I sessions, a fast and reliable method has been developed based on the data of previous assays for mitomycin C. XAD-2 was preferred for isolation of I from blood plasma. The recovery of I was 50% whereas that of mitomycin C was 85%. Optimal separation was obtained on octadecyl silica columns with methanol-water (45:55, v/v) as mobile phase, while ultraviolet absorbance detection was performed at 375 nm. The assay enabled determination of I in a plasma concentration range of 20-1000 ng/ml using porfiromycin as internal standard. PMID:1860933

  15. Susceptibility of Clinical Candida Species Isolates to Antifungal Agents by E-Test, Southern Iran: A Five Year Study

    Directory of Open Access Journals (Sweden)

    A Alborzi

    2011-12-01

    Full Text Available Background and Objectives: The incidence of fungal infections in immunocompromised patients, especially by Candida species, has increased in recent years. This study was designed to identify Candida species and determine antifungal susceptibility patterns of 595 yeast strains isolated from various clinical specimens.Material and Methods: Identification of the isolates were determined by the API 20 C AUX kit and antifungal susceptibilities of the species to fluconazole, amphotericin B, ketoconazole, itraconazole, voriconazole, and caspofungin were determined by the agar-based E-test method.Results: Candida albicans (48% was the most frequently isolated species, followed by Candida kruzei (16.1%, Candida glabrata (13.5%, Candida kefyr (7.4%, Candida parapsilosis (4.8%, Candida tropicalis (1.7% and other species (8.5%. Resistance varies depending on the species and the respective antifungal agents. Comparing the MIC90 for all the strains, the lower MIC90 was observed for caspofungin (0.5 μg/ml. The MIC90 for all Candida species were 64 μg/ml for fluconazole, 0.75 μg/ml for amphotericin B, 4 μg/ml for ketoconazole, 4 μg/ml for itraconazole, and 2 μg/ml for voriconazole.Conclusions: Species definition and determination of antifungal susceptibility patterns are advised for the proper management and treatment of patients at risk for systemic candidiasis. Resistance to antifungal agents is an alarming sign for the emerging common nosocomial fungal infections.

  16. [Sensitivity surveillance of Streptococcus pneumoniae isolates for several antibacterial agents in Gifu and Aichi prefectures (2011-2012)].

    Science.gov (United States)

    Funatsu, Tori; Mizunaga, Shingo; Fukuda, Yoshiko; Nomura, Nobuhiko; Hashido, Hikonori; Mitsuyama, Junichi; Hatano, Masakazu; Yamaoka, Kazukiyo; Watanabe, Kunitomo; Asano, Yuko; Suematsu, Hiroyuki; Sawamura, Haruki; Matsukawa, Yoko; Ohta, Hirotoshi; Yamagishi, Yuka; Mikamo, Hiroshige; Matsubara, Shigenori; Shibata, Naohiro

    2015-08-01

    We investigated the susceptibility to antibacterial agents, genotype of penicillin-binding protein (PBP) genes and macrolide resistant genes, and the serotypes against 270 strains of Streptococcus pneumoniae isolated from medical facilities in Gifu and Aichi prefectures between October 2011 and April 2012. These results were compared with those against S. pneumoniae isolated in 2008-2009 and 2010-2011. The number of gPSSP with 3 normal PBP genes, gPISP with 1 or 2 normal PBP genes and gPRSP with 3 abnormal genes isolated in 2011-2012 was 15 (5.6%), 162 (60.0%) and 93 (34.4%) strains, respectively. Compared with those isolated in 2008-2009 and 2010-2011, the numbers of gPRSP were decreasing. On the other hand, the isolates with no macrolide-resistant gene, only mefA, only ermB, and both mefA and ermB were 16 (5.9%), 75 (27.8%), 153 (56.7%) and 26 (9.6%). Compared with those isolated in 2008-2009 and 2010-2011, the numbers of isolates with ermB, which was usually associated with high-level resistance, were increasing. The prevalent pneumococcal serotypes in children were type 3 (14.4%), following by type 15 and 19F (9.3%). The coverages of 7-valent pneumococcal conjugate vaccine (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) were calculated as 22.9% and 49.2%, respectively. The coverages of PCV7 and PCV13 in gPRSP isolated from children were 47.7% (21/44 strains) and 72.7% (32/44 strains). The MIC90 of each antibacterial agent was as follows; 0.125pg/mL for imipenem, panipenem and garenoxacin, 0.25 μg/mL for meropenem and doripenem, 0.5 μg/mL for cefditoren, moxifloxacin and tosufloxacin, 1 μg/mL for amoxicillin, clavulanic acid/amoxicillin, cefteram, cefcapene and ceftriaxone, 2 μg/mL for benzylpenicillin, ampicillin, sulbactam/ampicillin, piperacillin, tazobactam/piperacillin and levofloxacin, 4 μg/mL for cefdinir, flomoxef and pazufloxacin, 16 μg/mL for minocycline, > 64 μg/mL for clarithromycin and azithromycin, and these MIC90s were about the

  17. Whole-Genome Sequences of Two Borrelia afzelii and Two Borrelia garinii Lyme Disease Agent Isolates

    Energy Technology Data Exchange (ETDEWEB)

    Casjens, S.R.; Dunn, J.; Mongodin, E. F.; Qiu, W.-G.; Luft, B. J.; Fraser-Liggett, C. M.; Schutzer, S. E.

    2011-12-01

    Human Lyme disease is commonly caused by several species of spirochetes in the Borrelia genus. In Eurasia these species are largely Borrelia afzelii, B. garinii, B. burgdorferi, and B. bavariensis sp. nov. Whole-genome sequencing is an excellent tool for investigating and understanding the influence of bacterial diversity on the pathogenesis and etiology of Lyme disease. We report here the whole-genome sequences of four isolates from two of the Borrelia species that cause human Lyme disease, B. afzelii isolates ACA-1 and PKo and B. garinii isolates PBr and Far04.

  18. THE JOURNAL OF TROPICAL LIFE SCIENCE OPEN ACCESS Freely available online VOL. 5, NO. 2, pp. 88-91, May, 2015 Isolation of an Anti-Cancer Asperuloside from Hedyotis corymbosa L.

    Directory of Open Access Journals (Sweden)

    Nina Artanti

    2015-05-01

    Full Text Available Hedyotis corymbosa L., with local name rumput mutiara, is an anti-inflammatory, anti-cancer and hepatoprotective traditional medicine. The ethanol extract of H. corymbosa L. shows inhibitory activity to humanYMB-1 breast cancer cell line with an IC50 of 6.51 μg/mL. The methylene chloride fraction shows a potential cytotoxic activity with an IC50 of 2.75 μg/mL. To obtain a lead compound, the extract was further purified by column chromatography. A pure compound is obtained which shows inhibitory activities against YMB-1, HL60 and KB human cell lines with IC50 values of 0.7; 11.0 and 104.2 μg/mL, respectively. Based on the 1D and 2D FT-NMR data, the isolated compound is an asperuloside.

  19. 盐霉素——一种新型的抗肿瘤药物%Salinomycin—a potential novel anticancer agent

    Institute of Scientific and Technical Information of China (English)

    王凡; 郭传勇

    2013-01-01

    盐霉素在过去30多年中被广泛应用于防治家禽的球虫病和提高反刍动物的饲料吸收率.2009年,研究者首先发现盐霉素可以选择性的杀伤乳腺癌肿瘤干细胞,且其效率比紫杉醇高出100多倍.此后,越来越多的研究者在体内、体外实验中发现盐霉素可以抑制多种肿瘤干细胞(结直肠癌肿瘤干细胞,肺癌肿瘤干细胞,胰腺癌肿瘤干细胞)的生长,克服肿瘤细胞由P53基因突变,Bcl-2、26S蛋白酶体、p-糖蛋白的过表达引起的凋亡抵抗,增加肿瘤细胞的DNA损伤,激活肿瘤细胞的氧化应激,抑制肿瘤细胞中Wnt信号通路的活性,此外盐霉素还可以增加肿瘤细胞对药物治疗的敏感性.所以盐霉素有希望成为一个新型的化疗药物被用于抗肿瘤的治疗中.%Salinomycin has been used as a veterinary antibiotic to prevent coccidiosis in poultry and to improve nutrient absorption in ruminants for more than 30 years.In 2009 researchers firstly found that salinomycin would selectively kill breast cancer stem cells,further studies revealed that salinomycin inhibited the growth of variety of cancer stem cells including colorectal,lung and pancreatic cancer stem cells.The agent can overcome the resistance of cancer cell apoptosis caused by P53 gene mutation,the over-expression of Bcl-2 protein,26S proteasome and P-glycoprotein; the agent can increase DNA damage,activate oxidative stress,inhibit Wnt signaling pathway and enhance the sensitivity of tumor cells to drug therapy.Salinomycin may be used as a novel chemotherapy drug in the future.

  20. Isolation and identification of actinomycetes from a compost-amended soil with potential as biocontrol agents.

    Science.gov (United States)

    Cuesta, Gonzalo; García-de-la-Fuente, Rosana; Abad, Manuel; Fornes, Fernando

    2012-03-01

    The search for new biocontrol strategies to inhibit the growth of phytopathogenic microorganisms has become widely widespread due to environmental concerns. Among actinomycetes, Streptomyces species have been extensively studied since they have been recognized as important sources of antibiotics. Actinomycete strains were isolated from a calcareous soil, 2 two-phase olive mill waste ('alperujo') composts, and the compost-amended soil by using selective media, and they were then co-cultured with 5 phytopathogenic fungi and 1 bacterium to perform an in vitro antagonism assay. Forty-nine actinomycete strains were isolated, 12 of them showing a great antagonistic activity towards the phytopathogenic microorganisms tested. Isolated strains were identified by 16S rDNA sequence analysis and phenotypic procedures. Eleven isolates concerned the genus Streptomyces and 1 actinomycete with chitinolytic activity belonged to the genus Lechevalieria. PMID:21190787

  1. An Improved High Yield Total Synthesis and Cytotoxicity Study of the Marine Alkaloid Neoamphimedine: An ATP-Competitive Inhibitor of Topoisomerase IIα and Potent Anticancer Agent

    Directory of Open Access Journals (Sweden)

    Linfeng Li

    2014-09-01

    Full Text Available Recently, we characterized neoamphimedine (neo as an ATP-competitive inhibitor of the ATPase domain of human Topoisomerase IIα. Thus far, neo is the only pyridoacridine with this mechanism of action. One limiting factor in the development of neo as a therapeutic agent has been access to sufficient amounts of material for biological testing. Although there are two reported syntheses of neo, both require 12 steps with low overall yields (≤6%. In this article, we report an improved total synthesis of neo achieved in 10 steps with a 25% overall yield. In addition, we report an expanded cytotoxicity study using a panel of human cancer cell lines, including: breast, colorectal, lung, and leukemia. Neo displays potent cytotoxicity (nM IC50 values in all, with significant potency against colorectal cancer (lowest IC50 = 6 nM. We show that neo is cytotoxic not cytostatic, and that neo exerts cytotoxicity by inducing G2-M cell cycle arrest and apoptosis.

  2. Isolation, Characterization, and Identification of Biological Control Agent for Potato Soft Rot in Bangladesh

    OpenAIRE

    Rahman, M.M.; M. E. Ali; Khan, A. A.; Akanda, A. M.; Uddin, Md. Kamal; Hashim, U.; Abd Hamid, S. B.

    2012-01-01

    A total of 91 isolates of probable antagonistic bacteria of potato soft rot bacterium Erwinia carotovora subsp. carotovora (Ecc) were extracted from rhizospheres and endophytes of various crop plants, different soil varieties, and atmospheres in the potato farming areas of Bangladesh. Antibacterial activity of the isolated probable antagonistic bacteria was tested in vitro against the previously identified most common and most virulent soft rot causing bacterial strain Ecc P-138. Only two iso...

  3. Cloning of Toluene 4-Monooxygenase Genes and Application of Two-Phase System to the Production of the Anticancer Agent, Indirubin.

    Science.gov (United States)

    Wongsaroj, Lampet; Sallabhan, Ratiboot; Dubbs, James M; Mongkolsuk, Skorn; Loprasert, Suvit

    2015-08-01

    Indirubin is a strong inhibitor of several eukaryotic cell signaling pathways and shows promise as a treatment for myelocytic leukemia and Alzheimer's disease. The tmoABCDEF operon, encoding the components of a novel toluene 4-monooxygenase from the paint factory soil isolate, Pseudomonas sp. M4, was cloned and expressed in Escherichia coli. E. coli::pKSR12 expressing the tmo genes was used to develop a two-phase [dioctyl phthalate (DOP)/aqueous medium] culture system that was optimized to obtain maximal yields of indirubin from the starting substrate, indole. DOP was used as the organic phase to solubilize and sequester the toxic indole substrate, making possible the use of high indole concentrations that would otherwise interfere with growth in aqueous media. A 50 % (v/v) DOP two-phase system using tryptophan medium containing 3 mM cysteine, 5 mM indole, and 1 mM isatin yielded 102.4 mg/L of indirubin with no conversion of indole to the less valuable alternate product, indigo. PMID:25779640

  4. ANTAGONISTIC EFFECT OF FOUR FUNGAL ISOLATES TO GANODERMA BONINENSE, THE CAUSAL AGENT OF BASAL STEM ROT OF OIL PALM

    Directory of Open Access Journals (Sweden)

    OKKY SETYAWATI DHARMAPUTRA

    1990-01-01

    Full Text Available Four fungal isolates from soils obtained from three sites of the oil palm plantations in North Sumatra were found antagonistic to Ganoderma boninense, the causal agent of basal stem rot of oil palm. Penicillium citrinum inhibited the growth of the pathogen and formed a zone of inhibition on the agar media. Trichoderma harzianum BIO - 1 as well as BIO - 2 and T. viride not only repressed the growth of the pathogen but also caused lysis of the hyphae, and the colony was totally overgrown by the antagonists.

  5. In vitro activities of 18 antimicrobial agents against Staphylococcus aureus isolates from the Institut Pasteur of Madagascar

    Directory of Open Access Journals (Sweden)

    Grosjean Pierre

    2007-05-01

    Full Text Available Abstract Background Staphylococcus aureus, one of the most frequently isolated pathogens in both hospitals and the community, has been particularly efficient at developing resistance to antimicrobial agents. In developed countries, as methicillin-resistant S. aureus (MRSA has prevailed and, furthermore, as S. aureus with reduced susceptibility to vancomycin has emerged, the therapeutic options for the treatment of S. aureus infections have become limited. In developing countries and especially African countries very little is known concerning the resistance of S. aureus to antibiotics. In Madagascar no data exist concerning this resistance. Objective To update the current status of antibiotic resistance of S. aureus in Antananarivo, Madagascar. Methods Clinical S. aureus isolates were collected from patients at the Institut Pasteur of Madagascar from January 2001 to December 2005. Susceptibility tests with 18 antibiotics were performed by the disk diffusion method. Results Among a total of 574 isolates, 506 were from community-acquired infections and 68 from nosocomial infections. There was no significant difference in the methicillin resistance rate between community-acquired strains (33 of 506; 6.5% and nosocomial strains (3 of 68, 4.4%. Many MRSA isolates were resistant to multiple classes of antibiotics. Resistance to tetracyclin, trimethoprim-sulfamethoxazole and erythromycin was more common. Among MRSA isolates resistance rates to rifampicin, fusidic acid, gentamicin and ciprofloxacin were lower than that observed with other drugs easily available in Madagascar. No isolates were resistant to glycopeptides. Conclusion The rate of methicillin-resistant S. aureus is not different between community-acquired and nosocomial infections and is still rather low in Madagascar.

  6. Yeasts isolated from figs (Ficus carica L.) as biocontrol agents of postharvest fruit diseases.

    Science.gov (United States)

    Ruiz-Moyano, S; Martín, A; Villalobos, M C; Calle, A; Serradilla, M J; Córdoba, M G; Hernández, A

    2016-08-01

    Fresh fruit is highly perishable during postharvest life, mainly due to fungal growth. Thus, fungal control is an important goal for the fruit industry. In this work, a selection of antagonistic yeasts isolated from fig and breba crops were screened in vitro. The isolated yeasts were challenged with three moulds isolated from decayed figs and breba crops, identified as Penicillium expansum M639 and Cladosporium cladosporioides M310 and M624, and pathogenic moulds Botrytis cinerea CECT20518 and Monilia laxa CA1 from culture collections. Two yeast isolates, Hanseniaspora opuntiae L479 and Metschnikowia pulcherrima L672, were selected for their ability to inhibit the growth of aforementioned moulds. These yeasts reduced the radial growth of moulds on PDA by between 45.23% and 66.09%. Antagonistic activity was associated with the interaction of live yeast cells with moulds. M. pulcherrima L672 apparently parasitised C. cladosporioides isolates. In addition, challenges were assayed using wounded apples and nectarines, with significant reductions in percent infection and lesion size for all moulds tested. To our knowledge, this is the first report identifying H. opuntiae as an antagonist against different pathogenic moulds. PMID:27052701

  7. Isolation and identification of actinomycetes from a compost-amended soils biocontrol agents

    International Nuclear Information System (INIS)

    Compost capability to suppress soil-borne plant pathogens has become an interesting subject as a strategy for reducing the adverse effects of massive fungicides application in the environmental. In this context, actinomycetes have received considerable attention as biocontrol agents, particularly Streptomyces species. (Author)

  8. Isolation and identification of actinomycetes from a compost-amended soils biocontrol agents

    Energy Technology Data Exchange (ETDEWEB)

    Garcia de la Fuente, R.; Cuesta, G.; Fornes, F.; Abad, M.

    2009-07-01

    Compost capability to suppress soil-borne plant pathogens has become an interesting subject as a strategy for reducing the adverse effects of massive fungicides application in the environmental. In this context, actinomycetes have received considerable attention as biocontrol agents, particularly Streptomyces species. (Author)

  9. Thiosemicarbazone Cu(II) and Zn(II) complexes as potential anticancer agents: syntheses, crystal structure, DNA cleavage, cytotoxicity and apoptosis induction activity.

    Science.gov (United States)

    Shao, Jia; Ma, Zhong-Ying; Li, Ang; Liu, Ya-Hong; Xie, Cheng-Zhi; Qiang, Zhao-Yan; Xu, Jing-Yuan

    2014-07-01

    Four novel thiosemicarbazone metal complexes, [Cu(Am4M)(OAc)]·H2O (1), [Zn(HAm4M)Cl2] (2), [Zn2(Am4M)2Br2] (3) and [Zn2(Am4M)2(OAc)2]·2MeOH (4) [HAm4M=(Z)-2-(amino(pyridin-2-yl)methylene)-N-methylhydrazinecarbothioamide], have been synthesized and characterized by X-ray crystallography, elemental analysis, ESI-MS and IR. X-ray analysis revealed that complexes 1 and 2 are mononuclear, which possess residual coordination sites for Cu(II) ion in 1 and good leaving groups (Cl(-)) for Zn(II) ion in 2. Both 3 and 4 displayed dinuclear units, in which the metal atoms are doubly bridged by S atoms of two Am4M(-) ligands in 3 and by two acetate ions in bi- and mono-dentate forms, respectively, in 4. Their antiproliferative activities on human epithelial cervical cancer cell line (HeLa), human liver hepatocellular carcinoma cell line (HepG-2) and human gastric cancer cell line (SGC-7901) were screened. Inspiringly, IC50 value (11.2±0.9 μM) of complex 1 against HepG-2 cells was nearly 0.5 fold of that against human hepatic cell lines LO2, showing a lower toxicity to human liver cells. Additionally, it displayed a stronger inhibition on the viability of HepG-2 cells than cisplatin (IC50=25±3.1 μM), suggesting complex 1 might be a potential high efficient antitumor agent. Furthermore, fluorescence microscopic observation and flow cytometric analysis revealed that complex 1 could significantly suppress HepG-2 cell viability and induce apoptosis. Several indexes, such as DNA cleavage, reactive oxygen species (ROS) generation, comet assay and cell cycle analysis indicated that the antitumor mechanism of complex 1 on HepG-2 cells might be via ROS-triggered apoptosis pathway. PMID:24690556

  10. Pharmacogenetics of anticancer drugs in non-Hodgkin lymphomas

    OpenAIRE

    Loni, L; Tacca, M Del; Danesi, R

    2001-01-01

    The variability of tumour responses to chemotherapeutic agents is a topic of major interest in current oncology research. Advances in the knowledge of molecular pathology of cancer make available strategies by which tumour cells can be profiled for their genetic background in order to select anticancer agents that might selectively kill cells in a molecular context that matches the mechanism of action of drugs. The next generation of anticancer treatments might thus be tailored on the basis o...

