Novel vitamin D compounds and skin cancer prevention

OpenAIRE

Tongkao-on, Wannit; Gordon-Thomson, Clare; Dixon, Katie M.; Song, Eric J.; Luu, Tan; Carter, Sally E.; Sequeira, Vanessa B.; Reeve, Vivienne E.; Mason, Rebecca S.

2013-01-01

As skin cancer is one of the most costly health issues in many countries, particularly in Australia, the possibility that vitamin D compounds might contribute to prevention of this disease is becoming increasingly more attractive to researchers and health communities. In this article, important epidemiologic, mechanistic and experimental data supporting the chemopreventive potential of several vitamin D-related compounds are explored. Evidence of photoprotection by the active hormone, 1α,25di...

Thioredoxin 1 modulates apoptosis induced by bioactive compounds in prostate cancer cells

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Aida Rodriguez-Garcia

2017-08-01

Full Text Available Accumulating evidence suggests that natural bioactive compounds, alone or in combination with traditional chemotherapeutic agents, could be used as potential therapies to fight cancer. In this study, we employed four natural bioactive compounds (curcumin, resveratrol, melatonin, and silibinin and studied their role in redox control and ability to promote apoptosis in androgen sensitive and insensitive prostate cancer cells. Here is shown that curcumin and resveratrol promote ROS production and induce apoptosis in LNCaP and PC-3. An increase in reactive species is a trigger event in curcumin-induced apoptosis and a consequence of resveratrol effects on other pathways within these cells. Moreover, here we demonstrated that these four compounds affect differently one of the main intracellular redox regulator, the thioredoxin system. Exposure to curcumin and resveratrol promoted TRX1 oxidation and altered its subcellular location. Furthermore, resveratrol diminished TRX1 levels in PC-3 cells and increased the expression of its inhibitor TXNIP. Conversly, melatonin and silibinin only worked as cytostatic agents, reducing ROS levels and showing preventive effects against TRX oxidation. All together, this work explores the effect of compounds currently tested as chemo-preventive agents in prostate cancer therapy, on the TRX1 redox state and function. Our work shows the importance that the TRX system might have within the differences found in their mechanisms of action. These bioactive compounds trigger different responses and affect ROS production and redox systems in prostate cancer cells, suggesting the key role that redox-related pathways might play in processes like differentiation or survival in prostate cancer. Keywords: Thioredoxin, Thioredoxin reductase, TXNIP, Prostate cancer, Redox signaling, Apoptosis

Dihydrochalcone Compounds Isolated from Crabapple Leaves Showed Anticancer Effects on Human Cancer Cell Lines

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Xiaoxiao Qin

2015-11-01

Full Text Available Seven dihydrochalcone compounds were isolated from the leaves of Malus crabapples, cv. “Radiant”, and their chemical structures were elucidated by UV, IR, ESI-MS, 1H-NMR and 13C-NMR analyses. These compounds, which include trilobatin (A1, phloretin (A2, 3-hydroxyphloretin (A3, phloretin rutinoside (A4, phlorizin (A5, 6′′-O-coumaroyl-4′-O-glucopyranosylphloretin (A6, and 3′′′-methoxy-6′′-O-feruloy-4′-O-glucopyranosyl-phloretin (A7, all belong to the phloretin class and its derivatives. Compounds A6 and A7 are two new rare dihydrochalcone compounds. The results of a MTT cancer cell growth inhibition assay demonstrated that phloretin and these derivatives showed significant positive anticancer activities against several human cancer cell lines, including the A549 human lung cancer cell line, Bel 7402 liver cancer cell line, HepG2 human ileocecal cancer cell line, and HT-29 human colon cancer cell line. A7 had significant effects on all cancer cell lines, suggesting potential applications for phloretin and its derivatives. Adding a methoxyl group to phloretin dramatically increases phloretin’s anticancer activity.

NPACT: Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database.

Science.gov (United States)

Mangal, Manu; Sagar, Parul; Singh, Harinder; Raghava, Gajendra P S; Agarwal, Subhash M

2013-01-01

Plant-derived molecules have been highly valued by biomedical researchers and pharmaceutical companies for developing drugs, as they are thought to be optimized during evolution. Therefore, we have collected and compiled a central resource Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database (NPACT, http://crdd.osdd.net/raghava/npact/) that gathers the information related to experimentally validated plant-derived natural compounds exhibiting anti-cancerous activity (in vitro and in vivo), to complement the other databases. It currently contains 1574 compound entries, and each record provides information on their structure, manually curated published data on in vitro and in vivo experiments along with reference for users referral, inhibitory values (IC(50)/ED(50)/EC(50)/GI(50)), properties (physical, elemental and topological), cancer types, cell lines, protein targets, commercial suppliers and drug likeness of compounds. NPACT can easily be browsed or queried using various options, and an online similarity tool has also been made available. Further, to facilitate retrieval of existing data, each record is hyperlinked to similar databases like SuperNatural, Herbal Ingredients' Targets, Comparative Toxicogenomics Database, PubChem and NCI-60 GI(50) data.

NPACT: Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database

Science.gov (United States)

Mangal, Manu; Sagar, Parul; Singh, Harinder; Raghava, Gajendra P. S.; Agarwal, Subhash M.

2013-01-01

Plant-derived molecules have been highly valued by biomedical researchers and pharmaceutical companies for developing drugs, as they are thought to be optimized during evolution. Therefore, we have collected and compiled a central resource Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database (NPACT, http://crdd.osdd.net/raghava/npact/) that gathers the information related to experimentally validated plant-derived natural compounds exhibiting anti-cancerous activity (in vitro and in vivo), to complement the other databases. It currently contains 1574 compound entries, and each record provides information on their structure, manually curated published data on in vitro and in vivo experiments along with reference for users referral, inhibitory values (IC50/ED50/EC50/GI50), properties (physical, elemental and topological), cancer types, cell lines, protein targets, commercial suppliers and drug likeness of compounds. NPACT can easily be browsed or queried using various options, and an online similarity tool has also been made available. Further, to facilitate retrieval of existing data, each record is hyperlinked to similar databases like SuperNatural, Herbal Ingredients’ Targets, Comparative Toxicogenomics Database, PubChem and NCI-60 GI50 data. PMID:23203877

Structure and Potential Cellular Targets of HAMLET-like Anti-Cancer Compounds made from Milk Components.

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Rath, Emma M; Duff, Anthony P; Håkansson, Anders P; Vacher, Catherine S; Liu, Guo Jun; Knott, Robert B; Church, William Bret

2015-01-01

The HAMLET family of compounds (Human Alpha-lactalbumin Made Lethal to Tumours) was discovered during studies on the properties of human milk, and is a class of protein-lipid complexes having broad spectrum anti-cancer, and some specific anti-bacterial properties. The structure of HAMLET-like compounds consists of an aggregation of partially unfolded protein making up the majority of the compound's mass, with fatty acid molecules bound in the hydrophobic core. This is a novel protein-lipid structure and has only recently been derived by small-angle X-ray scattering analysis. The structure is the basis of a novel cytotoxicity mechanism responsible for anti-cancer activity to all of the around 50 different cancer cell types for which the HAMLET family has been trialled. Multiple cytotoxic mechanisms have been hypothesised for the HAMLET-like compounds, but it is not yet clear which of those are the initiating cytotoxic mechanism(s) and which are subsequent activities triggered by the initiating mechanism(s). In addition to the studies into the structure of these compounds, this review presents the state of knowledge of the anti-cancer aspects of HAMLET-like compounds, the HAMLET-induced cytotoxic activities to cancer and non-cancer cells, and the several prospective cell membrane and intracellular targets of the HAMLET family. The emerging picture is that HAMLET-like compounds initiate their cytotoxic effects on what may be a cancer-specific target in the cell membrane that has yet to be identified. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Challenges of pin-point landing for planetary landing: the LION absolute vision-based navigation approach and experimental results

OpenAIRE

Voirin, Thomas; Delaune, Jeff; Le Besnerais, Guy; Farges, Jean Loup; Bourdarias, Clément; Krüger, Hans

2013-01-01

After ExoMars in 2016 and 2018, future ESA missions to Mars, the Moon, or asteroids will require safe and pinpoint precision landing capabilities, with for example a specified accuracy of typically 100 m at touchdown for a Moon landing. The safe landing requirement can be met thanks to state-of-the-art Terrain-Relative Navigation (TRN) sensors such as Wide-Field-of-View vision-based navigation cameras (VBNC), with appropriate hazard detection and avoidance algorithms. To reach the pinpoint pr...

HUBBLE PINPOINTS WHITE DWARFS IN GLOBULAR CLUSTER

Science.gov (United States)

2002-01-01

Peering deep inside a cluster of several hundred thousand stars, NASA's Hubble Space Telescope uncovered the oldest burned-out stars in our Milky Way Galaxy. Located in the globular cluster M4, these small, dying stars - called white dwarfs - are giving astronomers a fresh reading on one of the biggest questions in astronomy: How old is the universe? The ancient white dwarfs in M4 are about 12 to 13 billion years old. After accounting for the time it took the cluster to form after the big bang, astronomers found that the age of the white dwarfs agrees with previous estimates for the universe's age. In the top panel, a ground-based observatory snapped a panoramic view of the entire cluster, which contains several hundred thousand stars within a volume of 10 to 30 light-years across. The Kitt Peak National Observatory's 0.9-meter telescope took this picture in March 1995. The box at left indicates the region observed by the Hubble telescope. The Hubble telescope studied a small region of the cluster. A section of that region is seen in the picture at bottom left. A sampling of an even smaller region is shown at bottom right. This region is only about one light-year across. In this smaller region, Hubble pinpointed a number of faint white dwarfs. The blue circles pinpoint the dwarfs. It took nearly eight days of exposure time over a 67-day period to find these extremely faint stars. Globular clusters are among the oldest clusters of stars in the universe. The faintest and coolest white dwarfs within globular clusters can yield a globular cluster's age. Earlier Hubble observations showed that the first stars formed less than 1 billion years after the universe's birth in the big bang. So, finding the oldest stars puts astronomers within arm's reach of the universe's age. M4 is 7,000 light-years away in the constellation Scorpius. Hubble's Wide Field and Planetary Camera 2 made the observations from January through April 2001. These optical observations were combined to

Subtype and pathway specific responses to anticancer compounds in breast cancer.