  11. Anticancer activity of Cynodon dactylon and Oxalis corniculata on Hep2 cell line.

    Science.gov (United States)

    Salahuddin, H; Mansoor, Q; Batool, R; Farooqi, A A; Mahmood, T; Ismail, M

    2016-01-01

    Bioactive chemicals isolated from plants have attracted considerable attention over the years and overwhelmingly increasing laboratory findings are emphasizing on tumor suppressing properties of these natural agents in genetically and chemically induced animal carcinogenesis models. We studied in vitro anticancer activity of organic extracts of Cynodon dactylon and Oxalis corniculata on Hep2 cell line and it was compared with normal human corneal epithelial cells (HCEC) by using MTT assay. Real Time PCR was conducted for p53 and PTEN genes in treated cancer cell line. DNA fragmentation assay was also carried out to note DNA damaging effects of the extracts. The minimally effective concentration of ethanolic extract of Cynodon dactylon and methanolic extract of Oxalis corniculata that was nontoxic to HCEC but toxic to Hep2 was recorded (IC50) at a concentration of 0.042mg/ml (49.48 % cell death) and 0.048mg/ml (47.93% cell death) respectively, which was comparable to the positive control. Our results indicated dose dependent increase in cell death. P53 and PTEN did not show significant increase in treated cell line. Moreover, DNA damaging effects were also not detected in treated cancer cell line. Anticancer activity of these plants on the cancer cell line showed the presence of anticancer components which should be characterized to be used as anticancer therapy. PMID:27188871

  12. Isolation and evaluation of bacteria and fungi as biological control agents against Rhizoctonia solani.

    Science.gov (United States)

    Lahlali, R; Bajii, M; Jijakli, M H

    2007-01-01

    Rhizoctonia solani is one of the most important limiting factors for potato production and storage in Belgium and worldwide. Its management is still strongly dependent on chemical treatments. The aim of this work was to evaluate the possibility of exploiting bacteria and fungi in order to control this pathogen. Among a collection of 220 bacterial strains isolated from different organs of healthy potato plants and rhizospheric soils, 25 isolates were selected using screening methods based on in vitro dual culture assays. The mycelial growth inhibition rate of the pathogen was ranged from 59.4 to 95.0%. Also seven fungal strains isolated from the rhizospheric soil and potato roots showed a highly mycelial growth inhibition of R. solani. The mycelial growth inhibition rate obtained with these fungi was included between 60.0 and 99.4%. From this preliminary study, the further investigations will be planned to determine the bacterial isolates systematic, species of fungal strains by using molecular tools and to assess their efficacy against R. solani in greenhouse trials. PMID:18396837

  13. Isolation of 2-deoxyecdysterone, a novel oxytocic agent, from a marine Zoanthus sp.

    Digital Repository Service at National Institute of Oceanography (India)

    Parameswaran, P.S.; Naik, C.G.; Gonsalves, C.; Achuthankutty, C.T.

    The insect-moulting hormone 2-deoxyecdysterone (2-deoxy-20-hydroxyecdysone 1) has been isolated for the first time and in relatively high yield (0.016%) from a marine Zoanthus sp. The compound exhibited promising oxytocic activity in guinea pig...

  14. The Main Anticancer Bullets of the Chinese Medicinal Herb, Thunder God Vine

    Directory of Open Access Journals (Sweden)

    Zi Liu

    2011-06-01

    Full Text Available The thunder god vine or Tripterygium wilfordii Hook. F. is a representative Chinese medicinal herb which has been used widely and successfully for centuries in treating inflammatory diseases. More than 100 components have been isolated from this plant, and most of them have potent therapeutic efficacy for a variety of autoimmune and inflammatory diseases. In the past four decades, the anticancer activities of the extracts from this medicinal herb have attracted intensive attention by researchers worldwide. The diterpenoid epoxide triptolide and the quinone triterpene celastrol are two important bioactive ingredients that show a divergent therapeutic profile and can perturb multiple signal pathways. Both compounds promise to turn traditional medicines into modern drugs. In this review, we will mainly address the anticancer activities and mechanisms of action of these two agents and briefly describe some other antitumor components of the thunder god vine.

  15. Isolation, Identification, and Characterization of Novel Arenaviruses, the Etiological Agents of Boid Inclusion Body Disease

    OpenAIRE

    Hetzel, U; Sironen, T.; Laurinmaki, P.; Liljeroos, L.; Patjas, A.; Henttonen, H.; Vaheri, A; Artelt, A.; Kipar, A.; Butcher, S. J.; Vapalahti, O; Hepojoki, J.

    2013-01-01

    Boid inclusion body disease (BIBD) is a progressive, usually fatal disease of constrictor snakes, characterized by cytoplasmic inclusion bodies (IB) in a wide range of cell types. To identify the causative agent of the disease, we established cell cultures from BIBD-positive and -negative boa constrictors. The IB phenotype was maintained in cultured cells of affected animals, and supernatants from these cultures caused the phenotype in cultures originating from BIBD-negative snakes. Viruses w...

  16. In silico identification of anti-cancer compounds and plants from traditional Chinese medicine database

    OpenAIRE

    Shao-Xing Dai; Wen-Xing Li; Fei-Fei Han; Yi-Cheng Guo; Jun-Juan Zheng; Jia-Qian Liu; Qian Wang; Yue-Dong Gao; Gong-Hua Li; Jing-Fei Huang

    2016-01-01

    There is a constant demand to develop new, effective, and affordable anti-cancer drugs. The traditional Chinese medicine (TCM) is a valuable and alternative resource for identifying novel anti-cancer agents. In this study, we aim to identify the anti-cancer compounds and plants from the TCM database by using cheminformatics. We first predicted 5278 anti-cancer compounds from TCM database. The top 346 compounds were highly potent active in the 60 cell lines test. Similarity analysis revealed t...

  17. The anticancer agent di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) overcomes prosurvival autophagy by two mechanisms: persistent induction of autophagosome synthesis and impairment of lysosomal integrity.

    Science.gov (United States)

    Gutierrez, Elaine; Richardson, Des R; Jansson, Patric J

    2014-11-28

    Autophagy functions as a survival mechanism during cellular stress and contributes to resistance against anticancer agents. The selective antitumor and antimetastatic chelator di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) causes lysosomal membrane permeabilization and cell death. Considering the integral role of lysosomes in autophagy and cell death, it was important to assess the effect of Dp44mT on autophagy to further understand its mechanism of action. Notably, Dp44mT affected autophagy by two mechanisms. First, concurrent with its antiproliferative activity, Dp44mT increased the expression of the classical autophagic marker LC3-II as a result of induced autophagosome synthesis. Second, this effect was supplemented by a reduction in autophagosome degradation as shown by the accumulation of the autophagic substrate and receptor p62. Conversely, the classical iron chelator desferrioxamine induced autophagosome accumulation only by inhibiting autophagosome degradation. The formation of redox-active iron or copper Dp44mT complexes was critical for its dual effect on autophagy. The cytoprotective antioxidant N-acetylcysteine inhibited Dp44mT-induced autophagosome synthesis and p62 accumulation. Importantly, Dp44mT inhibited autophagosome degradation via lysosomal disruption. This effect prevented the fusion of lysosomes with autophagosomes to form autolysosomes, which is crucial for the completion of the autophagic process. The antiproliferative activity of Dp44mT was suppressed by Beclin1 and ATG5 silencing, indicating the role of persistent autophagosome synthesis in Dp44mT-induced cell death. These studies demonstrate that Dp44mT can overcome the prosurvival activity of autophagy in cancer cells by utilizing this process to potentiate cell death. PMID:25301941

  18. Antimicrobial susceptibility pattern of bacterial isolates from wound infection and their sensitivity to antibiotic agents at super specialty hospital, Amravati city, India

    Directory of Open Access Journals (Sweden)

    Hrishikesh Sawdekar

    2015-02-01

    Full Text Available Background: Wound infection is one of the health problems that is caused and aggravated by the invasion of pathogenic organisms. Information on local pathogens and sensitivity to antimicrobial agent is crucial for successful treatment of wounds. So the present study was conducted to determine antimicrobial susceptibility pattern of bacterial isolates from wound infection and their sensitivity to antimicrobial agents. Methods: A retrospective study was conducted among patients with wound infection in Suyash super speciality hospital, from January 2012 to December 2013. Wound swab was collected using sterile cotton swabs and processed for bacterial isolation and susceptibility testing to Systemic antimicrobial agents. Results: In this study 78 bacterial isolates were recovered from 258 specimens showing an isolation rate of 31.2%. The predominant bacteria isolated from wounds were gram positive staphylococci 36 (46.2%, followed by gram negative streptococci 18 (23.1% gram negative pseudomonas 12 (15.4 % and gram negative proteus 8 (10.4%. The gram positive and gram negative bacteria constituted 68 (87.2% and 10 (12.8% of bacterial isolates; respectively. Conclusion: In the present study most of the pathogens isolated from wound isolates showed high rate of resistance to most commonly used newer antibiotics used to treat bacterial infections. Therefore, rational use of antibiotics should be practiced. [Int J Res Med Sci 2015; 3(2.000: 433-439

  19. Propolis as an antibacterial agent against clinical isolates of mdr-acinetobacter baumannii

    International Nuclear Information System (INIS)

    Multidrug resistant (MDR) Acinetobacter baumannii has emerged as an important health care problem. The organism is now identified as an important nosocomial pathogen particularly in the intensive care settings. The therapeutic options to treat this pathogen are limited; thus it needs testing for alternatives, like those of plant origin or natural products. Propolis is one of such products which have been tested against this organism. Methods: A. baumannii (n=32) were collected from Fatima Memorial Hospital, Lahore. The isolates were identified on the basis of their morphology, cultural characteristics and biochemical profile. The susceptibility of the isolates to various antimicrobials was evaluated as per Kirby-Bauer disc diffusion method according to (CLSI 2010). An ethanolic extract of propolis was prepared by the ultrasonic extraction method and its antibacterial activity was evaluated by the agar well diffusion technique. Minimum inhibitory concentration (MIC) was also determined by the agar dilution technique. Results: The isolates were found to be resistant to most of the commonly used anti-acinetobacter antimicrobials; doxycycline however was the exception. Propolis from Sargodha (EPS) and Lahore (EPL) showed zones of inhibition of 21.8 ± .29 mm and 15.66 ± 2.18 mm respectively. MIC ranges of EPS and EPL similarly was from 1.5-2.0 mg/ml and 4.0-4.5 mg/ml respectively. Conclusion: It is clear that EPS has potential edge of activity as compared to EPL. Nevertheless the potential efficacy of propolis must be subjected to pharmaceutical kinetics and dynamics to precisely determine its potential antimicrobial usefulness. (author)

  20. Liposomal Drug Delivery of Anticancer Agents

    DEFF Research Database (Denmark)

    Pedersen, Palle Jacob

    -trans retinoic acid, α-tocopheryl succinate and calcitriol were examined for their ability to be incorporated into the investigated drug delivery system and syntheses of the phospholipid prodrugs are described. The majority of the phospholipid prodrugs were able to form particles with diameters close to 100 nm...

  1. Development of Advanced Macrosphelides: Potent Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Seung-Mann Paek

    2015-03-01

    Full Text Available Synthetic approaches to macrosphelide derivatives, based on medicinal chemistry, are summarized. This review contains conventional medicinal chemistry approaches, combinatorial chemistry, fluorous tagging techniques and affinity chromatography preparation. In addition, advances in their apoptosis-inducing activities are also included.

  2. Development of Advanced Macrosphelides: Potent Anticancer Agents

    OpenAIRE

    Seung-Mann Paek

    2015-01-01

    Synthetic approaches to macrosphelide derivatives, based on medicinal chemistry, are summarized. This review contains conventional medicinal chemistry approaches, combinatorial chemistry, fluorous tagging techniques and affinity chromatography preparation. In addition, advances in their apoptosis-inducing activities are also included.

  3. Development of advanced macrosphelides: potent anticancer agents.

    Science.gov (United States)

    Paek, Seung-Mann

    2015-01-01

    Synthetic approaches to macrosphelide derivatives, based on medicinal chemistry, are summarized. This review contains conventional medicinal chemistry approaches, combinatorial chemistry, fluorous tagging techniques and affinity chromatography preparation. In addition, advances in their apoptosis-inducing activities are also included. PMID:25764486

  4. Selective anticancer agents suppress aging in Drosophila.

    Science.gov (United States)

    Danilov, Anton; Shaposhnikov, Mikhail; Plyusnina, Ekaterina; Kogan, Valeria; Fedichev, Peter; Moskalev, Alexey

    2013-09-01

    Mutations of the PI3K, TOR, iNOS, and NF-κB genes increase lifespan of model organisms and reduce the risk of some aging-associated diseases. We studied the effects of inhibitors of PI3K (wortmannin), TOR (rapamycin), iNOS (1400W), NF-κB (pyrrolidin dithiocarbamate and QNZ), and the combined effects of inhibitors: PI3K (wortmannin) and TOR (rapamycin), NF-κB (pyrrolidin dithiocarbamates) and PI3K (wortmannin), NF-κB (pyrrolidine dithiocarbamates) and TOR (rapamycin) on Drosophila melanogaster lifespan and quality of life (locomotor activity and fertility). Our data demonstrate that pharmacological inhibition of PI3K, TOR, NF-κB, and iNOS increases lifespan of Drosophila without decreasing quality of life. The greatest lifespan expanding effect was achieved by a combination of rapamycin (5 μM) and wortmannin (5 μM) (by 23.4%). The bioinformatic analysis (KEGG, REACTOME.PATH, DOLite, and GO.BP) showed the greatest aging-suppressor activity of rapamycin, consistent with experimental data. PMID:24096697

  5. Mitochondrially targeted anti-cancer agents

    Czech Academy of Sciences Publication Activity Database

    Biasutto, L.; Dong, L.A.; Zoratti, M.; Neužil, Jiří

    2010-01-01

    Roč. 10, č. 6 (2010), s. 670-681. ISSN 1567-7249 Institutional research plan: CEZ:AV0Z50520701 Keywords : Mitochondrial target ing * pro-oxidant effect * reactive oxygen species Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.238, year: 2010

  6. Anti-cancer agents counteracting tumor glycolysis

    OpenAIRE

    Granchi, Carlotta; Minutolo, Filippo

    2012-01-01

    Can we consider cancer as a “metabolic disease”? Tumors are the result of a metabolic selection, forming tissues composed of heterogeneous cells that generally express an overactive metabolism as a common feature. In fact, cancer cells have to deal with increased needs for both energy and biosynthetic intermediates, in order to support their growth and invasiveness. However, their high proliferation rate often generates regions that are not sufficiently oxygenated. Therefore, their carbohydra...

  7. Anticancer potential of animal venoms and toxins.

    Science.gov (United States)

    Gomes, Antony; Bhattacharjee, Pushpak; Mishra, Roshnara; Biswas, Ajoy K; Dasgupta, Subir Chandra; Giri, Biplab

    2010-02-01

    Anticancer drug development from natural resources are ventured throughout the world. Animal venoms and toxins a potential bio resource and a therapeutic tool were known to man for centuries through folk and traditional knowledge. The biodiversity of venoms and toxins made it a unique source of leads and structural templates from which new therapeutic agents may be developed. Venoms of several animal species (snake, scorpion, toad, frog etc) and their active components (protein and non protein toxins, peptides, enzymes, etc) have shown therapeutic potential against cancer. In the present review, the anticancer potential of venoms and toxins from snakes, scorpions, toads and frogs has been discussed. Some of these molecules are in the clinical trials and may find their way towards anticancer drug development in the near future. The implications of combination therapy of natural products in cancer have been discussed. PMID:20455317

  8. CancerHSP: anticancer herbs database of systems pharmacology

    Science.gov (United States)

    Tao, Weiyang; Li, Bohui; Gao, Shuo; Bai, Yaofei; Shar, Piar Ali; Zhang, Wenjuan; Guo, Zihu; Sun, Ke; Fu, Yingxue; Huang, Chao; Zheng, Chunli; Mu, Jiexin; Pei, Tianli; Wang, Yuan; Li, Yan; Wang, Yonghua

    2015-06-01

    The numerous natural products and their bioactivity potentially afford an extraordinary resource for new drug discovery and have been employed in cancer treatment. However, the underlying pharmacological mechanisms of most natural anticancer compounds remain elusive, which has become one of the major obstacles in developing novel effective anticancer agents. Here, to address these unmet needs, we developed an anticancer herbs database of systems pharmacology (CancerHSP), which records anticancer herbs related information through manual curation. Currently, CancerHSP contains 2439 anticancer herbal medicines with 3575 anticancer ingredients. For each ingredient, the molecular structure and nine key ADME parameters are provided. Moreover, we also provide the anticancer activities of these compounds based on 492 different cancer cell lines. Further, the protein targets of the compounds are predicted by state-of-art methods or collected from literatures. CancerHSP will help reveal the molecular mechanisms of natural anticancer products and accelerate anticancer drug development, especially facilitate future investigations on drug repositioning and drug discovery. CancerHSP is freely available on the web at http://lsp.nwsuaf.edu.cn/CancerHSP.php.

  9. Size controlled biogenic silver nanoparticles as antibacterial agent against isolates from HIV infected patients

    Science.gov (United States)

    Suganya, K. S. Uma; Govindaraju, K.; Kumar, V. Ganesh; Dhas, T. Stalin; Karthick, V.; Singaravelu, G.; Elanchezhiyan, M.

    2015-06-01

    Silver nanoparticles (AgNPs) are synthesized using biological sources due to its high specificity in biomedical applications. Herein, we report the size and shape controlled synthesis of AgNPs using the aqueous extract of blue green alga, Spirulina platensis. Size, shape and elemental composition of AgNPs were characterized using UV-vis spectroscopy, Fluorescence spectroscopy, FT-IR (Fourier Transform-Infrared Spectroscopy), FT-RS (Fourier Transform-Raman Spectroscopy), SEM-EDAX (Scanning Electron Microscopy-Energy Dispersive X-ray analysis) and HR-TEM (High Resolution Transmission Electron Microscopy). AgNPs were stable, well defined and monodispersed (spherical) with an average size of 6 nm. The synthesized AgNPs were tested for its antibacterial potency against isolates obtained from HIV patients.