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Heiser, Laura M; Sadanandam, Anguraj; Kuo, Wen-Lin; Benz, Stephen C; Goldstein, Theodore C; Ng, Sam; Gibb, William J; Wang, Nicholas J; Ziyad, Safiyyah; Tong, Frances; Bayani, Nora; Hu, Zhi; Billig, Jessica I; Dueregger, Andrea; Lewis, Sophia; Jakkula, Lakshmi; Korkola, James E; Durinck, Steffen; Pepin, François; Guan, Yinghui; Purdom, Elizabeth; Neuvial, Pierre; Bengtsson, Henrik; Wood, Kenneth W; Smith, Peter G; Vassilev, Lyubomir T; Hennessy, Bryan T; Greshock, Joel; Bachman, Kurtis E; Hardwicke, Mary Ann; Park, John W; Marton, Laurence J; Wolf, Denise M; Collisson, Eric A; Neve, Richard M; Mills, Gordon B; Speed, Terence P; Feiler, Heidi S; Wooster, Richard F; Haussler, David; Stuart, Joshua M; Gray, Joe W; Spellman, Paul T

2012-02-21

Breast cancers are comprised of molecularly distinct subtypes that may respond differently to pathway-targeted therapies now under development. Collections of breast cancer cell lines mirror many of the molecular subtypes and pathways found in tumors, suggesting that treatment of cell lines with candidate therapeutic compounds can guide identification of associations between molecular subtypes, pathways, and drug response. In a test of 77 therapeutic compounds, nearly all drugs showed differential responses across these cell lines, and approximately one third showed subtype-, pathway-, and/or genomic aberration-specific responses. These observations suggest mechanisms of response and resistance and may inform efforts to develop molecular assays that predict clinical response.

MOLECULAR DOCKING OF COMPOUNDS FROM Chaetomium Sp. AGAINST HUMAN ESTROGEN RECEPTOR ALPHA IN SEARCHING ANTI BREAST CANCER

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Maywan Hariono

2016-05-01

Full Text Available A study on molecular docking-based virtual screening has been conducted to select virtual hit of compounds, reported its existence in fungal endophytes of Chaetomium sp. as cytotoxic agent of breast cancer. The ligands were docked into Human Estrogen Receptor alpha (HERa as the protein which regulates the breast cancer growth via estradiol-estrogen receptor binding intervention. The results showed that two compounds bearing xanthone and two compounds bearing benzonaphtyridinedione scaffolds were selected as virtual hit ligands for HERa leading to the conclusion that these compounds were good to be developed as anti breast cancer.

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

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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 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

Urinary Volatile Organic Compounds for the Detection of Prostate Cancer.

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Tanzeela Khalid

Full Text Available The aim of this work was to investigate volatile organic compounds (VOCs emanating from urine samples to determine whether they can be used to classify samples into those from prostate cancer and non-cancer groups. Participants were men referred for a trans-rectal ultrasound-guided prostate biopsy because of an elevated prostate specific antigen (PSA level or abnormal findings on digital rectal examination. Urine samples were collected from patients with prostate cancer (n = 59 and cancer-free controls (n = 43, on the day of their biopsy, prior to their procedure. VOCs from the headspace of basified urine samples were extracted using solid-phase micro-extraction and analysed by gas chromatography/mass spectrometry. Classifiers were developed using Random Forest (RF and Linear Discriminant Analysis (LDA classification techniques. PSA alone had an accuracy of 62-64% in these samples. A model based on 4 VOCs, 2,6-dimethyl-7-octen-2-ol, pentanal, 3-octanone, and 2-octanone, was marginally more accurate 63-65%. When combined, PSA level and these four VOCs had mean accuracies of 74% and 65%, using RF and LDA, respectively. With repeated double cross-validation, the mean accuracies fell to 71% and 65%, using RF and LDA, respectively. Results from VOC profiling of urine headspace are encouraging and suggest that there are other metabolomic avenues worth exploring which could help improve the stratification of men at risk of prostate cancer. This study also adds to our knowledge on the profile of compounds found in basified urine, from controls and cancer patients, which is useful information for future studies comparing the urine from patients with other disease states.

Gold(III) bis(thiosemicarbazonate) compounds in breast cancer cells: Cytotoxicity and thioredoxin reductase targeting.

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Rodríguez-Fanjul, Vanessa; López-Torres, Elena; Mendiola, M Antonia; Pizarro, Ana María

2018-03-25

Gold(III) compounds have received increasing attention in cancer research. Three gold complexes of general formula [Au III L]Cl, where L is benzil bis(thiosemicarbazonate), compound 1, benzil bis(4-methyl-3-thiosemicarbazonate), compound 2, or benzil bis(4-cyclohexyl-3-thiosemicarbazonate), compound 3, have been synthesized and fully characterized, including the X-ray crystal structure of compound 3, confirming square-planar geometry around the gold(III) centre. Compound 1 showed moderate cytotoxicity and accumulation in MCF7 breast cancer cells but did not inhibit thioredoxin reductase (TrxR) activity and did not induce reactive oxygen species (ROS) production. Compound 2, the least cytotoxic, was found to be capable of modestly inhibiting TrxR activity and produced low levels of ROS in the MCF7 cell line. The most cytotoxic compound, 3, had the highest cellular accumulation and its distribution pattern showed a clear preference for the cytosol and mitochondria of MCF7 cells. It readily hampered intracellular TrxR activity leading to a dramatic alteration of the cellular redox state and to the induction of cell death. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Effect of compound radix sophorae flavescentis injection combined with Xiaoyao pill on breast cancer

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Xiao-Li Li

2016-12-01

Full Text Available Objective: To investigate the influence of compound radix sophorae flavescentis injection and Xiaoyao pill combined therapy on tumor markers, cytokines and lymphocyte subpopulations of breast cancer patients, thus provide relevant assistance on clinical therapy for breast cancer patients. Methods: A total of 170 breast cancer patients treated in our hospital were selected and divided to be the observe group and control group at random, 85 cases for each group. For patients in control group, AC chemotherapeutic project was utilized, and for patients in observe group, compound radix sophorae flavescentis injection and Xiaoyao pill combined therapy were provided on the basis of AC chemotherapy. Tumor markers, cytokines and lymphocyte subpopulations of breast cancer patients in each group were detected before and after therapy. Results: Comparison of tumor markers, cytokines and lymphocyte subpopulations levels between the two groups of breast cancer patients before therapy showed no statistical significant difference (P>0.05. Compared with prior therapy, the tumor markers (CA153, CEA and CYRA21-1, CD8+ and cytokines (IL-4, IL-6 and IL-10 on both the two groups of breast cancer patients were dramatically decreased, while lymphocyte subpopulations (CD3+ , CD4+ , CD4+ /CD8+ , IFN-γ and IL-2 were significantly increased (P<0.05. Conclusions: Compound radix sophorae flavescentis injection and Xiaoyao pill combined therapy can significantly improve the tumor markers, cytokines and lymphocyte subpopulations of the breast cancer patients. It is of vital clinical significance for treatment on breast cancer patients.