  10. In vivo evaluation on the effects of HemoHIM in promoting anticancer activities and reducing the side-effects of anticancer drugs

    International Nuclear Information System (INIS)

    In this project, we aimed to obtain the preclinical in vivo evaluation data for the development of the herbal composition (HemoHIM) as the auxiliary agent for the anticancer treatment that can reduce the side-effects of anticancer drugs and enhance their anticancer activities. Firstly, in vitro studies showed that HemoHIM did not show any effects on the tumor cell growth inhibition by 2 anticancer drugs (cisplatin, 5-FU), which indicated that at least HemoHIM does not exert any adverse effects on the activities of anticancer drugs. Next, the in vivo studies with mice implanted with tumor cells(B16F0, LLC1) showed that HemoHIM partially enhanced the anticancer activities of drugs (cisplatin, 5-FU), and improved endogenous anticancer immune activities. Furthermore, in the same animal models, HemoHIM effectively reduced the side-effects of anticancer drugs (liver and renal toxicities by cisplatin, immune and hematopoietic disorders by 5-FU). These results collectively showed that HemoHIM can enhance the activities of anticancer drugs and reduce their side-effects in vitro and in vivo and HemoHIM does not exert any adverse effects on the efficacy of anticancer drugs. The results of this project can be utilized as the basic preclinical data for the development and approval of HemoHIM as the auxiliary agent for the anticancer treatment

  11. In vivo evaluation on the effects of HemoHIM in promoting anticancer activities and reducing the side-effects of anticancer drugs

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Sung Kee; Jung, U Hee; Park, Hae Ran; Ju, Eun Jin; Cho, Eun Hee

    2009-07-15

    In this project, we aimed to obtain the preclinical in vivo evaluation data for the development of the herbal composition (HemoHIM) as the auxiliary agent for the anticancer treatment that can reduce the side-effects of anticancer drugs and enhance their anticancer activities. Firstly, in vitro studies showed that HemoHIM did not show any effects on the tumor cell growth inhibition by 2 anticancer drugs (cisplatin, 5-FU), which indicated that at least HemoHIM does not exert any adverse effects on the activities of anticancer drugs. Next, the in vivo studies with mice implanted with tumor cells(B16F0, LLC1) showed that HemoHIM partially enhanced the anticancer activities of drugs (cisplatin, 5-FU), and improved endogenous anticancer immune activities. Furthermore, in the same animal models, HemoHIM effectively reduced the side-effects of anticancer drugs (liver and renal toxicities by cisplatin, immune and hematopoietic disorders by 5-FU). These results collectively showed that HemoHIM can enhance the activities of anticancer drugs and reduce their side-effects in vitro and in vivo and HemoHIM does not exert any adverse effects on the efficacy of anticancer drugs. The results of this project can be utilized as the basic preclinical data for the development and approval of HemoHIM as the auxiliary agent for the anticancer treatment

  12. Reduced Susceptibility to Rifampicin and Resistance to Multiple Antimicrobial Agents among Brucella abortus Isolates from Cattle in Brazil

    Science.gov (United States)

    Barbosa Pauletti, Rebeca; Reinato Stynen, Ana Paula; Pinto da Silva Mol, Juliana; Seles Dorneles, Elaine Maria; Alves, Telma Maria; de Sousa Moura Souto, Monalisa; Minharro, Silvia; Heinemann, Marcos Bryan; Lage, Andrey Pereira

    2015-01-01

    This study aimed to determine the susceptibility profile of Brazilian Brucella abortus isolates from cattle to eight antimicrobial agents that are recommended for the treatment of human brucellosis and to correlate the susceptibility patterns with origin, biotype and MLVA16-genotype of the strains. Screening of 147 B. abortus strains showed 100% sensitivity to doxycycline and ofloxacin, one (0.68%) strain resistant to ciprofloxacin, two strains (1.36%) resistant to streptomycin, two strains (1.36%) resistant to trimethoprim-sulfamethoxazole and five strains (3.40%) resistant to gentamicin. For rifampicin, three strains (2.04%) were resistant and 54 strains (36.73%) showed reduced sensitivity. Two strains were considered multidrug resistant. In conclusion, the majority of B. abortus strains isolated from cattle in Brazil were sensitive to the antimicrobials commonly used for the treatment of human brucellosis; however, a considerable proportion of strains showed reduced susceptibility to rifampicin and two strains were considered multidrug resistant. Moreover, there was no correlation among the drug susceptibility pattern, origin, biotype and MLVA16-genotypes of these strains. PMID:26181775

  13. Use of scintillometric quantitation of unscheduled DNA synthesis in isolated rat hepatocytes for the screening of genotoxic agents

    International Nuclear Information System (INIS)

    The induction of unscheduled DNA synthesis has been considered as a suitable endpoint for the screening of genotoxic agents. Experimentally, unscheduled DNA synthesis is most frequently measured by autoradiography. The purpose of this report was to examine the usefulness of the liquid scintillation counting technique in measuring unscheduled DNA synthesis response in isolated rat hepatocytes. The various liquid scintillation counting-based unscheduled DNA synthesis assay procedures were examined according to the following groupings: (1) procedures based on the acid precipitation of cellular macromolecules, (2) procedures based on isopycnic gradient centrifugation of solubilized cells, (3) procedures based on nuclei isolation in conjunction with other DNA purification methods, and (4) procedures based on the selective retention of hepatocellular DNA. Limited cases in which test chemicals gave positive unscheduled DNA synthesis response in liquid scintillation counting-based assays and negative unscheduled DNA synthesis response in autoradiography-based assays are presented. It is concluded that liquid scintillation counting-based unscheduled DNA synthesis assays represent an appropriate system for inclusion in carcinogenicity and mutagenicity testing programs

  14. In silico identification of anti-cancer compounds and plants from traditional Chinese medicine database

    Science.gov (United States)

    Dai, Shao-Xing; Li, Wen-Xing; Han, Fei-Fei; Guo, Yi-Cheng; Zheng, Jun-Juan; Liu, Jia-Qian; Wang, Qian; Gao, Yue-Dong; Li, Gong-Hua; Huang, Jing-Fei

    2016-05-01

    There is a constant demand to develop new, effective, and affordable anti-cancer drugs. The traditional Chinese medicine (TCM) is a valuable and alternative resource for identifying novel anti-cancer agents. In this study, we aim to identify the anti-cancer compounds and plants from the TCM database by using cheminformatics. We first predicted 5278 anti-cancer compounds from TCM database. The top 346 compounds were highly potent active in the 60 cell lines test. Similarity analysis revealed that 75% of the 5278 compounds are highly similar to the approved anti-cancer drugs. Based on the predicted anti-cancer compounds, we identified 57 anti-cancer plants by activity enrichment. The identified plants are widely distributed in 46 genera and 28 families, which broadens the scope of the anti-cancer drug screening. Finally, we constructed a network of predicted anti-cancer plants and approved drugs based on the above results. The network highlighted the supportive role of the predicted plant in the development of anti-cancer drug and suggested different molecular anti-cancer mechanisms of the plants. Our study suggests that the predicted compounds and plants from TCM database offer an attractive starting point and a broader scope to mine for potential anti-cancer agents.

  15. Killer yeasts as biocontrol agents of spoilage yeasts and bacteria isolated from wine

    Directory of Open Access Journals (Sweden)

    Fernández de Ullivarri Miguel

    2014-01-01

    Full Text Available During the winemaking process Saccharomyces cerevisiae is the main yeast species but other yeasts called non-Saccharomyces as well as different species of lactic acid bacteria (LAB are also present. Then, one strategy to prevent or reduce microbial contamination during the winemaking process is the use of killer yeasts. The aim of this study was to evaluate the killer activity (KA of autochthonous yeasts from Northwest region of Argentine (S. cerevisiae Cf8 and Wickerhamomyces anomalus Cf20 on spoilage yeasts and in LAB of the wine. The KA was evaluated using cell-free supernatants obtained from pure and mixed cultures of strains Cf8-Cf20. S. cerevisiae Cf8 showed a growth reduction between 7 and 48% on D. anomala BDa15, P. membranifaciens BPm481 and Z. bailii Bzb317 while W. anomalus Cf20 exhibited KA of 20, 61, 91 and 92% against B. bruxellensis Ld1, D. anomala BDa15, P. membranifaciens BPm481 and P. guilliermondii Cd6, respectively. Killer mixed supernatants showed growth inhibition similar to strain Cf20. Screening against LAB showed that both killer toxins were able to inhibit the growth of L. hilgardii 5w as well as to reduce a 16–31% histamine production by this LAB strain. These results confirm the potential of autochthonous killer yeasts as biocontrol agents in winemaking process. The mixed culture S. cerevisiae Cf8-W. anomalus Cf20 presented a wide range of KA on spoilage yeasts as well as on L. hilgardii. Therefore, the use of killer yeasts as starter cultures would allow producing wines with controlled quality.

  16. Anti-Cancer Potential of a Novel SERM Ormeloxifene

    Science.gov (United States)

    Gara, Rishi Kumar; Sundram, Vasudha; Chauhan, Subhash C.; Jaggi, Meena

    2014-01-01

    Ormeloxifene is a non-steroidal Selective Estrogen Receptor Modulator (SERM) that is used as an oral contraceptive. Recent studies have shown its potent anti-cancer activities in breast, head and neck, and chronic myeloid leukemia cells. Several in vivo and clinical studies have reported that ormeloxifene possesses an excellent therapeutic index and has been well-tolerated, without any haematological, biochemical or histopathological toxicity, even with chronic administration. A reasonably long period of time and an enormous financial commitment are required to develop a lead compound into a clinically approved anti-cancer drug. For these reasons and to circumvent these obstacles, ormeloxifene is a promising candidate on a fast track for the development or repurposing established drugs as anti-cancer agents for cancer treatment. The current review summarizes recent findings on ormeloxifene as an anti-cancer agent and future prospects of this clinically safe pharmacophore. PMID:23895678

  17. Enediyne anticancer antibiotic lidamycin: chemistry, biology and pharmacology.

    Science.gov (United States)

    Shao, Rong-guang; Zhen, Yong-su

    2008-02-01

    The enediyne antibiotics, the potent anticancer agents that contain diyne-ene functional groups, are appreciated for their novel molecular architecture, their remarkable biological activity and their fascinating mechanism of action. Their anticancer activity is apparently due to their ability to damage DNA through radical-mediated hydrogen abstraction. The enediyne antibiotics show markedly cytotoxicities against cancers in vitro and in vivo. Lidamycin is a member of the enediyne anticancer antibiotic family. This review examines lidamycin with particular emphasis on the discovery, the biological properties and its structure-activity relationships. In addition, the possible mechanisms of action of lidamycin are described. Recent progress, particularly in the areas of biosynthesis, and immunoconjugates are highlighted. Finally, the pharmacological applications of lidamycin in cancer therapy and its potential use as anticancer agents are also discussed. PMID:18288918

  18. 'Smartening' anticancer therapeutic nanosystems using biomolecules.

    Science.gov (United States)

    Núñez-Lozano, Rebeca; Cano, Manuel; Pimentel, Belén; de la Cueva-Méndez, Guillermo

    2015-12-01

    To be effective, anticancer agents must induce cell killing in a selective manner, something that is proving difficult to achieve. Drug delivery systems could help to solve problems associated with the lack of selectivity of classical chemotherapeutic agents. However, to realize this, such systems must overcome multiple physiological barriers. For instance, they must evade surveillance by the immune system, attach selectively to target cells, and gain access to their interior. Furthermore, there they must escape endosomal entrapment, and release their cargoes in a controlled manner, without affecting their functionality. Here we review recent efforts aiming at using biomolecules to confer these abilities to bare nanoparticles, to transform them into smart anticancer therapeutic nanosystems. PMID:26277646

  19. Are isothiocyanates potential anti-cancer drugs?

    Institute of Scientific and Technical Information of China (English)

    Xiang WU; Qing-hua ZHOU; Ke XU

    2009-01-01

    Isothiocyanates are naturally occurring small molecules that are formed from glucosinolate precursors of cruciferous vegetables. Many isothiocyanates, both natural and synthetic, display anticarcinogenic activity because they reduce activation of carcinogens and increase their detoxification. Recent studies show that they exhibit anti-tumor activity by affecting multiple pathways including apoptosis, MAPK signaling, oxidative stress, and cell cycle progression. This review summarizes the current knowledge on isothiocyanates and focuses on their role as potential anti-cancer agents.

  20. Polymer anticancer drugs with peptide targeting

    Czech Academy of Sciences Publication Activity Database

    Studenovský, Martin; Pola, Robert; Pechar, Michal; Ulbrich, Karel; Hovorka, Ondřej

    Long Beach : Controlled Release Society, 2007, 771/1-771/2. [Annual Meeting and Exposition of the Controlled Release Society /34./. Long Beach (US), 07.07.2007-11.07.2007] R&D Projects: GA ČR GA204/05/2255 Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z50200510 Keywords : angiogenesis * anticancer agents * conjugates * HPMA copolymers Subject RIV: CE - Biochemistry http://www.controlledreleasesociety.org/meeting/program/pdfs/ProgramBook.pdf

  1. Isolation of cDNAs encoding a human protein that binds selectively to DNA modified by the anticancer drug cis-diammine-dichloroplatinum(II)

    International Nuclear Information System (INIS)

    DNA modified by the antitumor drug cis-diamminedichloroplatinum(II) (cis-DDP or cisplatin) was used to identify a factor in mammalian cells that binds to cis-DDP-damaged DNA and hence may play a role in repair. This factor selectivity recognizes double-stranded DNA fragments modified by cis-DDP or [Pt(en)Cl2] (en, ethylenediamine). Little or no binding occurs to unmodified double-stranded DNA or to DNA modified with the clinically ineffective compounds trans-DDP and [Pt(dien)Cl]Cl (dien, diethylenetriamine). Low levels of binding to single-stranded DNA modified by cis-DDP are observed. The apparent molecular mass of the factor in a variety of mammalian cells is ∼ 100 kDa, as determined by modified Western blotting. Two recombinant phage have been isolated from a human B-cell λgt11 library by using a cis-DDP-modified DNA restriction fragments as a probe. The two clones have insert sizes of 1.88 and 1.44 kilobases and are aligned at their 5' ends. The polypeptides encoded by the recombinant phage exhibit DNA binding properties similar to those of the cellular factor identified in crude extracts prepared from mammalian cells. Northern analysis with one of the clones revealed an mRNA of 2.8 kilobases that is conserved in humans and rodents. The methods used here should be applicable in studies of other damage-specific DNA binding proteins

  2. Anticancer Activity Evaluation of Kuanoniamines A and C Isolated from the Marine Sponge Oceanapia sagittaria, Collected from the Gulf of Thailand

    Directory of Open Access Journals (Sweden)

    Madalena Pinto

    2007-04-01

    Full Text Available The pyridoacridine alkaloids kuanoniamines A and C were isolated together with 24α-methylcholestanol, p-hydroxybenzaldehyde, p-hydroxybenzoic acid, phenylacetic acid and 3-formylindole from the ethyl acetate extract of the marine sponge Oceanapia sagittaria (Sollas, collected from the Gulf of Thailand. Kuanoniamines A and C were evaluated for their effect on the growth of five human tumour and a non-tumour cell lines, as well as on the proliferation of human lymphocytes. Kuanoniamine A was found to be a potent growth inhibitor of all the tumour and a non-tumour cell lines while kuanoniamine C was less potent but showed high selectivity toward the estrogen dependent (ER+ breast cancer cell line. Kuanoniamine A has shown to be a more potent inhibitor of DNA synthesis than kuanoniamine C. Kuanoniamine A was also found to cause an extensive reduction of the MCF-7 cells in G2/M phase as well as an increase in the apoptotic cells.

  3. Tetracycline-resistance encoding plasmids from Paenibacillus larvae, the causal agent of American foulbrood disease, isolated from commercial honeys.

    Science.gov (United States)

    Alippi, Adriana M; León, Ignacio E; López, Ana C

    2014-03-01

    Paenibacillus larvae, the causal agent of American foulbrood disease in honeybees, acquires tetracycline-resistance via native plasmids carrying known tetracycline-resistance determinants. From three P. larvae tetracycline-resistant strains isolated from honeys, 5-kb-circular plasmids with almost identical sequences, designated pPL373 in strain PL373, pPL374 in strain PL374, and pPL395 in strain PL395, were isolated. These plasmids were highly similar (99%) to small tetracycline-encoding plasmids (pMA67, pBHS24, pBSDMV46A, pDMV2, pSU1, pAST4, and pLS55) that replicate by the rolling circle mechanism. Nucleotide sequences comparisons showed that pPL373, pPL374, and pPL395 mainly differed from the previously reported P. larvae plasmid pMA67 in the oriT region and mob genes. These differences suggest alternative mobilization and/or conjugation capacities. Plasmids pPL373, pPL374, and pPL395 were individually transferred by electroporation and stably maintained in tetracycline-susceptible P. larvae NRRL B-14154, in which they autonomously replicated. The presence of nearly identical plasmids in five different genera of gram-positive bacteria, i.e., Bhargavaea, Bacillus, Lactobacillus, Paenibacillus, and Sporosarcina, inhabiting diverse ecological niches provides further evidence of the genetic transfer of tetracycline resistance among environmental bacteria from soils, food, and marine habitats and from pathogenic bacteria such as P. larvae. PMID:25296446

  4. The anticancer potential of steroidal saponin, dioscin, isolated from wild yam (Dioscorea villosa) root extract in invasive human breast cancer cell line MDA-MB-231 in vitro.

    Science.gov (United States)

    Aumsuwan, Pranapda; Khan, Shabana I; Khan, Ikhlas A; Ali, Zulfiqar; Avula, Bharathi; Walker, Larry A; Shariat-Madar, Zia; Helferich, William G; Katzenellenbogen, Benita S; Dasmahapatra, Asok K

    2016-02-01

    Previously, we observed that wild yam (Dioscorea villosa) root extract (WYRE) was able to activate GATA3 in human breast cancer cells targeting epigenome. This study aimed to find out if dioscin (DS), a bioactive compound of WYRE, can modulate GATA3 functions and cellular invasion in human breast cancer cells. MCF-7 and MDA-MB-231 cells were treated in the absence/presence of various concentrations of DS and subjected to gene analysis by RT-qPCR, immunoblotting, and immunocytochemistry. We determined the ability of MDA-MB-231 cells to migrate into wound area and examined the effects of DS on cellular invasion using invasion assay. DS reduced cell viability of both cell lines in a concentration and time-dependent manner. GATA3 expression was enhanced by DS (5.76 μM) in MDA-MB-231 cells. DS (5.76 μM)-treated MDA-MB-231 cells exhibited the morphological characteristic of epithelial-like cells; mRNA expression of DNMT3A, TET2, TET3, ZFPM2 and E-cad were increased while TET1, VIM and MMP9 were decreased. Cellular invasion of MDA-MB-231 was reduced by 65 ± 5% in the presence of 5.76 μM DS. Our data suggested that DS-mediated pathway could promote GATA3 expression at transcription and translation levels. We propose that DS has potential to be used as an anti-invasive agent in breast cancer. PMID:26682631

  5. NMR investigation of the binding of the anticancer drug actinomycin D to oligodeoxyribonucleotides with isolated 5'd(GC)3' binding sites

    International Nuclear Information System (INIS)

    Imino proton and 31P NMR studies were conducted on the binding of actinomycin D (ActD) to self-complementary oligodeoxyribonucleotides with one GC binding site [d(ATATGCATAT) (1), d(ATACGCGTAT) (2), and d(ATATACGCGTATAT) (3)] and with two GC sites [d(ATGCATGCAT) (4)]. At R = 1 (molar ratio of ActD to oligomer duplex) ActD caused a doubling of the number of imino proton signals at, and adjacent to, the GC binding site of 1. One of the G-C base pair signals shifted upfield while the other shifted downfield. Both of the signals for the A-T base pairs adjacent to the binding site shifted downfield. All imino proton signals of 2 and the longer sequence, 3 shifted upfield on binding of ActD to the GC site, indicating a sequence-dependent change in base stacking on complex formation. For both 1 and 2 addition of ActD resulted in a similar pattern of three downfield 31P NMR signals. The two most downfield signals have chemical shift and temperature dependence which are characteristic of phosphate groups at isolated intercalation sites. At R = 1 the ActD complex with 4 has very complex spectra with both upfield and downfield A-T and G-C imino signals. All these data were consistent with two 1:1 complexes with the unsymmetrical phenoxazone ring adopting both of the two possible orientations. The variety of ActD adducts observed for these relatively simple sequences indicates that ActD binding to natural DNA must be much more complex than previously anticipated

  6. Characterization of a Newly Isolated Marine Fungus Aspergillus dimorphicus for Optimized Production of the Anti-Tumor Agent Wentilactones

    Directory of Open Access Journals (Sweden)

    Rui Xu

    2015-11-01

    Full Text Available The potential anti-tumor agent wentilactones were produced by a newly isolated marine fungus Aspergillus dimorphicus. This fungus was derived from deep-sea sediment and identified by polyphasic approach, combining phenotypic, molecular, and extrolite profiles. However, wentilactone production was detected only under static cultures with very low yields. In order to improve wentilactone production, culture conditions were optimized using the response surface methodology. Under the optimal static fermentation conditions, the experimental values were closely consistent with the prediction model. The yields of wentilactone A and B were increased about 11-fold to 13.4 and 6.5 mg/L, respectively. The result was further verified by fermentation scale-up for wentilactone production. Moreover, some small-molecule elicitors were found to have capacity of stimulating wentilactone production. To our knowledge, this is first report of optimized production of tetranorlabdane diterpenoids by a deep-sea derived marine fungus. The present study might be valuable for efficient production of wentilactones and fundamental investigation of the anti-tumor mechanism of norditerpenoids.