Synthesis and anti-lung cancer activity of a novel arsenomolybdate compound

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Zhu, Tian-Tian; Wang, Juan; Chen, Song-Hu

2017-12-01

The new compound based on Wells-Dawson-type arsenomolybdate: [{Cu10(pz)11Cl4}{As2IIIAs2VMo6VMo12VIO62}]·H2O (1) has been hydrothermally synthesized and characterized by single-crystal X-ray diffraction analysis, X-ray powder diffraction (XRPD), XPS spectroscopy and thermogravimetric analysis (TG). Compound 1 is consisted of two As caps Wells-dawson-type arsenomolybdate and {Cu10(py)11} complexes by chloride bridge. In addition, the antitumor effects of the title compound 1 were studied on three human lung cancer cells (A549, SK-LU-1 and SW1573). The results showed that compared with the positive reference drug carboplatin, compound 1 displayed efficient antitumor activity.

Differences in serum concentrations of organochlorine compounds by occupational social class in pancreatic cancer

International Nuclear Information System (INIS)

Porta, Miquel; Bosch de Basea, Magda; Benavides, Fernando G.; Lopez, Tomas; Fernandez, Esteve; Marco, Esther; Alguacil, Juan; Grimalt, Joan O.; Puigdomenech, Elisa

2008-01-01

Background: The relationships between social factors and body concentrations of environmental chemical agents are unknown in many human populations. Some chemical compounds may play an etiopathogenic role in pancreatic cancer. Objective: To analyze the relationships between occupational social class and serum concentrations of seven selected organochlorine compounds (OCs) in exocrine pancreatic cancer: dichlorodiphenyltrichloroethane (p,p'-DDT), dichlorodiphenyldichloroethene (p,p'-DDE), 3 polychlorinated biphenyls (PCBs), hexachlorobenzene, and β-hexachlorocyclohexane. Methods: Incident cases of exocrine pancreatic cancer were prospectively identified, and interviewed face-to-face during hospital admission (n=135). Serum concentrations of OCs were analyzed by high-resolution gas chromatography with electron-capture detection. Social class was classified according to occupation. Results: Multivariate-adjusted concentrations of all seven compounds were higher in occupational social classes IV-V (the less affluent) than in classes I-II; they were higher as well in class III than in classes I-II for four compounds. Concentrations of six OCs were higher in manual workers than in non-manual workers (p<0.05 for PCBs). Social class explained statistically between 3.7% and 5.7% of the variability in concentrations of PCBs, and 2% or less variability in the other OCs. Conclusions: Concentrations of most OCs were higher in the less affluent occupational social classes. In pancreatic cancer the putative causal role of these persistent organic pollutants may not be independent of social class. There is a need to integrate evidence on the contribution of different social processes and environmental chemical exposures to the etiology of pancreatic and other cancers

Correction of measured Gamma-Knife output factors for angular dependence of diode detectors and PinPoint ionization chamber.

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Hršak, Hrvoje; Majer, Marija; Grego, Timor; Bibić, Juraj; Heinrich, Zdravko

2014-12-01

Dosimetry for Gamma-Knife requires detectors with high spatial resolution and minimal angular dependence of response. Angular dependence and end effect time for p-type silicon detectors (PTW Diode P and Diode E) and PTW PinPoint ionization chamber were measured with Gamma-Knife beams. Weighted angular dependence correction factors were calculated for each detector. The Gamma-Knife output factors were corrected for angular dependence and end effect time. For Gamma-Knife beams angle range of 84°-54°. Diode P shows considerable angular dependence of 9% and 8% for the 18 mm and 14, 8, 4 mm collimator, respectively. For Diode E this dependence is about 4% for all collimators. PinPoint ionization chamber shows angular dependence of less than 3% for 18, 14 and 8 mm helmet and 10% for 4 mm collimator due to volumetric averaging effect in a small photon beam. Corrected output factors for 14 mm helmet are in very good agreement (within ±0.3%) with published data and values recommended by vendor (Elekta AB, Stockholm, Sweden). For the 8 mm collimator diodes are still in good agreement with recommended values (within ±0.6%), while PinPoint gives 3% less value. For the 4 mm helmet Diodes P and E show over-response of 2.8% and 1.8%, respectively. For PinPoint chamber output factor of 4 mm collimator is 25% lower than Elekta value which is generally not consequence of angular dependence, but of volumetric averaging effect and lack of lateral electronic equilibrium. Diodes P and E represent good choice for Gamma-Knife dosimetry. Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Compound K induced apoptosis via endoplasmic reticulum Ca2+ release through ryanodine receptor in human lung cancer cells