  7. Chemical and preclinical studies on Hedyotis diffusa with anticancer potential.

    Science.gov (United States)

    Niu, Yu; Meng, Qiu-Xia

    2013-01-01

    This paper presents the chemical and preclinical anticancer research on Hedyotis diffusa Willd. in detail, one of the most renowned herbs often prescribed in the polyherbal formulas for cancer treatment in traditional Chinese medicine. Anthraquinones, flavonoids, and terpenoids constitute the majority of the 69 compounds that have been isolated and identified from H. diffusa. The anticancer effects of the methanolic, ethanolic, and aqueous extracts in various preclinical cancer models have been described. This review also summarized the anticancer activity of constituents of the herb and the mechanisms of action. All the studies suggest that H. diffusa has enormous potential in the therapy of cancer and warrants further chemical and pharmacological investigation. PMID:23600735

  8. Potential Anti-cancer Activity of Furanodiene

    Institute of Scientific and Technical Information of China (English)

    Zhen-zhen Ba; Yan-ping Zheng; Hui Zhang; Xiu-yan Sun; Dong-hai Lin

    2009-01-01

    Objective: To study the anti-tumor activities of furanodiene (C15H20O), a primary sesquiterpene compound isolated from the essential oil of the rhizome of Curcuma wenyujin YH Chen et C. Ling(Wen Ezhu), in vitro and in vivo.Methods: In vitro MTT assay was used to further study the effects of time and dosage on anti-proliferation of furanodiene against the sensitive Hela, Hep-2,HL-60, U251 cells, based on the cytotoxic effects of furanodiene on 12 human malignant tumor cell lines with the essential oil of Wen Ezhu as control., and the half-inhibitory concentration (IC50) was observed. In vivo uterine cervix (U14) tumor cell was selected and the conventional assay method of anti-tumor activity was employed. Furanodiene liposome was administered intraperitoneally, and tumor-inhibitory rate, thymus and spleen indexes were observed.Results: The inhibitive effects on cell proliferation were shown in all of the twelve cell lines and the cytotoxic effects of furanodiene against Hela, Hep-2, HL-60, U251 cells were observed after 12 h of administration, the effect could last for at least 48 h in a dose dependent manner, and the IC50 values were 0.6, 1.7, 1.8, 7.0 μg/ml, respectively. Furanodiene was also found to show inhibitive effects on the proliferation of uterine cervix (U14) tumor induced in mice. The tumor inhibition rates were 36.09% (40 mg/kg), 41.55% (60 mg/kg), 58.29% (80 mg/kg), respectively.Conclusion: Furanodiene is one of primary anti-cancer active components in the essential oil of Wen Ezhu, and also a very effective agent against uterine cervix cancer, and has protection effect on the immune function.

  9. Anticancer property of sediment actinomycetes against MCF-7 and MDA-MB-231 cell lines

    Institute of Scientific and Technical Information of China (English)

    Ravikumar S; Fredimoses M; Gnanadesigan M

    2012-01-01

    Objective: To investigate the anticancer property of marine sediment actinomycetes against two different breast cancer cell lines. Methods:In vitro anticancer activity was carried out against breast (MCF-7 and MDA-MB-231) cancer cell lines. Partial sequences of the 16s rRNA gene, phylogenetic tree construction, multiple sequence analysis and secondary structure analysis were also carried out with the actinomycetes isolates. Results: Of the selected five actinomycete isolates, ACT01 and ACT02 showed the IC50 value with (10.13±0.92) and (22.34±5.82)μg/mL concentrations, respectively for MCF-7 cell line at 48 h, but ACT01 showed the minimum (18.54±2.49 μg/mL) level of IC50 value with MDA-MB-231 cell line. Further, the 16s rRNA partial sequences of ACT01, ACT02, ACT03, ACT04 and ACT05 isolates were also deposited in NCBI data bank with the accession numbers of GQ478246, GQ478247, GQ478248, GQ478249 and GQ478250, respectively. The phylogenetic tree analysis showed that, the isolates of ACT02 and ACT03 were represented in group I and III, respectively, but ACT01 and ACT02 were represented in group II. The multiple sequence alignment of the actinomycete isolates showed that, the maximum identical conserved regions were identified with the nucleotide regions of 125 to 221st base pairs, 65 to 119th base pairs and 55, 48 and 31st base pairs. Secondary structure prediction of the 16s rRNA showed that, the maximum free energy was consumed with ACT03 isolate (-45.4 kkal/mol) and the minimum free energy was consumed with ACT04 isolate (-57.6 kkal/mol). Conclusions:The actinomycete isolates of ACT01 and ACT02 (GQ478246 and GQ478247) which are isolated from sediment sample can be further used as anticancer agents against breast cancer cell lines.

  10. Phytochemistry and Anticancer Potential of Notoginseng.

    Science.gov (United States)

    Wang, Chong-Zhi; Anderson, Samantha; Yuan, Chun-Su

    2016-01-01

    Asian ginseng, American ginseng, and notoginseng are three major species in the ginseng family. Notoginseng is a Chinese herbal medicine with a long history of use in many Oriental countries. This botanical has a distinct ginsenoside profile compared to other ginseng herbs. As a saponin-rich plant, notoginseng could be a good candidate for cancer chemoprevention. However, to date, only relatively limited anticancer studies have been conducted on notoginseng. In this paper, after reviewing its anticancer data, phytochemical isolation and analysis of notoginseng is presented in comparison with Asian ginseng and American ginseng. Over 80 dammarane saponins have been isolated and elucidated from different plant parts of notoginseng, most of them belonging to protopanaxadiol or protopanaxatriol groups. The role of the enteric microbiome in mediating notoginseng metabolism, bioavailability, and pharmacological actions are discussed. Emphasis has been placed on the identification and isolation of enteric microbiome-generated notoginseng metabolites. Future investigations should provide key insights into notoginseng's bioactive metabolites as clinically valuable anticancer compounds. PMID:26916912

  11. Synthesis and characterization of Cu(II)-based anticancer chemotherapeutic agent targeting topoisomerase Iα: in vitro DNA binding, pBR322 cleavage, molecular docking studies and cytotoxicity against human cancer cell lines.

    Science.gov (United States)

    Tabassum, Sartaj; Zaki, Mehvash; Afzal, Mohd; Arjmand, Farukh

    2014-03-01

    New metal-based anticancer chemotherapeutic drug candidates [Cu(phen)L](NO₃)₂ (1) and [Zn(phen)L](NO₃)₂ (2) were synthesized from ligand L (derived from pharmacophore scaffold barbituric acid and pyrazole). In vitro DNA binding studies of the L, 1 and 2 were carried out by various biophysical techniques revealing electrostatic mode. Complex 1 cleaves pBR322 DNA via oxidative pathway and recognizes major groove of DNA double helix. The molecular docking study was carried out to ascertain the mode of action towards the molecular target DNA and enzymes. The complex 1 exhibited remarkably good anticancer activity on a panel of human cancer cell lines (GI₅₀ values < 10 μg/ml), and to elucidate the mechanism of cancer inhibition, Topo-I enzymatic activity was carried out. PMID:24508781

  12. Anticancer Activities of Brassinosteroids

    Czech Academy of Sciences Publication Activity Database

    Hoffmannová, Lucie; Oklešťková, Jana; Steigerová, J.; Kohout, Ladislav; Kolář, Z.; Strnad, Miroslav

    AG Bussum : Bentham Science, 2012 - (Pereira-Netto, A.), s. 84-93 ISBN 978-1-60805-298-1 Grant ostatní: GA AV ČR(CZ) IAA400550801 Institutional research plan: CEZ:AV0Z50380511 Keywords : antiangiogenic activity * anticancer drugs * apoptosis Subject RIV: CC - Organic Chemistry http://home.ueb.cas.cz/publikace/2012_Strnad_chapter.pdf

  13. Synthesis and structure-activity relationship of N-(2-arylethyl) isoquinoline derivatives as anti-cancer agents%N-芳乙基异喹啉衍生物的合成及其抗肿瘤活性研究

    Institute of Scientific and Technical Information of China (English)

    汪燕翔; 赵午莉; 毕重文; 李阳彪; 邵荣光; 宋丹青

    2012-01-01

    A series of novel N-(2-arylethyl) isoquinoline derivatives were designed, synthesized and evaluated for their anti-cancer activities. Among these analogs, compound 9a exhibited the potential anti-cancer activities on HepG2 and HCT116 cells with IC50 values of 2.52 and 1.99 μg·mL-1, respectively. Cell cycle was blocked at S phase of HepG2 cells treated with 9a by flow cytometry detection. Our results provided a basis for the development of a new series of anti-cancer candidates.%本研究采用一种简便的新方法设计合成了一系列全新结构的N-芳乙基异喹啉衍生物,并对其体外抗肿瘤活性进行了评价.其中化合物9a表现出较强的抗肿瘤活性,对人肝癌HepG2和大肠癌HCT116细胞的IC50值分别为2.52和1.99 μg·mL-1.初步作用机制显示,9a可以将HepG2细胞周期阻滞于S期,使细胞增殖受阻,达到抗肿瘤效果.

  14. [Susceptibility of clinically-isolated bacteria strains to respiratory quinolones and evaluation of antimicrobial agent efficacy by Monte Carlo simulation].

    Science.gov (United States)

    Kosaka, Tadashi; Yamada, Yukiji; Kimura, Takeshi; Kodama, Mai; Fujitomo, Yumiko; Masaki, Nakanishi; Toshiaki, Komori; Keisuke, Shikata; Fujita, Naohisa

    2016-02-01

    Respiratory quinolones (RQs) are broad-spectrum antimicrobial agents used for the treatment of a wide variety of community-acquired and nosocomial infections. However, bacterial resistance to quinolones has been on the increase. In this study, we investigated the predicted efficacy of RQs for various strains of 9 bacterial species clinically isolated at our university hospital using the Monte Carlo simulation (MCS) method based on pharmacokinetics/pharmacodynamics modeling. In addition, the influence of the patients' renal function on the efficacy of RQs was evaluated. We surveyed antimicrobial susceptibility testing of 9 bacterial species (n = number of strains) [Streptococcus pneumoniae (n = 15), Streptococcus pyogenes (n = 14), Streptococcus agalactiae (n = 19), methicillin-susceptible Staphylococcus aureus (MSSA) (n = 24), Escherichia coli (n = 35), Haemophilus influenzae (n = 17), Klebsiella pneumoniae (n = 14), Pseudomonas aeruginosa (n = 31), and Moraxella catarrhalis (n = 11)] to 4 RQs [garenoxacin (GRNX), levofloxacin (LVFX), sitafloxacin (STFX), and moxifloxacin (MFLX)]. We found that compared with the other RQs, Gram-positive cocci was most resistant to LVFX, and that the minimum inhibitory concentration (MIC₉₀) values for S. pneumoniae, S. pyogenes, S. agalactiae, and MSSA were high (2, 16, > 16, and 8 µg/mL, respectively). In regard to Gram-negative rods, the susceptibility of E. coli to RQs was found to be decreased, with the MIC₉₀ values of GRNX, LVFX, STFX, and MFLX being > 16, 16, 1, and 16 µg/mL, respectively. MCS revealed that the target attainment rate of the area under the unbound concentration-time curve divided by the MIC₉₀ (ƒ · AUC/MIC ratio), against S. pneumoniae was 86.9-100%, but against E. coli was low (52.1-66.2%). The ƒ · AUC/MIC target attainment rate of LVFX against S. pneumoniae, S. pyogenes, and S. agalactiae tended to decrease due to increased creatinine clearance, and that of LVFX and STFX against MSSA also

  15. [Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1996), III. Secular changes in susceptibility].

    Science.gov (United States)

    Kumamoto, Y; Tsukamoto, T; Hirose, T; Yokoo, A; Shigeta, S; Takahashi, T; Shiraiwa, Y; Ogiwara, M; Yoshida, H; Imafuku, Y; Murai, M; Watanabe, K; Uchida, H; Kobayashi, Y; Matsuda, S; Fujime, M; Fujita, K; Igari, J; Oguri, T; Yamaguchi, K; Matsumoto, T; Kashitani, F; Kaku, M; Ooe, H; Mochida, C

    1998-03-01

    Susceptibilities to various antimicrobial agents were examined for Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella spp., and Pseudomonas aeruginosa that were isolated from patients with urinary tract infections (UTIs) in 10 hospitals during June 1996 to May 1997, and the results were compared with those obtained during the same period in earlier years. 1. E. faecalis Among E. faecalis strains, those with high susceptibilities to ampicillin and minocycline appeared to have decreased in the latest study period. 2. S. aureus To almost antimicrobial agents, S. aureus isolated from uncomplicated UTIs showed low susceptibilities. But the MIC50s of those agents for S. aureus from complicated UTIs have changed better state. Particularly, the MIC50s of imipenem and clindamycin were 0.125 microgram/ml or below in the latest period for the first time in our history. 3. E. coli The susceptibilities to piperacillin and quinolones of E. coli isolated from uncomplicated UTIs were better than those isolated from complicated UTIs. 4. Klebsiella spp. The susceptibilities to almost antimicrobial agents of Klebsiella spp. have been better during the latest period, compared to those during period of 1995-1996, but to ofloxacin and ciprofloxacin have appeared to have been lower. 5. P. aeruginosa The susceptibilities to quinolones of P. aeruginosa have been better during the latest period compared those during periods of 1995-1996. But, the susceptibilities to cefozopran, carbapenems and monobactams of P. aeruginosa isolated from complicated UTIs appeared to have been lower. These susceptibility changes should be utilized in determining clinical treatments. PMID:9597551

  16. In vitro and in vivo Methods for Anticancer Activity Evaluation and Some Indian Medicinal Plants Possessing Anticancer Properties: An Overview

    OpenAIRE

    Sumitra Chanda; Krunal Nagani

    2013-01-01

    Cancer is a major public health burden in both developed and developing countries. Anticancer activity is the effect of natural and synthetic or biological and chemical agents to reverse, suppress or prevent carcinogenic progression. Several synthetic agents are used to cure the disease but they have their toxicity and hence the research is going on to investigate the plant derived chemotherapeutic agents. Therefore an attempt has been made to review different in vitro and in vivo methods for...

  17. Anticancer activity of botanical alkyl hydroquinones attributed to topoisomerase II poisoning

    International Nuclear Information System (INIS)

    Cytotoxic alkyl hydroquinone compounds have been isolated from many plants. We previously isolated 3 structurally similar cytotoxic alkyl hydroquinone compounds from the sap of the lacquer tree Rhus succedanea L. belonging to the sumac family, which have a long history of medicinal use in Asia. Each has an unsaturated alkyl chain attached to the 2-position of a hydroquinone ring. One of these isolates, 10'(Z),13'(E),15'(E)-heptadecatrienylhydroquinone [HQ17(3)], being the most cytotoxic, was chosen for studying the anticancer mechanism of these compounds. We found that HQ17(3) was a topoisomerase (Topo) II poison. It irreversibly inhibited Topo IIα activity through the accumulation of Topo II-DNA cleavable complexes. A cell-based assay showed that HQ17(3) inhibited the growth of leukemia HL-60 cells with an EC50 of 0.9 μM, inhibited the topoisomerase-II-deficient cells HL-60/MX2 with an EC50 of 9.6 μM, and exerted no effect on peripheral blood mononuclear cells at concentrations up to 50 μM. These results suggest that Topo II is the cellular drug target. In HL-60 cells, HQ17(3) promptly inhibited DNA synthesis, induced chromosomal breakage, and led to cell death with an EC50 about one-tenth that of hydroquinone. Pretreatment of the cells with N-acetylcysteine could not attenuate the cytotoxicity and DNA damage induced by HQ17(3). However, N-acetylcysteine did significantly reduce the cytotoxicity of hydroquinone. In F344 rats, intraperitoneal injection of HQ17(3) for 28 days induced no clinical signs of toxicity. These results indicated that HQ17(3) is a potential anticancer agent, and its structural features could be a model for anticancer drug design

  18. Anti-inflammatory and anti-cancer activity of mulberry (Morus alba L.) root bark

    OpenAIRE

    Eo, Hyun Ji; Park, Jae Ho; Park, Gwang Hun; Lee, Man Hyo; Lee, Jeong Rak; Koo, Jin Suk; Jeong, Jin Boo

    2014-01-01

    Background Root bark of mulberry (Morus alba L.) has been used in herbal medicine as anti-phlogistic, liver protective, kidney protective, hypotensive, diuretic, anti-cough and analgesic agent. However, the anti-cancer activity and the potential anti-cancer mechanisms of mulberry root bark have not been elucidated. We performed in vitro study to investigate whether mulberry root bark extract (MRBE) shows anti-inflammatory and anti-cancer activity. Methods In anti-inflammatory activity, NO was...

  19. [Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1995). III. Differences in susceptibilities from previous years].

    Science.gov (United States)

    Kumamoto, Y; Tsukamoto, T; Hirose, T; Yokoo, A; Hikichi, Y; Shigeta, S; Takahashi, T; Shiraiwa, Y; Ogiwara, M; Yoshida, H; Imafuku, Y; Murai, M; Watanabe, K; Uchida, H; Kobayashi, Y; Matsuda, S; Fujime, M; Fujita, K; Igari, J; Oguri, T; Kosakai, N; Yamaguchi, K; Matsumoto, T; Kashitani, F; Mochida, C

    1997-04-01

    Susceptibilities to various antimicrobial agents were examined for Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa that were isolated from patients with urinary tract infections (UTIs) in 11 hospitals during June, 1995 through May, 1996, and the results were compared with those obtained during the same period in earlier years. 1. Macrolide resistant E. faecalis isolated from uncomplicated UTIs during the latest study period appeared to have increased compared to those in previous study periods. More than 50% of the isolated E. faecalis during the latest study period were resistant to macrolide antibiotics, for the first time in our history. 2. No obvious changes were observed through the years for susceptibilities of S. aureus to various antimicrobial agents. Vancomycin (VCM) showed the highest activity against S. aureus, with MICs below 2 micrograms/ml or below. 3. Among E. coli strains, those with low susceptibilities to quinolones appeared to have increased over the years with MIC90 changed from between 0.125 microgram/ml or below and 0.5 microgram/ml in the 1989-1990 period to between 8 micrograms/ml and 128 micrograms/ml in the latest study period. 4. Klebsiella spp. showed higher resistance to most antimicrobial agents during periods of 1993-1994 and 1994-1995, but somewhat lower resistance during period of 1995-1996. No resistant Klebsiella spp. were detected from uncomplicated UTIs during the latest study period. 5. Among P. aeruginosa isolates from complicated UTIs, resistance isolates to gentamicin appeared to be increasing over the years. Resistant strains to quinolones were isolated at lower frequencies during periods of 1991-1994, but higher frequency was observed in the latest period, and MIC50s were between 0.5 and 4 micrograms/ml during 1991-1994, but were 16-32 micrograms/ml during 1995-1996. These susceptibility changes should be utilized in determining clinical treatments. PMID:9192248

  20. Oncolytic viruses as anticancer vaccines

    Directory of Open Access Journals (Sweden)

    Norman eWoller

    2014-07-01

    Full Text Available Oncolytic virotherapy has shown impressive results in preclinical studies and first promising therapeutic outcomes in clinical trials as well. Since viruses are known for a long time as excellent vaccination agents, oncolytic viruses are now designed as novel anticancer agents combining the aspect of lysis-dependent cytoreductive activity with concomitant induction of antitumoral immune responses. Antitumoral immune activation by oncolytic virus infection of tumor tissue comprises both, immediate effects of innate immunity and also adaptive responses for long lasting antitumoral activity which is regarded as the most prominent challenge in clinical oncology. To date, the complex effects of a viral tumor infection on the tumor microenvironment and the consequences for the tumor-infiltrating immune cell compartment are poorly understood. However, there is more and more evidence that a tumor infection by an oncolytic virus opens up a number of options for further immunomodulating interventions such as systemic chemotherapy, generic immunostimulating strategies, dendritic cell-based vaccines, and antigenic libraries to further support clinical efficacy of oncolytic virotherapy.

  1. Initial identification and sensitivity to antimicrobial agents of Salmonella sp.isolated from poultry products in the state of Ceara, Brazil

    Directory of Open Access Journals (Sweden)

    WF Oliveira

    2006-09-01

    Full Text Available The objective of this research was to isolate and to verify the sensitivity to antimicrobial agents of strains of Salmonella sp. isolated from poultry products in the state of Ceara, Brazil. A total number of 114 samples was collected from 63 broiler carcasses derived from two processing plants and two supermarkets, and 51 excreta samples were collected in broiler farms located in the state of Ceara, which used three live production stages. Each excreta sample consisted of a fresh excreta pool from 100 birds. Samples were submitted to microbiological analyses, and the isolated Salmonella strains were tested for antimicrobial sensitivity. No Salmonella was isolated from excreta samples, while broiler carcass samples showed a high contamination rate of11.8%. Three serotypes were identified: Salmonella enterica serovar Enteritidis, 50%; Salmonella enterica serovar Panama 33%, and Salmonella enterica serovar Newport, 17%. As to the susceptibility tests to antimicrobial agents, 100% of the isolated Salmonella strains showed resistance to Ampicillin and Tetracycline, and sensitivity to Gentamycin, Netilmycin, Carbenicillin, Chloramphenicol.

  2. Isolation of Stem rot Disease Causing Organism of Brinjal and their in-vitro Inhibition with Fungicides and Bio-control Agents

    Directory of Open Access Journals (Sweden)

    Shaily Javeria

    2014-09-01

    Full Text Available Different strains of Sclerotinia sclerotiorum were isolated from the diseased samples collected from different hosts and locations. Among the 14 isolates, 12 isolates colonies covered the entire Petri plates within 96 hours but, two isolates from fababean and yellow mustard showed slow colony growth within 96 hours. All isolates produced sclerotia which were varied in number, but the fenugreek isolate produced maximum (43 number of sclerotia and lambs quarter isolate produced minimum number of sclerotia (12 on PDA medium. To examine inhibitory effect of fungicide on the mycelial growth of the pathogen, 9 fungicides were tested in vitro against Sclerotinia sclerotiorum, of those carbendazim, carboxin, topsin-M and carbendazim+ mancozeb (SAAF were found most effective and inhibited the mycelial growth of pathogen up to 100 per cent at 0.05%, 0.1%, and 0.2% concentration. The effect of different bioagents viz., Trichoderma harzianum, T. viride, T. koningii, T. atroviride, T. longibraciatum, Aspergillus niger, Chaetomium globosome and Penicillium notatum in inhibiting the growth of Sclerotinia sclerotiorum was studied through “Dual Culture Technique”. The data showed that among the eight biocontrol agent six were fond effective. The maximum inhibition was found by T. harzianum causing 70.82% inhibition of mycelial growth of the pathogen S. sclerotiorum.

  3. Biocontrol of Botrytis allii Munn the Causal Agent of Neck Rot, the Post Harvest Disease in Onion, by use of a New Iranian Isolate of Streptomyces

    Directory of Open Access Journals (Sweden)

    M. Jorjandi

    2009-01-01

    Full Text Available Problem statement: Soil actinomycetes particularly Streptomyces spp. showed antagonistic activity against wide range of plant pathogens. In the recent decades they have attracted high interests as biocontrol agents. Onion neck rot or gray mold caused by Botrytis allii have imposed economic post harvest damages to onion bulbs and decreased its storage durability and market value. Approach: To investigate for biocontrol means against the pathogen, antagonistic activity of 50 isolates of soil Actinomycetes were assayed through agar disk method and dual culture bioassays. Active isolates were exposed to chloroform for detection of antibiotic. Minimum Inhibitory Concentration (MIC value and solubility of active crude extract in organic solvents were determined for Streptomyces isolate No. 347 which showed a unique and stable property of inhibiting Botrytis allii. To investigate the antagonistic effect of Streptomyces isolate No. 347 on control of onion gray mold, 4 different treatments were tested by means of Tukey HSD test. Results: From the tested isolates, 13 showed anti gray mold activities. Exposure of active isolates to chloroform revealed that Streptomyces isolates No. 347, 263 and 350 retained their antifungal activities. The active metabolite(s of Streptomyces isolate No. 347 was polar, soluble in H2O but insoluble in chloroform and methanol. MIC of the crude was determined as 0.05 mg mL-1 against B. allii. Stability of the active crude in distilled water at room temperature (12-30°C was about 6 months. Statistical studies indicated that Streptomyces isolates No. 347 can decrease losses of neck rot with significant level (pConclusion: The future goals include investigation of the antifungal genes in active isolates as candidates for genetic engineering of onion for increased tolerance against B. allii.

  4. Toxicities of anticancer drugs and its management

    Directory of Open Access Journals (Sweden)

    Ambili Remesh

    2012-02-01

    Full Text Available One of the characteristics that distinguish anticancer agents from other drugs is the frequency and severity of side effects at therapeutic doses. Most cytotoxic drugs target rapidly multiplying cells and the putative targets are the nucleic acids and their precursors, which are rapidly synthesised during cell division. Many solid tumours have a lower growth fraction than the normal bone marrow, gastro intestinal lining, reticuloendothelial system and gonads. Drugs affect these tissues in a dose dependant manner and there is individual susceptibility also. So toxicities are more frequently associated with these tissues. The side effects may be acute or chronic, self-limited, permanent, mild or potentially life threatening. Management of these side effects is of utmost importance because they affect the treatment, tolerability and overall quality of life. This paper gives an overview of different toxicities of anticancer drugs and its management. [Int J Basic Clin Pharmacol 2012; 1(1.000: 2-12

  5. Isocorydine Derivatives and Their Anticancer Activities

    Directory of Open Access Journals (Sweden)

    Mei Zhong

    2014-08-01

    Full Text Available In order to improve the anticancer activity of isocorydine (ICD, ten isocorydine derivatives were prepared through chemical structure modifications, and their in vitro and in vivo activities were experimentally investigated. 8-Amino-isocorydine (8 and 6a,7-dihydrogen-isocorydione (10 could inhibit the growth of human lung (A549, gastric (SGC7901 and liver (HepG2 cancer cell lines in vitro. Isocorydione (2 could inhibit the tumor growth of murine sarcoma S180-bearing mice, and 8-acetamino-isocorydine (11, a pro-drug of 8-amino-isocorydine (8, which is instable in water solution at room temperature, had a good inhibitory effect on murine hepatoma H22-induced tumors. The results suggested that the isocorydine structural modifications at C-8 could significantly improve the biological activity of this alkaloid, indicating its suitability as a lead compound in the development of an effective anticancer agent.

  6. Investigation of risk factors of bovine mastitis in Ethiopia; Isolation of mastitis causing agents and determination of the content of somatic cells in milk

    OpenAIRE

    Frese, Mathias Lutz

    2010-01-01

    In this thesis, the risk factors of bovine mastitis in different milk production systems in Ethiopia were investigated. Furthermore, mastitis causing agents were isolated after California Mastitis Test (CMT) was used as the field test. Somatic cells were counted and compared with the CMT. Low milk production and low quality of milk are apparently related to a lack of proper hygienic measures throughout the farm clusters.

  7. Biological Control of Sclerotinia sclerotiorum, Causal Agent of Sunflower Head and Stem Rot Disease, by Use of Soil borne Actinomycetes Isolates

    Directory of Open Access Journals (Sweden)

    F. Baniasadi

    2009-01-01

    Full Text Available Problem statement: High level of biosafety and non adverse effects on the environment of biocontrol strategies of pest management, are priorities of tomorrow's world agriculture. Actinomycetes are active biocontrol agents due to their antagonistic properties against wide range of plant pathogens particularly fungi. Fungal pathogens are liable for a big part of damages in agriculture economy. Approach: In the present research antifungal bioactivity of 50 isolates of Actinomycetes collected from soils of Kerman province of Iran was investigated against Sclerotinia sclerotiorum (Lib., the causal agent of stem rot in sunflower, through agar disc method and dual culture bioassays. The Streptomyces isolate No. 363 was propagated in submerged cultures and active crude was prepared upon which several biological characterizations performed. Greenhouse studies were achieved to confirm laboratory results. Results: Among the tested Streptomyces isolates, 10 isolates revealed antagonistic properties in dual culture procedure from which isolate No. 363 showed highest bioactivity. The active metabolite of Streptomyces isolate No. 363 was polar and well soluble in H2O. Using agar-disc method, progressive growth of the pathogen was highly reduced by the antagonist through exhibiting ability to constitute fungus-free zones of inhibitions. The results indicated that isolate No. 363 was a proper candidate for field biocontrol studies. Conclusion: Results may open a horizon for production of resistant transgenic plants having antifungal properties originated from biologically active Streptomyces spp. recognition and production of effective metabolite(s of Streptomyces spp. which was responsible for antifungal activities will be our commercial goal due to rich reserves of soil borne Actinomycetes in Iran.

  8. Isolating the roles of different forcing agents in global stratospheric temperature changes using model integrations with incrementally added single forcings

    Science.gov (United States)

    Aquila, V.; Swartz, W. H.; Waugh, D. W.; Colarco, P. R.; Pawson, S.; Polvani, L. M.; Stolarski, R. S.

    2016-07-01

    Satellite instruments show a cooling of global stratospheric temperatures over the whole data record (1979-2014). This cooling is not linear and includes two descending steps in the early 1980s and mid-1990s. The 1979-1995 period is characterized by increasing concentrations of ozone-depleting substances (ODSs) and by the two major volcanic eruptions of El Chichón (1982) and Mount Pinatubo (1991). The 1995-present period is characterized by decreasing ODS concentrations and by the absence of major volcanic eruptions. Greenhouse gas (GHG) concentrations increase over the whole time period. In order to isolate the roles of different forcing agents in the global stratospheric temperature changes, we performed a set of simulations using the NASA Goddard Earth Observing System Chemistry-Climate Model with prescribed sea surface temperatures. We find that in our model simulations the cooling of the stratosphere from 1979 to present is mostly driven by changes in GHG concentrations in the middle and upper stratosphere and by GHG and ODS changes in the lower stratosphere. While the cooling trend caused by increasing GHGs is roughly constant over the satellite era, changing ODS concentrations cause a significant stratospheric cooling only up to the mid-1990s, when they start to decrease because of the implementation of the Montreal Protocol. Sporadic volcanic events and the solar cycle have a distinct signature in the time series of stratospheric temperature anomalies but do not play a statistically significant role in the long-term trends from 1979 to 2014. Several factors combine to produce the step-like behavior in the stratospheric temperatures: in the lower stratosphere, the flattening starting in the mid-1990s is due to the decrease in ozone-depleting substances; Mount Pinatubo and the solar cycle cause the abrupt steps through the aerosol-associated warming and the volcanically induced ozone depletion. In the middle and upper stratosphere, changes in solar

  9. Effects of Slime Produced by Clinical Isolates of Coagulase-Negative Staphylococci on Activities of Various Antimicrobial Agents

    OpenAIRE

    Souli, Maria; Giamarellou, Helen

    1998-01-01

    A novel in vitro semiquantitative method was developed to investigate the influence of staphylococcal slime on the activities of 22 antimicrobial agents. Pefloxacin, teicoplanin, and vancomycin demonstrated remarkable decreases in efficacy: 30, 52, and 63%, respectively. The activity of rifampin was not significantly reduced (0.99%), whereas all other agents tested were modestly affected (

  10. The preventive effect of granisetron on digestive tract symptoms induced by arterial infusion of anticancer and hypertensive agents in combination with radiotherapy. A study of forty patients with bladder cancer

    International Nuclear Information System (INIS)

    Forty patients with bladder cancer who underwent radiotherapy with angiotensin II, a hypertensor, and two cycles of arterial infusion of anticancer chemotherapies, including cisplatin 100 mg/body, were randomly assigned to a granisetron group and a non-granisetron group for comparative study of its prophylactic effect on nausea, vomiting and anorexia. Granisetron proved significantly effective in preventing nausea, as 75% of granisetron-administered patients experienced either only slight nausea or none at all, against only 22.5% in the non-granisetron group. The number of vomiting episodes was zero during the three-day observation period in 28 out of 40 (70%) granisetron-administered patients compared with 6 patients (15%) in the non-granisetron group. A significant difference in prophylactic effect on anorexia was demonstrated between the granisetron and non-granisetron group, indicating that control of alimentary symptoms such as nausea and vomiting influences the severity of anorexia. As to the safety, nausea was lengthened and deteriorated in one patient. Though the physician in charge judged it to be an adverse event too minor to question the safety of granisetron. Thus, granisetron proved to be highly effective and safe in preventing nausea, vomiting and anorexia in patients under concomitant administration of radiotherapy with hypertensor and arterial infusion of anticancer chemotherapies. (author)

  11. Intraperitoneal inoculation of Haemophilus influenzae local isolates in BALB/c mice model in the presence and absence of virulence enhancement agents

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    N Mojgani

    2013-01-01

    Full Text Available Purpose:Haemophilus influenzae (Hi, predominantly type b accounts for approximately 4% of cases of community-acquired and nosocomial meningitis, in adults. The objective of this study was to evaluate the pathogenicity of local Hi isolates (type b, f and non-typable in BALB/c mice in the presence of virulence enhancement agents. Materials and Methods: Three different concentrations of the Hi isolates were inoculated intraperitoneally in BALB/c mice in the presence of 2% hemoglobin and 4% mucin as virulence enhancing agents (VEA. The ability of the isolates to produce bacteremia, the percent survival and lethal dose (LD 50 were recorded in different challenge groups. Results: The 3 Haemophilus influenzae type b (Hib isolates used in study were able to show virulence in BALB/c mice model only in the presence of VEA and their LD 50 decreased significantly when 2% hemoglobin and 4% mucin were used. All survived animals showed bacteremia within 4 h of inoculation which was cleared within 18 h. Significant differences ( P < 0.01 in the virulence and survival percentage of Hib challenge groups were observed based on their dose of inoculation and VEA. None of the isolates were able to induce infection in the absence of VEA. Non-type b isolates failed to produce disease in the mice models even at the highest inoculated dose (10 8 cfu and in the presence of VEA. Conclusions: BALB/c mice appeared suitable for evaluating the virulence of Hib strains, and 2% hemoglobin with 4% mucin an appropriate concentration for inducing infection in this animal model.

  12. NBM-HD-1: A Novel Histone Deacetylase Inhibitor with Anticancer Activity

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    Wei-Jan Huang

    2012-01-01

    Full Text Available HDAC inhibitors (HDACis have been developed as promising anticancer agents in recent years. In this study, we synthesized and characterized a novel HDACi, termed NBM-HD-1. This agent was derived from the semisynthesis of propolin G, isolated from Taiwanese green propolis (TGP, and was shown to be a potent suppressor of tumor cell growth in human breast cancer cells (MCF-7 and MDA-MB-231 and rat glioma cells (C6, with an IC50 ranging from 8.5 to 10.3 μM. Western blot demonstrated that levels of p21(Waf1/Cip1, gelsolin, Ac-histone 4, and Ac-tubulin markedly increased after treatment of cancer cells with NBM-HD-1. After NBM-HD-1 treatment for 1–4 h, p-PTEN and p-AKT levels were markedly decreased. Furthermore, we also found the anticancer activities of NBM-HD-1 in regulating cell cycle regulators. Treatment with NBM-HD-1, p21(Waf1/Cip1 gene expression had markedly increased while cyclin B1 and D1 gene expressions had markedly decreased. On the other hand, we found that NBM-HD-1 increased the expressions of tumor-suppressor gene p53 in a dose-dependent manner. Finally, we showed that NBM-HD-1 exhibited potent antitumor activity in a xenograft model. In conclusion, this study demonstrated that this compound, NBM-HD-1, is a novel and potent HDACi with anticancer activity in vitro and in vivo.

  13. In vitro evaluation of verapamil and other modulating agents in Brazilian chloroquine-resistant Plasmodium falciparum isolates Avaliação in vitro do verapamil e de outros agentes moduladores em isolados de Plasmodium falciparum resistentes à cloroquina

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    Carla M.S. Menezes

    2003-01-01

    Full Text Available Verapamil, was assayed to record its modulating effect upon Brazilian Plasmodium falciparum isolates resistant to chloroquine. Other cardiovascular drugs known to be modulating agents in resistant malaria and/or multidrug-resistant neoplasias, including nifedipine, nitrendipine, diltiazem and propranolol, were also evaluated. Concentrations similar to those for cardiovascular therapy were used in the in vitro microtechnique for antimalarial drug susceptibility. Intrinsic antiplasmodial activity was observed from the lowest concentrations without a significant modulating action. Other reported modulating agents, such as the antipsychotic drug trifluoperazine and the antidepressants desipramine and imipramine, demonstrated similar responses under the same experimental conditions. Results suggest a much higher susceptibility of Brazilian strains, as well as an indifferent behaviour in relation to modulating agents.Verapamil foi ensaiado quanto ao efeito modulador em isolados brasileiros de Plasmodium falciparum resistentes à cloroquina. Outros agentes cardiovasculares, considerados como moduladores da resistência em malária e/ou em neoplasias multiresistentes a fármacos, como nifedipino, nitrendipino, diltiazem e propranolol foram ensaiados quanto ao mesmo efeito. Concentrações semelhantes às da terapia cardiovascular foram empregadas no ensaio de microtécnica de sensibilidade para fármacos antimaláricos. Atividade antiplasmódica intrínsica foi observada desde as menores concentrações, sem, entretanto, ocorrência de modulação significativa da resistência. Sob as mesmas condições experimentais, respostas semelhantes foram observadas para outros agentes moduladores conhecidos como o antipsicótico trifluoperazina e os antidepressivos desipramina e imipramina. Em conjunto, estes resultados sugerem alta sensibilidade e comportamento indiferente de cepas brasileiras ao efeito de agentes moduladores da resistência.

  14. Frequency of resistance to methicillin and other antimicrobial agents among Staphylococcus aureus strains isolated from pigs and their human handlers in Trinidad

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    Annika Gordon

    2014-04-01

    Full Text Available Background: Methicillin-resistant Staphylococcus aureus (MRSA has emerged recently worldwide in production animals, particularly pigs and veal calves, which act as reservoirs for MRSA strains for human infection. The study determined the prevalence of MRSA and other resistant strains of S. aureus isolated from the anterior nares of pigs and human handlers on pig farms in Trinidad. Methods: Isolation of S. aureus was done by concurrently inoculating Baird-Parker agar (BPA and Chromagar MRSA (CHROM with swab samples and isolates were identified using standard methods. Suspect MRSA isolates from Chromagar and BPA were subjected to confirmatory test using Oxoid PBP2 latex agglutination test. The disc diffusion method was used to determine resistance to antimicrobial agents. Results: The frequency of isolation of MRSA was 2.1% (15 of 723 for pigs but 0.0% (0 of 72 for humans. Generally, for isolates of S. aureus from humans there was a high frequency of resistance compared with those from pigs, which had moderate resistance to the following antimicrobials: penicillin G (54.5%, 51.5%, ampicillin (59.1%, 49.5%, and streptomycin (59.1%, 37.1%, respectively. There was moderate resistance to tetracycline (36.4%, 41.2% and gentamycin (27.2%, 23.7% for human and pig S. aureus isolates, respectively, and low resistance to sulfamethoxazole-trimethoprim (4.5%, 6.2% and norfloxacin (9.1%, 12.4%, respectively. The frequency of resistance to oxacillin by the disc method was 36.4 and 34.0% from S. aureus isolates from humans and pigs, respectively. Out of a total of 78 isolates of S. aureus from both human and pig sources that were resistant to oxacillin by the disc diffusion method, only 15 (19.2% were confirmed as MRSA by the PBP'2 latex test kit. Conclusions: The detection of MRSA strains in pigs, albeit at a low frequency, coupled with a high frequency of resistance to commonly used antimicrobial agents in pig and humans could have zoonotic and therapeutic

  15. Sphingolipid metabolism enzymes as targets for anticancer therapy

    NARCIS (Netherlands)

    Kok, JW; Sietsma, H

    2004-01-01

    Treatment with anti-cancer agents in most cases ultimately results in apoptotic cell death of the target tumour cells. Unfortunately, tumour cells can develop multidrug resistance, e.g., by a reduced propensity to engage in apoptosis by which they become insensitive to multiple chemotherapeutics. Ce

  16. Curcumin and its promise as an anticancer drug: An analysis of its anticancer and antifungal effects in cancer and associated complications from invasive fungal infections.