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Dong-Hyun Shin

2018-04-01

Full Text Available Background: Extended endoplasmic reticulum (ER stress may initiate apoptotic pathways in cancer cells, and ER stress has been reported to possibly increase tumor death in cancer therapy. We previously reported that caspase-8 played an important role in compound K-induced apoptosis via activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome c release, and caspase-9 activation in HL-60 human leukemia cells. The mechanisms leading to apoptosis in A549 and SK-MES-1 human lung cancer cells and the role of ER stress have not yet been understood. Methods: The apoptotic effects of compound K were analyzed using flow cytometry, and the changes in protein levels were determined using Western blot analysis. The intracellular calcium levels were monitored by staining with Fura-2/AM and Fluo-3/AM. Results: Compound K-induced ER stress was confirmed through increased phosphorylation of eIF2α and protein levels of GRP78/BiP, XBP-1S, and IRE1α in human lung cancer cells. Moreover, compound-K led to the accumulation of intracellular calcium and an increase in m-calpain activities that were both significantly inhibited by pretreatment either with BAPTA-AM (an intracellular Ca2+ chelator or dantrolene (an RyR channel antagonist. These results were correlated with the outcome that compound K induced ER stress-related apoptosis through caspase-12, as z-ATAD-fmk (a specific inhibitor of caspase-12 partially ameliorated this effect. Interestingly, 4-PBA (ER stress inhibitor dramatically improved the compound K-induced apoptosis. Conclusion: Cell survival and intracellular Ca2+ homeostasis during ER stress in human lung cancer cells are important factors in the induction of the compound K-induced apoptotic pathway. Keywords: apoptosis, calcium, compound K, ER stress, lung cancer cells

From Valeriana officinalis to cancer therapy: the success of a bio-sourced compound

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Hamaidia, M.

2016-01-01

Full Text Available Introduction. Over the centuries, bio-sourced compounds isolated from plants, insects and microorganisms have been a potent source of drugs for the treatment of human diseases. Literature. Bio-sourced extracts offer a wide diversity of compounds with a large number of potentially beneficial effects in humans. Serendipity has frequently played a key role in the discovery of new medicines. The canonical discovery of penicillin required both chance and a prepared mind to understand and exploit its potential for the treatment of human infections. Nowadays, most anti-cancer drugs currently in clinical use were at least partly discovered by a "fortunate happenstance". Conclusions. In this review, we recapitulate the story of one of these compounds, 2-propylpentanoic acid, derived from the Valeriana officinalis flowering plant and its path to validation as a cancer treatment.

Urinary levels of N-nitroso compounds in relation to risk of gastric cancer: findings from the shanghai cohort study.

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Xu, Ling; Qu, Yong-Hua; Chu, Xin-Di; Wang, Renwei; Nelson, Heather H; Gao, Yu-Tang; Yuan, Jian-Min

2015-01-01

N-Nitroso compounds are thought to play a significant role in the development of gastric cancer. Epidemiological data, however, are sparse in examining the associations between biomarkers of exposure to N-nitroso compounds and the risk of gastric cancer. A nested case-control study within a prospective cohort of 18,244 middle-aged and older men in Shanghai, China, was conducted to examine the association between urinary level of N-nitroso compounds and risk of gastric cancer. Information on demographics, usual dietary intake, and use of alcohol and tobacco was collected through in-person interviews at enrollment. Urinary levels of nitrate, nitrite, N-nitroso-2-methylthiazolidine-4-carboxylic acid (NMTCA), N-nitrosoproline (NPRO), N-nitrososarcosine (NSAR), N-nitrosothiazolidine-4-carboxylic acid (NTCA), as well as serum H. pylori antibodies were quantified in 191 gastric cancer cases and 569 individually matched controls. Logistic regression method was used to assess the association between urinary levels of N-nitroso compounds and risk of gastric cancer. Compared with controls, gastric cancer patients had overall comparable levels of urinary nitrate, nitrite, and N-nitroso compounds. Among individuals seronegative for antibodies to H. pylori, elevated levels of urinary nitrate were associated with increased risk of gastric cancer. The multivariate-adjusted odds ratios for the second and third tertiles of nitrate were 3.27 (95% confidence interval = 0.76-14.04) and 4.82 (95% confidence interval = 1.05-22.17), respectively, compared with the lowest tertile (P for trend = 0.042). There was no statistically significant association between urinary levels of nitrite or N-nitroso compounds and risk of gastric cancer. Urinary NMTCA level was significantly associated with consumption of alcohol and preserved meat and fish food items. The present study demonstrates that exposure to nitrate, a precursor of N-nitroso compounds, may increase the risk of gastric cancer among

Inducers of Senescence, Toxic Compounds, and Senolytics: The Multiple Faces of Nrf2-Activating Phytochemicals in Cancer Adjuvant Therapy

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Marco Malavolta

2018-01-01

Full Text Available The reactivation of senescence in cancer and the subsequent clearance of senescent cells are suggested as therapeutic intervention in the eradication of cancer. Several natural compounds that activate Nrf2 (nuclear factor erythroid-derived 2-related factor 2 pathway, which is involved in complex cytoprotective responses, have been paradoxically shown to induce cell death or senescence in cancer. Promoting the cytoprotective Nrf2 pathway may be desirable for chemoprevention, but it might be detrimental in later stages and advanced cancers. However, senolytic activity shown by some Nrf2-activating compounds could be used to target senescent cancer cells (particularly in aged immune-depressed organisms that escape immunosurveillance. We herein describe in vitro and in vivo effects of fifteen Nrf2-interacting natural compounds (tocotrienols, curcumin, epigallocatechin gallate, quercetin, genistein, resveratrol, silybin, phenethyl isothiocyanate, sulforaphane, triptolide, allicin, berberine, piperlongumine, fisetin, and phloretin on cellular senescence and discuss their use in adjuvant cancer therapy. In light of available literature, it can be concluded that the meaning and the potential of adjuvant therapy with natural compounds in humans remain unclear, also taking into account the existence of few clinical trials mostly characterized by uncertain results. Further studies are needed to investigate the therapeutic potential of those compounds that display senolytic activity.