    Science.gov (United States)

    Chen, Jin; He, Zheng-Min; Wang, Feng-Ling; Zhang, Zheng-Sheng; Liu, Xiu-zhen; Zhai, Dan-Dan; Chen, Wei-Dong

    2016-02-01

    Invasive fungal infections (IFI) are important complications of cancer, and they have become a major cause of morbidity and mortality in cancer patients. Effective anti-infection therapy is necessary to inhibit significant deterioration from these infections. However, they are difficult to treat, and increasing antifungal drug resistance often leads to a relapse. Curcumin, a natural component that is isolated from the rhizome of Curcuma longa plants, has attracted great interest among many scientists studying solid cancers over the last half century. Interestingly, curcumin provides an ideal alternative to current therapies because of its relatively safe profile, even at high doses. To date, curcumin's potent antifungal activity against different strains of Candida, Cryptococcus, Aspergillus, Trichosporon and Paracoccidioides have been reported, indicating that curcumin anticancer drugs may also possess an antifungal role, helping cancer patients to resist IFI complications. The aim of this review is to discuss curcumin's dual pharmacological activities regarding its applications as a natural anticancer and antifungal agent. These dual pharmacological activities are expected to lead to clinical trials and to improve infection survival among cancer patients. PMID:26723514

  17. In vitro activity of antimicrobial agents against streptococcus pyogenes isolated from different regions of Khyber Pakhtun Khwa Pakistan.

    Science.gov (United States)

    Rizwan, Muhammad; Bakht, Jehan; Bacha, Nafees; Ahmad, Bashir

    2016-01-01

    The present study investigates the antibiotic resistance of S. pyogenes of 600 isolates collected from different body parts including throat and sputum were analyzed for their antimicrobial susceptibility to 5 antibiotics using the Kirby Bauer disc diffusion method. Based on different identification tests including, gram staining, beta hemolysis, catalase test and bacitracin sensitivity test, a total of 138 isolates were confirmed as S. pyogenes. The prevalence of S. pyogenes was 80% in sore throat and 29% in sputum samples. These isolates were further tested for antibiotics resistance using disk diffusion method. Out of 138 isolates, 49.27% isolates showed resistance towards cefixime, 28.98% towards cefotaxime and 17.39% towards ciprofloxacin, 17.39% towards ampicillin, 17.39% towards erythromycin, 15.94% towards streptomycin, 0.724% isolates towards chloromphenicol and 0% towards penicillin. Among the resistant isolates of S. pyogenes, 60.71% showed resistance towards cefixime, 57.14% towards ciprofloxacin, 57.14% towards streptomycin, 50% towards erythromycin and 25% towards cefotaxime. PMID:26826819

  18. Melatonin Anticancer Effects: Review

    Directory of Open Access Journals (Sweden)

    Luigi Di Bella

    2013-01-01

    Full Text Available Melatonin (N-acetyl-5-methoxytryptamine, MLT, the main hormone produced by the pineal gland, not only regulates circadian rhythm, but also has antioxidant, anti-ageing and immunomodulatory properties. MLT plays an important role in blood composition, medullary dynamics, platelet genesis, vessel endothelia, and in platelet aggregation, leukocyte formula regulation and hemoglobin synthesis. Its significant atoxic, apoptotic, oncostatic, angiogenetic, differentiating and antiproliferative properties against all solid and liquid tumors have also been documented. Thanks, in fact, to its considerable functional versatility, MLT can exert both direct and indirect anticancer effects in factorial synergy with other differentiating, antiproliferative, immunomodulating and trophic molecules that form part of the anticancer treatment formulated by Luigi Di Bella (Di Bella Method, DBM: somatostatin, retinoids, ascorbic acid, vitamin D3, prolactin inhibitors, chondroitin-sulfate. The interaction between MLT and the DBM molecules counters the multiple processes that characterize the neoplastic phenotype (induction, promotion, progression and/or dissemination, tumoral mutation. All these particular characteristics suggest the use of MLT in oncological diseases.

  19. Genetic Variation among Isolates of Sarcocystis neurona, the Agent of Protozoal Myeloencephalitis, as Revealed by Amplified Fragment Length Polymorphism Markers

    OpenAIRE

    Elsheikha, H.M.; Schott, H. C.; Mansfield, L. S.

    2006-01-01

    Sarcocystis neurona causes serious neurological disease in horses and other vertebrates in the Americas. Based on epidemiological data, this parasite has recently emerged. Here, the genetic diversity of Sarcocystis neurona was evaluated using the amplified fragment length polymorphism (AFLP) method. Fifteen S. neurona taxa from different regions collected over the last 10 years were used; six isolates were from clinically diseased horses, eight isolates were from wild-caught opossums (Didelph...

  20. Pathogenicity of local isolate virus BHV-1 as the aetiological agent of Infectious Bovine Rhinotracheitis in Bali Cattle

    Directory of Open Access Journals (Sweden)

    Rini I Damayanti

    2005-10-01

    Full Text Available Infectious Bovine Rhinotracheitis is a disease of cattle characterised by clinical signs of the upper respiratory tract, reproductive tract and nervous system. A study to define the pathogenicity of four BHV-1 local isolates has been conducted. Fourteen Bali cattle that were free of BHV-1 has been selected and divided into four treatment groups. Each group of three was infected with virus isolate I, II, III and IV respectively with approximately a dose of 108TCID50 /10 ml and two cattle were used as control animals. Isolate I and III were originated from semen from IBR positive bulls number G 867 and G 148 respectively whereas isolate II was collected from vaginal mucosa and isolate IV was from nasal mucosa of IBR positive cattle treated with dexamethasone. Clinical response, gross-pathological and histopathological changes were observed. Immunohistochemical staining was applied to detect the antigen in tissue section. The results show that the BHV-1 local isolates could produce IBR syndrome namely fever and changes in the respiratory and reproductive tracts even though the clinical responses seemed to be disappeared by 21 days PI. Grossly there were hyperaemic nasal and vaginal mucosa and pneumonia whereas histologically there were non suppurative rhinitis, tracheitis, pneumonia and vulvovaginitis. Immunohistochemically the antigen was detected in the nasal concha and trachea. Dexamethasone treatment at 60-64 days PI could produce less severe clinical features and the second necroppsy at 69 days PI also results in less severe pathological responses. The findings also suggest that the pathogenicity of BHV-1 local isolates were as follows: isolates I, II, IV and III.

  1. Activity of telavancin and comparator antimicrobial agents tested against Staphylococcus spp. isolated from hospitalised patients in Europe (2007-2008).

    Science.gov (United States)

    Mendes, Rodrigo E; Sader, Helio S; Jones, Ronald N

    2010-10-01

    The activity of telavancin was evaluated against Staphylococcus spp. collected from European hospitals as part of an international surveillance study (2007-2008). A total of 7534 staphylococcal clinical isolates [5726 Staphylococcus aureus and 1808 coagulase-negative staphylococci (CoNS)] were included. Isolates were tested for susceptibility according to reference methods and minimum inhibitory concentration (MIC) values were interpreted based on Clinical and Laboratory Standards Institute (CLSI) 2010 and European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2009 criteria. Telavancin breakpoints approved by the US Food and Drug Administration (FDA) were applied. Telavancin activity was evaluated against meticillin-resistant S. aureus (MRSA) displaying several antibiogram resistance patterns, including multidrug-resistant isolates. Telavancin was active against S. aureus [MIC(50/90) values (MICs for 50% and 90% of the isolates, respectively)=0.12/0.25mg/L; 100.0% susceptible] and CoNS (MIC(50/90)=0.12/0.25mg/L), inhibiting all isolates at quinupristin/dalfopristin, vancomycin and linezolid). Based upon MIC(90) values, telavancin demonstrated potent in vitro activity against a contemporary (2007-2008) collection of Staphylococcus spp. recovered from nearly 30 European medical centres. PMID:20598860

  2. In vitro activity of dalbavancin and five comparator agents against common and uncommon Gram-positive organisms isolated from cancer patients.

    Science.gov (United States)

    Rolston, Kenneth V I; Wang, Weiqun; Nesher, Lior; Shelburne, Samuel A; Prince, Randall A

    2016-05-01

    Dalbavancin is a long acting, bactericidal lipoglycopeptide. Its in vitro activity was compared with that of vancomycin, daptomycin, linezolid, trimethoprim/sulfamethoxazole (TMP/SMX) and levofloxacin against 241 Gram-positive organisms isolated from cancer patients. The rank order of potency for the glycopeptides based on MIC90 (μg ml(-1)), that is, the concentration of antimicrobial agent required to inhibit 90% of isolates tested was dalbavancin (0.12 μg ml(-1))>daptomycin (1.0 μg ml(-1))>vancomycin (2.0 μg ml(-1)) for coagulase-negative staphylococci and Staphylococcus aureus isolates (including methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains). Dalbavancin had potent activity against staphylococcal isolates with vancomycin MICs⩾1.0 μg ml(-1). TMP/SMX also had potent activity against staphylococci including methicillin-resistant strains, whereas levofloxacin had moderate to poor anti-staphylococcal activity. Dalbavancin also exhibited more potent activity than vancomycin and daptomycin against Bacillus spp., Corynebacterium spp., Micrococcus spp. and various streptococci (including Streptococcus pneumoniae, viridans group streptococci (VGS), beta-hemolytic streptococci and gamma-hemolytic streptococci). MBC determinations showed that dalbavancin had potent bactericidal activity against MRSA with no tolerance being detected. These data suggest that dalbavancin may be considered as an alternative to vancomycin, especially in institutions wherein a substantial proportion of infections are caused by organisms with vancomycin MICs⩾1.0 μg ml(-1). PMID:26626876

  3. Enediyne compounds - new promises in anticancer therapy.

    Science.gov (United States)

    Gredicak, Matija; Jerić, Ivanka

    2007-06-01

    Scientists of all kinds have long been intrigued by the nature, action and potential of natural toxins that possess exceptional antibacterial and anticancer activities. These compounds, named enediynes, are among the most effective chemotherapeutic agents known. Often compared with intelligent weapons, due to the unique structure and sophisticated mechanism by which they destroy double-helical DNA, enediyne antibiotics are nowadays the most promising leaders in the anticancer therapy. Apart from their diversity, enediyne compounds share some structural and functional similarities. One fragment of a structure is responsible for the recognition and transport, another part acts as molecular trigger while the third, reactive enediyne unit, undergoes Bergman cycloaromatization and causes DNA breakage. Members of the enediyne family are already in clinical use to treat various cancers, but more general use is limited by their complex structure, which makes them formidable targets for synthetic chemists. There are three main approaches in the design of new enediyne-related compounds: improvement of enediyne >warheadsenediynes, their mode of action and efforts undertaken to design artificial enediyne-related DNA cleaving agents. PMID:17507311

  4. Pathogenicity of local isolate virus BHV-1 as the aetiological agent of Infectious Bovine Rhinotracheitis in Bali Cattle

    OpenAIRE

    Rini I Damayanti; Sudarisman

    2005-01-01

    Infectious Bovine Rhinotracheitis is a disease of cattle characterised by clinical signs of the upper respiratory tract, reproductive tract and nervous system. A study to define the pathogenicity of four BHV-1 local isolates has been conducted. Fourteen Bali cattle that were free of BHV-1 has been selected and divided into four treatment groups. Each group of three was infected with virus isolate I, II, III and IV respectively with approximately a dose of 108TCID50 /10 ml and two cattle were ...

  5. In vitro and in vivo Methods for Anticancer Activity Evaluation and Some Indian Medicinal Plants Possessing Anticancer Properties: An Overview

    Directory of Open Access Journals (Sweden)

    Sumitra Chanda

    2013-07-01

    Full Text Available Cancer is a major public health burden in both developed and developing countries. Anticancer activity is the effect of natural and synthetic or biological and chemical agents to reverse, suppress or prevent carcinogenic progression. Several synthetic agents are used to cure the disease but they have their toxicity and hence the research is going on to investigate the plant derived chemotherapeutic agents. Therefore an attempt has been made to review different in vitro and in vivo methods for estimating anticancer properties of natural products from medicinal plants. In this review, 50 anticancer medicinal plants of Indian origin belonging to 35 families are reported along with detailed information regarding part used, extract used, type of the model used, types of tested cancer cell lines, etc. These plants continue to be used against various types of tumours such as sarcoma, lymphoma, carcinoma and leukemia. All these plants are potential candidates for in vivo studies since they are showing good in vitro anticancer activity.

  6. Effect of Thiol-reducing Agents and Antioxidants on Sulfasalazine-induced Hepatic Injury in Normotermic Recirculating Isolated Perfused Rat Liver

    Science.gov (United States)

    Heidari, Reza; Esmailie, Neda; Azarpira, Negar; Najibi, Asma; Niknahad, Hossein

    2016-01-01

    Sulfasalzine is a widely administered drug against inflammatory-based disorders in human. However several cases of liver injury are associated with its administration. There is no stabilized safe protective agent against sulfasalazine-induced liver injury. Current investigation was designed to evaluate if N-acetylcysteine (NAC) and dithioteritol (DTT) as thiol reducing agents and/or vitamins C and E as antioxidants have any protective effects against sulfasalazine-induced hepatic injury in an ex vivo model of isolated rat liver. Rat liver was canulated and perfused via portal vein in a closed recirculating system. Different concentrations of sulfasalazine and/or thiol reductants and antioxidants were administered and markers of organ injury were monitored at different time intervals. It was found that 5 mM of sulfasalazine caused marked liver injury as judged by rise in liver perfusate level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (p < 0.05). A significant amount of lipid peroxidation and hepatic glutathione depletion were detected in drug-treated livers, accompanied with significant histopathological changes of the organ. Administration of NAC (500 μM), DTT (400 μM), Vitamin C (200 μM), or vitamin E (200 μM) significantly alleviated sulfasalazine-induced hepatic injury in isolated perfused rat liver. The data obtained from current investigation indicate potential therapeutic properties of thiol reductants and antioxidants against sulfasalazine-induced liver injury. PMID:27123164

  7. Effect of Thiol-reducing Agents and Antioxidants on Sulfasalazine-induced Hepatic Injury in Normotermic Recirculating Isolated Perfused Rat Liver.

    Science.gov (United States)

    Heidari, Reza; Esmailie, Neda; Azarpira, Negar; Najibi, Asma; Niknahad, Hossein

    2016-04-01

    Sulfasalzine is a widely administered drug against inflammatory-based disorders in human. However several cases of liver injury are associated with its administration. There is no stabilized safe protective agent against sulfasalazine-induced liver injury. Current investigation was designed to evaluate if N-acetylcysteine (NAC) and dithioteritol (DTT) as thiol reducing agents and/or vitamins C and E as antioxidants have any protective effects against sulfasalazine-induced hepatic injury in an ex vivo model of isolated rat liver. Rat liver was canulated and perfused via portal vein in a closed recirculating system. Different concentrations of sulfasalazine and/or thiol reductants and antioxidants were administered and markers of organ injury were monitored at different time intervals. It was found that 5 mM of sulfasalazine caused marked liver injury as judged by rise in liver perfusate level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (p Vitamin C (200 μM), or vitamin E (200 μM) significantly alleviated sulfasalazine-induced hepatic injury in isolated perfused rat liver. The data obtained from current investigation indicate potential therapeutic properties of thiol reductants and antioxidants against sulfasalazine-induced liver injury. PMID:27123164

  8. Tea nanoparticle, a safe and biocompatible nanocarrier, greatly potentiates the anticancer activity of doxorubicin.

    Science.gov (United States)

    Wang, Yi-Jun; Huang, Yujian; Anreddy, Nagaraju; Zhang, Guan-Nan; Zhang, Yun-Kai; Xie, Meina; Lin, Derrick; Yang, Dong-Hua; Zhang, Mingjun; Chen, Zhe-Sheng

    2016-02-01

    An infusion-dialysis based procedure has been developed as an approach to isolate organic nanoparticles from green tea. Tea nanoparticle (TNP) can effectively load doxorubicin (DOX) via electrostatic and hydrophobic interactions. We established an ABCB1 overexpressing tumor xenograft mouse model to investigate whether TNP can effectively deliver DOX into tumors and bypass the efflux function of the ABCB1 transporter, thereby increasing the intratumoral accumulation of DOX and potentiating the anticancer activity of DOX. MTT assays suggested that DOX-TNP showed higher cytotoxicity toward CCD-18Co, SW620 and SW620/Ad300 cells than DOX. Animal study revealed that DOX-TNP resulted in greater inhibitory effects on the growth of SW620 and SW620/Ad300 tumors than DOX. In pharmacokinetics study, DOX-TNP greatly increased the SW620 and SW620/Ad300 intratumoral concentrations of DOX. But DOX-TNP had no effect on the plasma concentrations of DOX. Furthermore, TNP is a safe nanocarrier with excellent biocompatibility and minimal toxicity. Ex vivo IHC analysis of SW620 and SW620/Ad300 tumor sections revealed evidence of prominent antitumor activity of DOX-TNP. In conclusion, our findings suggested that natural nanomaterials could be useful in combating multidrug resistance (MDR) in cancer cells and potentiating the anticancer activity of chemotherapeutic agents in cancer treatment. PMID:26716507

  9. Preparation of thermo and pH-responsive polymer@Au/Fe{sub 3}O{sub 4} core/shell nanoparticles as a carrier for delivery of anticancer agent

    Energy Technology Data Exchange (ETDEWEB)

    Ghorbani, Marjan [University of Tabriz, Laboratory of Polymer, Faculty of Chemistry (Iran, Islamic Republic of); Hamishehkar, Hamed, E-mail: hamishehkarh@tbzmed.ac.ir [Tabriz University of Medical Sciences, Drug Applied Research Center (Iran, Islamic Republic of); Arsalani, Naser; Entezami, Ali Akbar, E-mail: aentezami@tabrizu.ac.ir [University of Tabriz, Laboratory of Polymer, Faculty of Chemistry (Iran, Islamic Republic of)

    2015-07-15

    In this work, a thermo and pH-responsive poly-N-isopropylacrylamide-co-itaconic acid containing thiol side groups were successfully synthesized to prepare Doxorubicin-loaded polymer@Au/Fe{sub 3}O{sub 4} core/shell nanoparticles (DOX-NPs). Copolymer and NPs were fully characterized by FT-IR, HNMR, photo-correlation spectroscopy, SEM, X-ray diffraction, vibrating-sample magnetometer, thermal gravimetric analysis, and UV–Vis spectroscopy. The stimuli-responsive characteristics of NPs were evaluated by in vitro release study in simulated cancerous environment. The biocompatibility and cytotoxic properties of NPs and DOX-NPs are explored by MTT method. The prepared NPs with the size of 50 nm showed paramagnetic characteristics with suitable and stable dispersion at physiological medium and high loading capacity (up to 55 %) of DOX. DOX-NPs yielded a pH- and temperature-triggered release of entrapped drugs at tumor tissue environment (59 % of DOX release) compared to physiological condition (20 % of DOX release) during 48 h. In vitro cytotoxicity studies indicated that the NPs showed no cytotoxicity on A549 cells at different amounts after incubation for 72 h confirming its suitability as a drug carrier. DOX-NPs, on the other hand, caused an efficient anticancer performance as verified by MTT assay test. It was concluded that developed NPs by us in this study may open the possibilities for targeted delivery of DOX to the cancerous tissues.

  10. Distribution of contagious and environmental mastitis agents isolated from milk samples collected from clinically health buffalo cows between brazilian dry and rainy seasons of the year

    Directory of Open Access Journals (Sweden)

    R.P. Maia

    2010-02-01

    Full Text Available The present study was performed to evaluate the microbiological characteristics of clinically health quarters submitted to milking and also to observe the distribution of contagious and environmental agents between brazilian dry and rainy seasons of the year. During nine months 734 quarters from 37 buffalo cows were submitted monthly to udder inspection, palpation and strip cup test before milking. 734 asseptic milk samples were inoculated in 10% ovine blood agar and in MacConkey agar media, then incubated for 72 hours at 37oC. Among the 580 isolated microrganisms, 182 (31,38% were recovered from samples collected during the rainy season and 398 (68,62% from the dry season. In the rainy period the most prevalent agents were: bacteria from the genus Corynebacterium sp (53,30%, Staphylococcus sp (19,78% and Rhodococcus equi (13,74%. In the dry period, the commonest ones were: Corynebacterium sp (44,97%, Staphylococcus sp (18,84% and Micrococcus sp (9,55%. The results demonstrated that the methods used to select health quarters in brazilian dairy buffalo farms allow the transmission of contagious bacteria during both seasons of the year, maintaining Ital.J.Anim.Sci. vol. 6, (Suppl. 2, 896-899, 2007 897 VIII World Buffalo Congress agents known to cause mainly subclinical inflammatory reactions that compromise cronically the physiology and production of the mammary gland.

  11. From body art to anticancer activities: perspectives on medicinal properties of henna.

    Science.gov (United States)

    Pradhan, Rohan; Dandawate, Prasad; Vyas, Alok; Padhye, Subhash; Biersack, Bernhard; Schobert, Rainer; Ahmad, Aamir; Sarkar, Fazlul H

    2012-12-01

    Nature has been a rich source of therapeutic agents for thousands of years and an impressive number of modern drugs have been isolated from natural sources based on the uses of these plants in traditional medicine. Henna is one such plant commonly known as Persian Henna or Lawsonia inermis, a bushy, flowering tree, commonly found in Australia, Asia and along the Mediterranean coasts of Africa. Paste made from the leaves of Henna plant has been used since the Bronze Age to dye skin, hairs and fingernails especially at the times of festivals. In recent times henna paste has been used for body art paintings and designs in western countries. Despite such widespread use in dyeing and body art painting, Henna extracts and constituents possess numerous biological activities including antioxidant, anti-inflammatory, antibacterial and anticancer activities. The active coloring and biologically active principle of Henna is found to be Lawsone (2- hydroxy-1, 4-naphthoquinone) which can serve as a starting building block for synthesizing large number of therapeutically useful compounds including Atovaquone, Lapachol and Dichloroallyl lawsone which have been shown to possess potent anticancer activities. Some other analogs of Lawsone have been found to exhibit other beneficial biological properties such as antioxidant, anti-inflammatory, antitubercular and antimalarial. The ability of Lawsone to undergo the redox cycling and chelation of trace metal ions has been thought to be partially responsible for some of its biological activities. Despite such diverse biological properties and potent anticancer activities the compound has remained largely unexplored and hence in the present review we have summarized the chemistry and biological activities of Lawsone along with its analogs and metal complexes. PMID:23140289

  12. Lanostanoids from fungi: a group of potential anticancer compounds.

    Science.gov (United States)

    Ríos, José-Luis; Andújar, Isabel; Recio, María-Carmen; Giner, Rosa-María

    2012-11-26

    Lanostanes are a group of tetracyclic triterpenoids derived from lanosterol. They have relevant biological and pharmacological properties, such as their cytotoxic effects via induction of apoptosis. This review compiles the most relevant lanostanoids studied from 2000 to 2011, principally those isolated from Ganoderma lucidum and other related fungi, such as Poria cocos, Laetiporus sulphureus, Inonotus obliquus, Antrodia camphorata, Daedalea dickinsii, and Elfvingia applanata, which have great potential as anticancer agents because of their cytotoxic or apoptotic effects. The compounds were selected on the basis of their proapoptotic mechanisms, through their ability to modify transcriptional activities via nuclear factors or genes and the activation or inhibition of pro- or antiapoptotic proteins; studies based only on their cytotoxicity were excluded from this review in the absence of complementary studies on their mechanisms of action. A total of 81 compounds from Ganoderma lucidum and other species from this genus are included, as well as 96 compounds isolated from other fungi, principally Poria cocos. Some of these compounds were found to arrest the cell cycle in the G1 phase, increase levels of p53 and Bax, or inhibit the phosphorylation of Erk1/2 or the activation of NF-κB and AP-1. Other lanostanes have inhibitory effects on the growth of androgen prostate carcinoma through increasing the expression of p21, which activates the tumor suppressor protein p53, while other compounds have been shown to selectively inhibit topo II activity without affecting topo I. General considerations concerning the chemical structure-biological activities of these compounds are also discussed. PMID:23092389

  13. Suspension culture combined with chemotherapeutic agents for sorting of breast cancer stem cells

    International Nuclear Information System (INIS)

    Cancer stem cell (CSC) hypothesis has not been well demonstrated by the lack of the most convincing evidence concerning a single cell capable of giving rise to a tumor. The scarcity in quantity and improper approaches for isolation and purification of CSCs have become the major obstacles for great development in CSCs. Here we adopted suspension culture combined with anticancer regimens as a strategy for screening breast cancer stem cells (BrCSCs). BrCSCs could survive and be highly enriched in non-adherent suspension culture while chemotherapeutic agents could destroy most rapidly dividing cancer cells and spare relatively quiescent BrCSCs. TM40D murine breast cancer cells were cultured in serum-free medium. The expression of CD44+CD24- was measured by flow cytometry. Cells of passage 10 were treated in combination with anticancer agents pacilitaxel and epirubicin at different peak plasma concentrations for 24 hours, and then maintained under suspension culture. The rate of apoptosis was examined by flow cytometry with Annexin-V fluorescein isothiocyanate (FITC)/propidium iodide (PI) double staining method. Selected cells in different amounts were injected subcutaneously into BALB/C mice to observe tumor formation. Cells of passage 10 in suspension culture had the highest percentage of CD44+CD24- (about 77 percent). A single tumor cell in 0.35 PPC could generate tumors in 3 of 20 BALB/C mice. Suspension culture combined with anticancer regimens provides an effective means of isolating, culturing and purifying BrCSCs

  14. In vitro susceptibility of Staphylococcus aureus strains isolated from cows with subclinical mastitis to different antimicrobial agents

    OpenAIRE

    Behiry, Ayman El; Schlenker, Gerd; Szabo, Istvan; Roesler, Uwe

    2012-01-01

    Sensitivity to commercial teat dips (nonoxinol-9 iodine complex and chlorhexidine digluconate) of 56 Staphylococcus (S.) aureus strains isolated from quarter milk samples of various German dairy herds treated with different teat dipping schemes was investigated in this study. The minimum inhibitory concentration was determined using a broth macrodilution method according to the German Veterinary Association guidelines. The main objective of the current study was to induce in vitro resistance ...

  15. Câncer e agentes antineoplásicos ciclo-celular específicos e ciclo-celular não específicos que interagem com o DNA: uma introdução Cancer and cell cicle-specific and cell cicle nonspecific anticancer DNA-interactive agents: an introduction

    OpenAIRE

    Vera Lúcia Almeida; Andrei Leitão; Luisa del Carmen Barrett Reina; Carlos Alberto Montanari; Claudio Luis Donnici; Míriam Teresa Paz Lopes

    2005-01-01

    The chemotherapy agents against cancer may be classified as "cell cycle-specific" or "cell cycle-nonspecific". Nevertheless, several of them have their biological activity related to any kind of action on DNA such as: antimetabolic agents (DNA synthesis inhibition), inherently reactive agents (DNA alkylating electrophilic traps for macromolecular nucleophiles from DNA through inter-strand cross-linking - ISC - alkylation) and intercalating agents (drug-DNA interactions inherent to the binding...

  16. THE JOURNAL OF TROPICAL LIFE SCIENCE OPEN ACCESS Freely available online VOL. 5, NO. 2, pp. 88-91, May, 2015 Isolation of an Anti-Cancer Asperuloside from Hedyotis corymbosa L.

    OpenAIRE

    Nina Artanti; Muhammad Hanafi; Rina Andriyani; Vienna Saraswati; Zalinar Udin; Puspa D. Lotulung; Ken Ichi Fujita; Yoshinosuke Usuki

    2015-01-01

    Hedyotis corymbosa L., with local name rumput mutiara, is an anti-inflammatory, anti-cancer and hepatoprotective traditional medicine. The ethanol extract of H. corymbosa L. shows inhibitory activity to humanYMB-1 breast cancer cell line with an IC50 of 6.51 μg/mL. The methylene chloride fraction shows a potential cytotoxic activity with an IC50 of 2.75 μg/mL. To obtain a lead compound, the extract was further purified by column chromatography. A pure compound is obtained which shows inhibito...

  17. Molecular Characterization and Sequencing of a Gene Encoding Mannose Binding Protein in an Iranian Isolate of Acanthamoeba castellanii as a Major Agent of Acanthamoeba Keratitis

    Directory of Open Access Journals (Sweden)

    SH Farnia

    2008-07-01

    Full Text Available Background: Acanthamoeba castellanii is the important cause of amoebic keratitis in Iran. The key molecule in pathogenesis of Acanthamoeba keratitis is Mannose Binding Protein (MBP led to adhesion of amoeba to corneal epithelium. Subsequent to adhesion other cytopathic effects occur. The goal of this study was to identify the molecular characterization of a gene encoding MBP in an Iranian isolate of A.castellanii in order to pave the way for further investigations such as new therapeutic advances or immunization. Methods: A.castellanii was cultured on non nutrient agar. Extraction of DNA was performed by phenol-chloroform method. After designing a pair of primer for the gene encoding MBP, PCR analysis was performed. Finally, the PCR product has been sequenced and the result submitted to the gene data banks. Results: An MBP gene of 1081 nucleotides was sequenced. This fragment contained three introns and encodes a protein with 194 amino acids. Homology search by Blast program showed a significant homology with the MBP gene in gene data banks (96%. Besides, the identity of amino acids with the other MBPs in gene data banks was about 86%. Conclusion: We isolated and sequenced a gene fragment encoding MBP in an Iranian isolate of A.castellanii. Molecular characterization of this important gene is the first step in pursuing researches such as developing better therapeutic agents, immunization of population at risk or even developing a diagnostic tool by PCR techniques.

  18. In vitro antifungal activity of ME1111, a new topical agent for onychomycosis, against clinical isolates of dermatophytes.

    Science.gov (United States)

    Ghannoum, M; Isham, N; Long, L

    2015-09-01

    The treatment of onychomycosis has improved considerably over the past several decades following the introduction of the oral antifungals terbinafine and itraconazole. However, these oral agents suffer from certain disadvantages, including drug interactions and potential liver toxicity. Thus, there is a need for new topical agents that are effective against onychomycosis. ME1111 is a novel selective inhibitor of succinate dehydrogenase (complex II) of dermatophyte species, whose small molecular weight enhances its ability to penetrate the nail plate. In this study, we determined the antifungal activity of ME1111 against dermatophyte strains, most of which are known to cause nail infections, as measured by the MIC (n = 400) and the minimum fungicidal concentration (MFC) (n = 300). Additionally, we examined the potential for resistance development in dermatophytes (n = 4) following repeated exposure to ME1111. Our data show that the MIC90 of ME1111 against dermatophyte strains was 0.25 μg/ml, which was equivalent to that of the comparators amorolfine and ciclopirox (0.25 and 0.5 μg/ml, respectively). ME1111 was fungicidal at clinically achievable concentrations against dermatophytes, and its MFC90s against Trichophyton rubrum and Trichophyton mentagrophytes were 8 μg/ml, comparable to those of ciclopirox. Furthermore, ME1111, as well as ciclopirox, did not induce resistance in 4 dermatophytes tested. Our studies show that ME1111 possesses potent antifungal activity and suggest that it has low potential for the development of resistance in dermatophytes. PMID:26055386

  19. Non-cytotoxic antifungal agents: isolation and structures of gageopeptides A-D from a Bacillus strain 109GGC020.

    Science.gov (United States)

    Tareq, Fakir Shahidullah; Lee, Min Ah; Lee, Hyi-Seung; Lee, Yeon-Ju; Lee, Jong Seok; Hasan, Choudhury M; Islam, Md Tofazzal; Shin, Hee Jae

    2014-06-18

    Antifungal resistance and toxicity problems of conventional fungicides highlighted the requirement of search for new safe antifungal agents. To comply with the requirement, we discovered four new non-cytotoxic lipopeptides, gageopeptides A-D, 1-4, from a marine-derived bacterium Bacillus subtilis. The structures and stereochemistry of gageopeptides were determined by NMR data analysis and chemical means. Gageopeptides exhibited significant antifungal activities against pathogenic fungi Rhizoctonia solani, Botrytis cinerea, and Colletotrichum acutatum with minimum inhibitory concentration (MIC) values of 0.02-0.06 μM. In addition, these lipopeptides showed significant motility inhibition and lytic activities against zoospores of the late blight pathogen Phytophthora capsici. These compounds also showed potent antimicrobial activity against Gram positive and Gram negative bacteria with MIC values of 0.04-0.08 μM. However, gageopeptides A-D did not exhibit any cytotoxicity (GI50 > 25 μM) against cancer cell lines in sulforhodamine B (SRB), 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), and WST-1 ((4-[3-4-iodophenyl]-2-(4-nitrophenyl)-2H-5-tetrazolio)-1,3-benzene disulfonate)) assays, demonstrating that these compounds could be promising candidates for the development of non-cytotoxic antifungal agents. PMID:24857413

  20. Isolation of Serratia marcescens SR1 as a Source of Chitinase Having Potentiality of Using as a Biocontrol Agent

    OpenAIRE

    Parani, K.; Shetty, G. P.; Saha, B K

    2011-01-01

    Serratia marcescens, strain SR1 was isolated from the local soil of a cultivated farm and it was screened as potent strain for chitinase production. Maximum chitinase production (77.3 u Mh−1 100−1) was observed after 96 h of incubation period with pH 5.5 at 30°C under shake conditions (120 rpm). Compare to still flasks, shake culture with prawn fish colloidal chitin of 0.5% (w/v) concentration, showed a better enzyme yield. Crude enzyme showed antifungal activity against plant pathogens....

  1. Isolation and characterization of the hamster gadd153 gene. Activation of promoter activity by agents that damage DNA

    Energy Technology Data Exchange (ETDEWEB)

    Luethy, J.D.; Fargnoli, J.; Park, J.S.; Fornace, A.J. Jr.; Holbrook, N.J. (National Institute on Aging, Baltimore, MD (USA))

    1990-09-25

    A group of five cDNA clones, representing the gadd genes, were recently isolated from Chinese hamster ovary (CHO) cells as genes induced upon growth arrest and after DNA damage. We have isolated and characterized one of these genes, gadd153. The gene spans five kilobases and contains four exons. The 5'-flanking region of the gene, within 420 base pairs of the transcription initiation site, contains a number of cis elements associated with transcriptional regulation in other genes. These include a Hogness box, ATAAAA, an inverted GCCAAT box; seven SP1 transcription factor binding sites, and an AP-1 site. This region is rich in G + C content (greater than 70%) and contains an unusually long stretch of alternating CpG residues. The 800-base pair region immediately upstream of the transcription start site can drive expression of the bacterial chloramphenicol acetyltransferase (CAT) gene, but only in its endogenous orientation, in three different cell lines: HeLa, CHO, and Jurkat. The gadd153 promoter is strongly activated by methyl methanesulfonate, hydrogen peroxide, and UV irradiation, but not by growth arrest signals. This suggests that separate and very different regulatory pathways are involved in the induction of the gadd153 gene by growth cessation and DNA damage.

  2. In vitro susceptibility of Staphylococcus aureus strains isolated from cows with subclinical mastitis to different antimicrobial agents

    Science.gov (United States)

    Schlenker, Gerd; Szabo, Istvan; Roesler, Uwe

    2012-01-01

    Sensitivity to commercial teat dips (nonoxinol-9 iodine complex and chlorhexidine digluconate) of 56 Staphylococcus (S.) aureus strains isolated from quarter milk samples of various German dairy herds treated with different teat dipping schemes was investigated in this study. The minimum inhibitory concentration was determined using a broth macrodilution method according to the German Veterinary Association guidelines. The main objective of the current study was to induce in vitro resistance induction of S. aureus to chemical disinfectants. Ten different strains were repeatedly passed ten times in growth media with sub-lethal concentrations of disinfectants. Nine strains showed a significant reduction in susceptibility to the nonoxinol-9 iodine complex but only one strain developed resistance to chlorhexidine digluconate. Stability of the acquired resistance was observed in all S. aureus strains adapted to the nonoxinol-9 iodine complex and chlorhexidine digluconate. In contrast, simultaneous resistance to different antibiotics was not observed in any of the ten investigated S. aureus strains. However, the isolates exhibited a high degree of resistance to penicillin G. Based on these results, resistance of S. aureus to chemical disinfectants may be more likely to develop if the chemicals are used at concentrations lower than that required for an optimal biocidal effect. PMID:22705737

  3. [Surveillance of in vitro susceptibilities to levofloxacin and various antibacterial agents for 11,762 clinical isolates obtained from 69 centers in 2013].

    Science.gov (United States)

    Yamaguchi, Keizo; Tateda, Kazuhiro; Ohno, Akira; Ishii, Yoshikazu; Murakami, Hinako

    2016-02-01

    Antimicrobial susceptibility testing has been conducted continuously as postmarketing surveillance of levofloxacin (LVFX) since 1994. The present survey was undertaken to investigate in vitro susceptibilities of bacteria to 33 selected antibacterial agents, focusing on fluoroquinolones (FQs), using 11,762 clinical isolates for 19 species collected from 69 centers during 2013 in Japan. The common respiratory pathogens Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae continue to show a high susceptibility to FQs, while the percentage of macrolide-resistant S. pneumoniae was markedly increased to around 80%. With H. influenzae, the percentage of β-lactamase-negative ampicillin-resistant isolates had been increasing continuously from 2002, but no increase was observed from 2010 to 2013 (25.8% in 2002, 40.0% in 2004, 50.1% in 2007, 57.9% in 2010, and 57.1% in 2013). Most strains of Enterobacteriaceae showed a high susceptibility to FQs, but the isolation frequency of levofloxacin-resistant Escherichia coli including intermediate resistance was 34.4%, showing a continuous increase. Another Enterobacteriaceae member, Klebsiella pneumoniae, showed low resistance to FQs in contrast with E. coli. Regarding methicillin-resistant Staphylococcus aureus (MRSA), the percentage of FQ-susceptible isolates was low at 15.8-18.0%, with the exception of 55.3% susceptibility to sitafloxacin. On the other hand, methicillin-susceptible S. aureus (MSSA) isolates showed high susceptibility to FQs, at 87.0-99.3%. With Enterococcusfaecium, the percentage of FQ-susceptible isolates was 6.8-24.7%. The percentage of FQ-susceptible Pseudomonas aeruginosa was 83.4-89.3% among isolates derived from urinary tract infections (UTIs), while that from respiratory tract infections (RTIs) was 88.1-93.7%. This was summarized as susceptibility to FQs over 80% in both infections. A continuous decrease in FQ-resistant P. aeruginosa was noted, especially

  4. [Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1998). III. Secular changes in susceptibility].