Methods to Develop Inhalation Cancer Risk Estimates for Chromium and Nickel Compounds

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This document summarizes the approaches and rationale for the technical and scientific considerations used to derive inhalation cancer risks for emissions of chromium and nickel compounds from electric utility steam generating units.

Understanding the Effectiveness of Natural Compound Mixtures in Cancer through Their Molecular Mode of Action

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Thazin Nwe Aung

2017-03-01

Full Text Available Many approaches to cancer management are often ineffective due to adverse reactions, drug resistance, or inadequate target specificity of single anti-cancer agents. In contrast, a combinatorial approach with the application of two or more anti-cancer agents at their respective effective dosages can achieve a synergistic effect that boosts cytotoxicity to cancer cells. In cancer, aberrant apoptotic pathways allow cells that should be killed to survive with genetic abnormalities, leading to cancer progression. Mutations in apoptotic mechanism arising during the treatment of cancer through cancer progression can consequently lead to chemoresistance. Natural compound mixtures that are believed to have multiple specific targets with minimal acceptable side-effects are now of interest to many researchers due to their cytotoxic and chemosensitizing activities. Synergistic interactions within a drug mixture enhance the search for potential molecular targets in cancer cells. Nonetheless, biased/flawed scientific evidence from natural products can suggest false positive therapeutic benefits during drug screening. In this review, we have taken these factors into consideration when discussing the evidence for these compounds and their synergistic therapeutic benefits in cancer. While there is limited evidence for clinical efficacy for these mixtures, in vitro data suggest that these preparations merit further investigation, both in vitro and in vivo.

Texas Native Plants Yield Compounds with Cytotoxic Activities against Prostate Cancer Cells.

Science.gov (United States)

Shaffer, Corena V; Cai, Shengxin; Peng, Jiangnan; Robles, Andrew J; Hartley, Rachel M; Powell, Douglas R; Du, Lin; Cichewicz, Robert H; Mooberry, Susan L

2016-03-25

There remains a critical need for more effective therapies for the treatment of late-stage and metastatic prostate cancers. Three Texas native plants yielded three new and three known compounds with antiproliferative and cytotoxic activities against prostate cancer cells with IC50 values in the range of 1.7-35.0 μM. A new sesquiterpene named espadalide (1), isolated from Gochnatia hypoleuca, had low micromolar potency and was highly effective in clonogenic assays. Two known bioactive germacranolides (2 and 3) were additionally isolated from G. hypoleuca. Dalea frutescens yielded two new isoprenylated chalcones, named sanjuanolide (4) and sanjoseolide (5), and the known sesquiterpenediol verbesindiol (6) was isolated from Verbesina virginica. Mechanistic studies showed that 1-4 caused G2/M accumulation and the formation of abnormal mitotic spindles. Tubulin polymerization assays revealed that 4 increased the initial rate of tubulin polymerization, but did not change total tubulin polymer levels, and 1-3 had no effects on tubulin polymerization. Despite its cytotoxic activity, compound 6 did not initiate changes in cell cycle distribution and has a mechanism of action different from the other compounds. This study demonstrates that new compounds with significant biological activities germane to unmet oncological needs can be isolated from Texas native plants.

Bradykinin-related compounds as new drugs for cancer and inflammation.

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Stewart, John M; Gera, Lajos; Chan, Daniel C; Bunn, Paul A; York, Eunice J; Simkeviciene, Vitalija; Helfrich, Barbara

2002-04-01

Bradykinin (BK) (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) is an important growth factor for small-cell lung cancer (SCLC) and prostate cancer (PC). These cancers have cells of neuroendocrine origin and express receptors for a variety of neuropeptides. BK receptors are expressed on almost all lung cancer cell lines and on many PC cells. Our very potent BK antagonist B9430 (D-Arg-Arg-Pro-Hyp-Gly-lgl-Ser-D-Igl-Oic-Arg) (Hyp, trans-4-hydroxy-L-proline; Ig1, alpha-2-indanylglycine; Oic, octahydroindole-2-carboxylic acid) is a candidate anti-inflammatory drug but does not inhibit growth of SCLC or PC. When B9430 is dimerized by N-terminal cross-linking with a suberimide linker, the product B9870 is a potent growth inhibitor for SCLC both in vitro and in vivo in athymic nude mice. Daily i.p. injection at 5 mg x kg(-1) day(-1) beginning on day 8 after SCLC SHP-77 cell implantation gave 65% inhibition of tumor growth. B9870 stimulates apoptosis in SCLC by a novel "biased agonist" action. We have also developed new small mimetic antagonists. BKM-570 (F5C-OC2Y-Atmp) (F5C, pentafluorocinnamic acid; OC2Y, O-2,6-dichlorobenzyl tyrosine; Atmp, 4-amino-2,2,6,6-tetramethylpiperidine) is very potent for inhibition of SHP-77 growth in nude mice. When injected daily i.p. at 5 mg x kg(-1), M-570 gave 90% suppression of tumor growth. M-570 is more potent than the well-known anticancer drug cisPlatin (60% inhibition) or the recently developed SU5416 (40% inhibition) in this model. M-570 also showed activity against various other cancer cell lines in vitro (SCLC, non-SCLC, lung, prostate, colon, cervix) and inhibited growth of prostate cell line PC3 in nude mice. M-570 and related compounds evidently act in vivo through pathways other than BK receptors. These compounds have clinical potential for treatment of human lung and prostate cancers.

Efficacy of Compound Kushen Injection in Relieving Cancer-Related Pain: A Systematic Review and Meta-Analysis

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Yu-ming Guo

2015-01-01

Full Text Available Despite widespread popular use of complementary and alternative medicine (CAM therapies, a rigorous evidence based on the efficacy of compound kushen injection (CKI for cancer-related pain is lacking. In this study, we evaluated the efficacy and safety of compound kushen injection and provided information for current or future research and clinical application. Sixteen trials were identified with a total of 1564 patients. The total pain relief rate of CKI plus chemotherapy is better than chemotherapy except for colorectal cancer. The treatment groups achieved a reduction in the incidences of leukopenia and gastrointestinal, hepatic, and renal functional lesion. However, there is paucity of multi-institutional RCTs evaluating compound kushen injection for cancer pain with adequate power, duration, and sham control. The quantity and quality of RCTs are lower so that we still have to boost the research level through scientific design and normative report.

A Phenotypic Cell-Binding Screen Identifies a Novel Compound Targeting Triple-Negative Breast Cancer.

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Chen, Luxi; Long, Chao; Youn, Jonghae; Lee, Jiyong

2018-06-11

We describe a "phenotypic cell-binding screen" by which therapeutic candidate targeting cancer cells of a particular phenotype can be isolated without knowledge of drug targets. Chemical library beads are incubated with cancer cells of the phenotype of interest in the presence of cancer cells lacking the phenotype of interest, and then the beads bound to only cancer cells of the phenotype of interest are selected as hits. We have applied this screening strategy in discovering a novel compound (LC129-8) targeting triple-negative breast cancer (TNBC). LC129-8 displayed highly specific binding to TNBC in cancer cell lines and patient-derived tumor tissues. LC129-8 exerted anti-TNBC activity by inducing apoptosis, inhibiting proliferation, reversing epithelial-mesenchymal transition, downregulating cancer stem cell activity and blocking in vivo tumor growth.

Therapeutic potential of bryophytes and derived compounds against cancer

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Abhijit Dey

2015-08-01

Full Text Available Bryophytes, taxonomically placed between the algae and the pteridophytes, are divided into three classes such as Liverworts, Hornworts and Mosses. Indigenous use involves this small group of plants to treat various diseases. Bryophytes have been investigated pharmacologically for active biomolecules. Several constituents with therapeutic potential have been isolated, characterized and investigated for antibacterial, antifungal, antiviral, antioxidative, antiinflamatory and anticancerous efficacy. The present review deals with the literature covering the anticancerous potential of bryophytes. Apart from the examples of the compounds and the containing bryophyte genera, the authors have tried to include the examples of cancer cell lines on which the efficacy have been tested and the mode of action of certain cytotoxic agents. Crude extracts and isolated compounds from bryophytes were found to possess potent cytotoxic properties. Different types of terpenoids and bibenzyls have been reported among the most potent cytotoxic compounds. Most of these compounds were found to induce apoptosis by activating a number of genes and enzymes. Biochemical markers such as DNA fragmentation, nuclear condensation, proteolysis of poly (ADP-ribose polymerase, activation of caspases, inhibition of antiapoptotic nuclear transcriptional factor-kappaB, activation of p38 mitogen-activated protein kinase etc. have been found to be associated with apoptotic and necrotic response. This review summarizes recent scientific findings and suggests further investigations to evaluate the cytotoxic efficacy of bryophytes.

Urinary volatile compounds as biomarkers for lung cancer: a proof of principle study using odor signatures in mouse models of lung cancer.

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Koichi Matsumura

2010-01-01

Full Text Available A potential strategy for diagnosing lung cancer, the leading cause of cancer-related death, is to identify metabolic signatures (biomarkers of the disease. Although data supports the hypothesis that volatile compounds can be detected in the breath of lung cancer patients by the sense of smell or through bioanalytical techniques, analysis of breath samples is cumbersome and technically challenging, thus limiting its applicability. The hypothesis explored here is that variations in small molecular weight volatile organic compounds ("odorants" in urine could be used as biomarkers for lung cancer. To demonstrate the presence and chemical structures of volatile biomarkers, we studied mouse olfactory-guided behavior and metabolomics of volatile constituents of urine. Sensor mice could be trained to discriminate between odors of mice with and without experimental tumors demonstrating that volatile odorants are sufficient to identify tumor-bearing mice. Consistent with this result, chemical analyses of urinary volatiles demonstrated that the amounts of several compounds were dramatically different between tumor and control mice. Using principal component analysis and supervised machine-learning, we accurately discriminated between tumor and control groups, a result that was cross validated with novel test groups. Although there were shared differences between experimental and control animals in the two tumor models, we also found chemical differences between these models, demonstrating tumor-based specificity. The success of these studies provides a novel proof-of-principle demonstration of lung tumor diagnosis through urinary volatile odorants. This work should provide an impetus for similar searches for volatile diagnostic biomarkers in the urine of human lung cancer patients.