    Science.gov (United States)

    Kumamoto, Y; Tsukamoto, T; Hirose, T; Matsukawa, M; Kunishima, Y; Matsuda, S; Sato, S; Ogiwara, M; Ishibashi, K; Fujime, M; Fujita, K; Shigeta, S; Watanabe, J; Igari, J; Yoshida, H; Imafuku, Y; Oguri, T; Murai, M; Yamaguchi, K; Matsumoto, T; Kashitani, F; Watanabe, K; Kobayashi, Y; Uchida, H; Ooe, H; Nishikawa, M; Kohno, S; Oka, T; Takano, Y; Miyagawa, Y; Miyazaki, Y; Izumikawa, K; Yamaguchi, T; Mochida, C; Furuhama, T

    2000-05-01

    Susceptibilities to various antimicrobial agents were examined for Enterococcus faecalis, Staphylococcus aureus, Echerichia coli, Klebsiella spp. and Pseudomonas aeruginosa that were isolated from patients with urinary tract infections (UTIs) in 9 hospitals during June 1998 to May 1999, and the results were compared with those obtained during the same period from 1990 to 1997 in uncomplicated UTIs and complicated UTIs. Among E. faecalis strains, those with low susceptibilities to almost drugs have increased in the latest period. All 5 S. aureus strains isolated from uncomplicated UTIs were the most susceptible to gentamicin (GM). Over 50% of S. aureus strains isolated from complicated UTIs were susceptible to GM, and on the contrary the resistant strains have increased with the MIC90 of 256 micrograms/ml or above. Among S. aureus strains isolated from complicated UTIs, those with low susceptibilities to arbekacin (ABK) have increased in the latest period compared to those during period of 1996-1997, and the MIC90s of them have changed into the lower state from 1 microgram/ml in 1996-1997 to 4 micrograms/ml in 1998. S. aureus strains have continued high susceptibilities to vancomycin (VCM). The susceptibilities to minocycline (MINO) of E. coli showed MIC90: 4 micrograms/ml in 1997, but those have returned in the latest period in uncomplicated UTIs. The MIC90s of ofloxacin (OFLX) to E. coli isolated from uncomplicated and complicated UTIs have been lower 2-3 classes in the latest period than those in 1997. Among Klebsiella spp. strains isolated from uncomplicated UTIs, those with low susceptibilities to almost cephems had increased in 1997, but few of them were detected in the latest study. The sensitive strains of P. aeruginosa to almost drugs have increased during the latest period. The MIC50s of cefozopran (CZOP) and OFLX against P. aeruginosa were the best in our history. The sensitive strains of P. aeruginosa to ceftazidime (CAZ) have increased and its

  5. Synthesis of some new heterocyclic compounds bearing a sulfonamide moiety and studying their combined anticancer effect with γ-radiation

    International Nuclear Information System (INIS)

    In search for new cytotoxic agents with improved anticancer profile, some new halogen-containing quinoline and pyrimido[4,5-b]quinoline derivatives bearing a free sulfonamide moiety were synthesized. All the newly synthesized target compounds were subjected to in vitro anticancer screening against human breast cancer cell line (MCF7). The most potent compounds, as concluded from the in vitro anticancer screening, were selected to be evaluated again for their in vitro anticancer activity in combination with radiation. Also, the newly synthesized compounds were docked in the active site of the carbonic anhydrase enzyme

  6. In vivo anticancer activity of vanillin semicarbazone

    Institute of Scientific and Technical Information of China (English)

    Shaikh M Mohsin Ali; M Abul Kalam Azad; Mele Jesmin; Shamim Ahsan; M Mijanur Rahman; Jahan Ara Khanam; M Nazrul Islam; Sha M Shahan Shahriar

    2012-01-01

    Objective:To evaluate the anticancer activity of vanillin semicarbazone (VSC) against Ehrlich ascites carcinoma (EAC) cells in Swiss albino mice. Methods:The compound VSC at three doses (5, 7.5 and 10 mg/kg i.p.) was administered into the intraperitoneal cavity of the EAC inoculated mice to observe its efficiency by studying the cell growth inhibition, reduction of tumour weight, enhancement of survival time as well as the changes in depleted hematological parameters. All such parameters were also studied with a known standard drug bleomycin at the dose of 0.3 mg/kg (i.p.). Results:Among the doses studied, 10 mg/kg (i.p.) was found to be quite comparable in potency to that of bleomycin at the dose of 0.3 mg/kg (i.p.). The host toxic effects of VSC was found to be negligible. Conclusions: It can be concluded that VSC can therefore be considered as potent anticancer agent.

  7. Conventional anticancer therapeutics and telomere maintenance mechanisms.

    Science.gov (United States)

    Uziel, Orit; Lahav, Meir

    2014-01-01

    The telomere-telomerase system has a unique role in the biology of cancer. Telomere maintenance, mostly affected by the up regulation of telomerase activity, is a prerequisite for perpetuation of malignant cells. This fundamental biologic feature defines telomere maintenance as an attractive therapeutic target for most types of cancer. This review summarizes some critical aspects of telomere biology with special emphasis on the connection to anticancer therapy. In particular, the effects on the telomere - telomerase system of conventional anticancer treatments, including various cytotoxic drugs, targeted biological agents and radiotherapy, and their possible combination with telomerase-directed therapy are discussed. Several potential problems, including side effects and complications inherent to perturbations of telomere biology in normal cells, are also highlighted. In spite of significant progress in this field, there are still several issues that have to be addressed and ultimately resolved in order to obtain a better characterization of the pros and cons of telomerase-directed therapies and, consequently, their clinical relevance. PMID:24975606

  8. Anticancer, Anti-Inflammatory, and Analgesic Activities of Synthesized 2-(Substituted phenoxy Acetamide Derivatives

    Directory of Open Access Journals (Sweden)

    Priyanka Rani

    2014-01-01

    Full Text Available The aphorism was to develop new chemical entities as potential anticancer, anti-inflammatory, and analgesic agents. The Leuckart synthetic pathway was utilized in development of novel series of 2-(substituted phenoxy-N-(1-phenylethylacetamide derivatives. The compounds containing 1-phenylethylamine as basic moiety attached to substituted phenols were assessed for their anticancer activity against MCF-7 (breast cancer, SK-N-SH (neuroblastoma, anti-inflammatory activity, and analgesic activity. These investigations revealed that synthesized products 3a–j with halogens on the aromatic ring favors as the anticancer and anti-inflammatory activity. Among all, compound 3c N-(1-(4-chlorophenylethyl-2-(4-nitrophenoxyacetamide exhibited anticancer, anti-inflammatory, and analgesic activities. In conclusion, 3c may have potential to be developed into a therapeutic agent.

  9. Anticancer, anti-inflammatory, and analgesic activities of synthesized 2-(substituted phenoxy) acetamide derivatives.

    Science.gov (United States)

    Rani, Priyanka; Pal, Dilipkumar; Hegde, Rahul Rama; Hashim, Syed Riaz

    2014-01-01

    The aphorism was to develop new chemical entities as potential anticancer, anti-inflammatory, and analgesic agents. The Leuckart synthetic pathway was utilized in development of novel series of 2-(substituted phenoxy)-N-(1-phenylethyl)acetamide derivatives. The compounds containing 1-phenylethylamine as basic moiety attached to substituted phenols were assessed for their anticancer activity against MCF-7 (breast cancer), SK-N-SH (neuroblastoma), anti-inflammatory activity, and analgesic activity. These investigations revealed that synthesized products 3a-j with halogens on the aromatic ring favors as the anticancer and anti-inflammatory activity. Among all, compound 3c N-(1-(4-chlorophenyl)ethyl)-2-(4-nitrophenoxy)acetamide exhibited anticancer, anti-inflammatory, and analgesic activities. In conclusion, 3c may have potential to be developed into a therapeutic agent. PMID:25197642

  10. First report of the emerging zoonotic agent Wohlfahrtiimonas chitiniclastica isolated from a retail frozen chicken in Rio de Janeiro, Brazil.

    Science.gov (United States)

    Matos, Jorge; Queiroga, Amanda Portela; de Oliveira Pedroza Bindi Dos Reis, Carlla Cristhina; Ribeiro, Rachel Leite; Teixeira, Lucia Martins; Albano, Rodolpho Mattos; de Freitas-Almeida, Angela Corrêa; Queiroz, Mara Lucia Penna

    2016-05-01

    Wohlfahrtiimonas chitiniclastica is an emerging zoonotic bacterium commensally living in larvae of particular flies. It has been associated with human and animal infections but never isolated from food. In the present study, a whole chicken carcass was rinsed in buffered peptone water which was then inoculated into BHI and the growth plated onto selective medium. Species identification was performed by MALDI-TOF MS. Those bacteria identified as W. chitiniclastica were subjected to 16S rRNA sequencing for confirmation and MEGA software was used to obtain their phylogenetic position. The findings of this study raise concerns regarding the abattoir, transport and stock practices of frozen meat carcasses and should be of interest with regard to microbiology, entomology and food production. PMID:26961699

  11. Ent-trachyloban-19-oic acid isolated from Iostephane heterophylla as a promising antibacterial agent against Streptococcus mutans biofilms.

    Science.gov (United States)

    Hernández, Dulce M; Díaz-Ruiz, Gloria; Rivero-Cruz, Blanca E; Bye, Robert A; Aguilar, María Isabel; Rivero-Cruz, J Fausto

    2012-04-01

    From the roots of Iostephane heterophylla, six known compounds, namely, ent-trachyloban-19-oic acid (1), the mixture of ent-kaur-16-en-19-oic acid (2) and ent-beyer-15-en-19-oic acid (3), xanthorrhizol (4), 16α-hydroxy-ent-kaurane (5) and 16α-hydroxy-ent-kaur-11-en-19-oic acid (6) were isolated using a bioassay-guided fractionation method. The known compounds (1-6) were identified by comparison of their spectroscopic data with reported values in the literature. In an attempt to increase the resultant antimicrobial activity of 1 and 4, a series of reactions was performed on ent-trachyloban-19-oic acid (1) and xanthorrhizol (4), to obtain derivatives 1a, 1b, and 4a-4d. All the isolated compounds (1-6) and the derivatives 1a, 1b, and 4a-4d were evaluated for their antimicrobial activity against two oral pathogens, Streptococcus mutans and Porphyromonas gingivalis associated with caries and periodontal disease, respectively. Compounds 1, 1b, 2+3, 4 and 4d inhibited the growth of S. mutans with concentrations ranging from 4.1 μg/mL to 70.5 μg/mL. No significant activity was found on P. gingivalis except for 4 with an MIC of 6.8 μg/mL. The ability of 1, 1b, 2+3, 4 and 4d to inhibit biofilm formation by S. mutans was evaluated. It was found that 1, 1b, 4 and 4d interfered with the establishment of S. mutans biofilms, inhibiting their development at 32.5, 125.0, 14.1 and 24.4 μg/mL, respectively. PMID:22245083

  12. Ethyl-2-amino-pyrrole-3-carboxylates are novel potent anticancer agents that affect tubulin polymerization, induce G2/M cell-cycle arrest, and effectively inhibit soft tissue cancer cell growth in vitro.

    Science.gov (United States)

    Boichuk, Sergei; Galembikova, Aigul; Zykova, Svetlana; Ramazanov, Bulat; Khusnutdinov, Ramil; Dunaev, Pavel; Khaibullina, Svetlana; Lombardi, Vincent

    2016-08-01

    Microtubules are known to be one of the most attractive and validated targets in cancer therapy. However, the clinical use of drugs that affect the dynamic state of microtubules has been hindered by chemoresistance and toxicity issues. Accordingly, the development of novel agents that target microtubules is needed. Here, we report the identification of novel compounds with pirrole and carboxylate structures: ethyl-2-amino-pyrrole-3-carboxylates (EAPCs) that provide potent cytotoxic activities against multiple soft tissue cancer cell lines in vitro. Using the MTS cell proliferation assay, we assessed the activity of EAPCs on various cancer cell lines including leiomyosarcoma SK-LMS-1, rhabdomyosarcoma RD, gastrointestinal stromal tumor GIST-T1, A-673 Ewing's sarcoma, and U-2 OS osteosarcoma. We found that in the majority of cases, two EAPC compounds (EAPC-20 and EAPC-24) considerably inhibited cancer cell proliferation in vitro. The growth-inhibitory effects of EAPC-20 and EAPC-24 were time and dose dependent. The molecular mechanisms of action of these compounds were because of the inhibition of tubulin polymerization and induction of a robust G2/M cell-cycle arrest, leading to considerable accumulation of tumor cells in the M-phase. Finally, EAPCs induced tumor cell death by apoptotic pathways. The above-mentioned effects were also observed in most soft tissue tumor cell lines and the gastrointestinal stromal tumor cell line investigated. Taken together, our data identify potent antitumor activity of EAPCs in vitro, thus providing a novel scaffold with which to develop potent chemotherapeutic agents for cancer therapy. PMID:27129079

  13. Effects of the encapsulation of usnic acid into liposomes and interactions with antituberculous agents against multidrug-resistant tuberculosis clinical isolates

    Directory of Open Access Journals (Sweden)

    Rafaela S Ferraz-Carvalho

    2016-01-01

    Full Text Available Mycobacterium tuberculosis (Mtb has acquired resistance and consequently the antibiotic therapeutic options available against this microorganism are limited. In this scenario, the use of usnic acid (UA, a natural compound, encapsulated into liposomes is proposed as a new approach in multidrug-resistant tuberculosis (MDR-TB therapy. Thus the aim of this study was to evaluate the effect of the encapsulation of UA into liposomes, as well as its combination with antituberculous agents such as rifampicin (RIF and isoniazid (INH against MDR-TB clinical isolates. The in vitro antimycobacterial activity of UA-loaded liposomes (UA-Lipo against MDR-TB was assessed by the microdilution method. The in vitro interaction of UA with antituberculous agents was carried out using checkerboard method. Minimal inhibitory concentration values were 31.25 and 0.98 µg/mL for UA and UA-Lipo, respectively. The results exhibited a synergistic interaction between RIF and UA [fractional inhibitory concentration index (FICI = 0.31] or UA-Lipo (FICI = 0.28. Regarding INH, the combination of UA or UA-Lipo revealed no marked effect (FICI = 1.30-2.50. The UA-Lipo may be used as a dosage form to improve the antimycobacterial activity of RIF, a first-line drug for the treatment of infections caused by Mtb.

  14. Antibacterial and Synergy of Berberines with Antibacterial Agents against Clinical Multi-Drug Resistant Isolates of Methicillin-Resistant Staphylococcus aureus (MRSA

    Directory of Open Access Journals (Sweden)

    Zhong-Qi Bian

    2012-08-01

    Full Text Available Antibacterial activity of berberine (Ber and 8-acetonyl-dihydroberberine (A-Ber alone and combined uses with antibacterial agents ampicillin (AMP, azithromycin (AZM, cefazolin (CFZ and levofloxacin (LEV was studied on 10 clinical isolates of SCCmec III type methicillin-resistant Staphylococcus aureus (MRSA. Susceptibility to each agent alone was tested using a broth microdilution method and the chequerboard and time-kill tests for the combined evaluations, respectively. The alone MICs/MBCs (mg/mL ranges were 32–128/64–256 (Ber and 32-128/128-512 (A-Ber. Significant synergies were observed for the Ber (A-Ber/AZM and Ber (A-Ber/LEV combinations against 90% of the tested MRSA strains, with fractional inhibitory concentration indices (FICIs values ranged  from 0.188 to 0.500. An additivity result was also observed for the Ber/AZM combination by time-kill curves. These results demonstrated for the first time that Ber and A-Ber enhanced the in vitro inhibitory efficacy of AZM and LEV to a same extent, which had potential for further investigation in combinatory therapeutic applications of patients infected with MRSA.

  15. Effects of the encapsulation of usnic acid into liposomes and interactions with antituberculous agents against multidrug-resistant tuberculosis clinical isolates.

    Science.gov (United States)

    Ferraz-Carvalho, Rafaela S; Pereira, Marcela A; Linhares, Leonardo A; Lira-Nogueira, Mariane Cb; Cavalcanti, Isabella Mf; Santos-Magalhães, Nereide S; Montenegro, Lílian Ml

    2016-05-01

    Mycobacterium tuberculosis (Mtb) has acquired resistance and consequently the antibiotic therapeutic options available against this microorganism are limited. In this scenario, the use of usnic acid (UA), a natural compound, encapsulated into liposomes is proposed as a new approach in multidrug-resistant tuberculosis (MDR-TB) therapy. Thus the aim of this study was to evaluate the effect of the encapsulation of UA into liposomes, as well as its combination with antituberculous agents such as rifampicin (RIF) and isoniazid (INH) against MDR-TB clinical isolates. The in vitro antimycobacterial activity of UA-loaded liposomes (UA-Lipo) against MDR-TB was assessed by the microdilution method. The in vitro interaction of UA with antituberculous agents was carried out using checkerboard method. Minimal inhibitory concentration values were 31.25 and 0.98 µg/mL for UA and UA-Lipo, respectively. The results exhibited a synergistic interaction between RIF and UA [fractional inhibitory concentration index (FICI) = 0.31] or UA-Lipo (FICI = 0.28). Regarding INH, the combination of UA or UA-Lipo revealed no marked effect (FICI = 1.30-2.50). The UA-Lipo may be used as a dosage form to improve the antimycobacterial activity of RIF, a first-line drug for the treatment of infections caused by Mtb. PMID:27143488

  16. Potentiating effect of ecofriendly synthesis of copper oxide nanoparticles using brown alga: antimicrobial and anticancer activities

    Indian Academy of Sciences (India)

    SRI VISHNU PRIYA RAMASWAMY; S NARENDHRAN; RAJESHWARI SIVARAJ

    2016-04-01

    This study reports the in vitro antimicrobial and anticancer activities of biologically synthesized copper nanoparticles. The antimicrobial activity of green synthesized copper oxide nanoparticles was assessed by well diffusion method. The anticancer activity of brown algae-mediated copper oxide nanoparticles was determined by MTT assay against the cell line (MCF-7). Maximum activity was observed with Pseudomonas aeruginosa and Aspergillus niger. Effective growth inhibition of cells was observed to be more than 93% in antibacterial activity. Thus, the results of the present study indicates that biologically synthesized copper nanoparticles can be used for several diseases, however, it necessitates clinical studies to ascertain their potential as antimicrobial and anticancer agents.

  17. In vivo Anticancer Activities of Benzophenone Semicarbazone against Ehrlich Ascites Carcinoma Cells in Swiss Albino Mice

    International Nuclear Information System (INIS)

    Benzophenone semicarbazone (BSC) was synthesized and characterized to identify compounds with anticancer activities. Anticancer activities were studied against Ehrlich Ascites Carcinoma (EAC) cells in Swiss albino mice by monitoring parameters such as tumor weight measurement, survival time of tumor bearing mice, tumor cell growth inhibition, and so on. Some hematological parameters, such as red blood cells, white blood cells, and hemoglobin content, were also measured. The results showed that BSC has a positive effect against EAC cells. An assessment was conducted by comparing these results with those obtained using the standard drug bleomycin. The BSC compound can be considered as a potent anticancer agent

  18. Recent Advances in chemistry and pharmacology of 2-methoxyestradiol: An anticancer investigational drug.

    Science.gov (United States)

    Kumar, B Sathish; Raghuvanshi, Dushyant Singh; Hasanain, Mohammad; Alam, Sarfaraz; Sarkar, Jayanta; Mitra, Kalyan; Khan, Feroz; Negi, Arvind S

    2016-06-01

    2-Methoxyestradiol (2ME2), an estrogen hormone metabolite is a potential cancer chemotherapeutic agent. Presently, it is an investigational drug under various phases of clinical trials alone or in combination therapy. Its anticancer activity has been attributed to its antitubulin, antiangiogenic, pro-apoptotic and ROS induction properties. This anticancer drug candidate has been explored extensively in last twenty years for its detailed chemistry and pharmacology. Present review is an update of its chemistry and biological activity. It also extends an assessment of potential of 2ME2 and its analogues as possible anticancer drug in future. PMID:27020471

  19. RECENT CHEMICAL ADVANCEMENTS OF PYRAZOLE MOIETY IN ANTICANCER THERAPY

    OpenAIRE

    Amrita Verma*; Suman Sharma; Rajani Chauhan

    2016-01-01

    Pyrazole moiety is one of the main scaffold for many anticancer drug candidates.Many pyrazole derivatives have been synthesized which shows their activity against different leukemia cell line, non-small cell lung cancer, colon cancer, prostate cancer, CNS cancer, renal cancer, breast cancer, ovarian cancer and cervix cancer cell line. Literature survey revealed that they have been implemented as antitumor, antileukemic and antiproliferative agent beside their capability to inhibit different t...

  20. Marine Invertebrate Metabolites with Anticancer Activities: Solutions to the “Supply Problem”

    OpenAIRE

    Gomes, Nelson G. M.; Ramesh Dasari; Sunena Chandra; Robert Kiss; Alexander Kornienko

    2016-01-01

    Marine invertebrates provide a rich source of metabolites with anticancer activities and several marine-derived agents have been approved for the treatment of cancer. However, the limited supply of promising anticancer metabolites from their natural sources is a major hurdle to their preclinical and clinical development. Thus, the lack of a sustainable large-scale supply has been an important challenge facing chemists and biologists involved in marine-based drug discovery. In the current revi...