Release of volatile organic compounds (VOCs from the lung cancer cell line CALU-1 in vitro

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Schubert Jochen

2008-11-01

Full Text Available Abstract Background The aim of this work was to confirm the existence of volatile organic compounds (VOCs specifically released or consumed by lung cancer cells. Methods 50 million cells of the human non-small cell lung cancer (NSCLC cell line CALU-1 were incubated in a sealed fermenter for 4 h or over night (18 hours. Then air samples from the headspace of the culture vessel were collected and preconcentrated by adsorption on solid sorbents with subsequent thermodesorption and analysis by means of gas chromatography mass spectrometry (GC-MS. Identification of altogether 60 compounds in GCMS measurement was done not only by spectral library match, but also by determination of retention times established with calibration mixtures of the respective pure compounds. Results The results showed a significant increase in the concentrations of 2,3,3-trimethylpentane, 2,3,5-trimethylhexane, 2,4-dimethylheptane and 4-methyloctane in the headspace of CALU-1 cell culture as compared to medium controls after 18 h. Decreased concentrations after 18 h of incubation were found for acetaldehyde, 3-methylbutanal, butyl acetate, acetonitrile, acrolein, methacrolein, 2-methylpropanal, 2-butanone, 2-methoxy-2-methylpropane, 2-ethoxy-2-methylpropane, and hexanal. Conclusion Our findings demonstrate that certain volatile compounds can be cancer-cell derived and thus indicative of the presence of a tumor, whereas other compounds are not released but seem to be consumed by CALU-1 cells.

Endogenous versus exogenous exposure to N-nitroso compounds and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST) study.

NARCIS (Netherlands)

Jakszyn, Paula; Bingham, Sheila A; Pera, Guillem; Agudo, Antonio; Luben, Robert; Welch, Ailsa; Boeing, Heiner; Giudice, Giuseppe del; Palli, Domenico; Saieva, Calogero; Krogh, Vittorio; Sacerdote, Carlotta; Tumino, Rosario; Panico, Salvatore; Berglund, Göran; Simán, Henrik; Hallmans, Göran; Sanchez, María José; Larrañaga, Nerea; Barricarte, Aurelio; Chirlaque, María-Dolores; Quirós, José Ramón; Key, Timothy J; Allen, Naomi E; Lund, Eiliv; Carneiro, Fátima; Linseisen, Jakob; Nagel, Gabriele; Overvad, Kim; Tjønneland, Anne; Olsen, Anja; Bueno-de-Mesquita, H Bas; Ocké, Marga C; Peeters, Petra H M; Numans, Mattijs E; Clavel-Chapelon, Françoise; Trichopoulou, Antonia; Fenger, Claus; Stenling, Roger; Ferrari, Pietro; Jenab, Mazda; Norat, Teresa; Riboli, Elio; González, Carlos Alberto

2006-01-01

The risk of gastric cancer (GC) associated with dietary intake of nitrosodimethylamine (NDMA) and endogenous formation of nitroso compounds (NOCs) was investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC). The study included 521,457 individuals and 314 incident

Endogenous versus exogenous exposure to N-Nitroso compounds and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST) study.

NARCIS (Netherlands)

Jakszyn, P.; Bingham, S.; Pera, G.; Agudo, A.; Luben, R.; Welch, A.; Boeing, H.; Giudice, G. del; Palli, D.; Saieva, C.; Krogh, V.; Sacerdote, C.; Tumino, R.; Panico, S.; Berglund, G.; Simán, H.; Hallmans, G.; Sanchez, M.J.; Larrañaga, N.; Barricarte, A.; Chirlaque, M.D.; Quirós, J.R.; Key, T.J.; Allen, N.; Lund, E.; Carneiro, F.; Linseisen, J.; Nagel, G.; Overvad, K.; Tjønneland, A.; Olsen, A.; Bueno-de-Mesquita, H.B.; Ocké, M.O.; Peeters, P.H.M.; Numans, M.E.; Clavel-Chapelon, F.; Trichopoulou, A.; Fenger, C.; Stenling, R.; Ferrari, P.; Jenab, M.; Norat, T.; Riboli, E.; Gonzalez, C.A.

The risk of gastric cancer (GC) associated with dietary intake of Nitrosodimethylamine (NDMA) and endogenous formation of Nitroso compounds (NOCs) was investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC). The study included 521,457 individuals and 314 incident

Modulation of Telomerase Activity in Cancer Cells by Dietary Compounds: A Review

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Takahiro Eitsuka

2018-02-01

Full Text Available Telomerase is expressed in ~90% of human cancer cell lines and tumor specimens, whereas its enzymatic activity is not detectable in most human somatic cells, suggesting that telomerase represents a highly attractive target for selective cancer treatment. Accordingly, various classes of telomerase inhibitors have been screened and developed in recent years. We and other researchers have successfully found that some dietary compounds can modulate telomerase activity in cancer cells. Telomerase inhibitors derived from food are subdivided into two groups: one group directly blocks the enzymatic activity of telomerase (e.g., catechin and sulfoquinovosyldiacylglycerol, and the other downregulates the expression of human telomerase reverse transcriptase (hTERT, the catalytic subunit of human telomerase, via signal transduction pathways (e.g., retinoic acid and tocotrienol. In contrast, a few dietary components, including genistein and glycated lipid, induce cellular telomerase activity in several types of cancer cells, suggesting that they may be involved in tumor progression. This review summarizes the current knowledge about the effects of dietary factors on telomerase regulation in cancer cells and discusses their molecular mechanisms of action.

Rapid recognition of volatile organic compounds with colorimetric sensor arrays for lung cancer screening.

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Zhong, Xianhua; Li, Dan; Du, Wei; Yan, Mengqiu; Wang, You; Huo, Danqun; Hou, Changjun

2018-06-01

Volatile organic compounds (VOCs) in breath can be used as biomarkers to identify early stages of lung cancer. Herein, we report a disposable colorimetric array that has been constructed from diverse chemo-responsive colorants. Distinguishable difference maps were plotted within 4 min for specifically targeted VOCs. Through the consideration of various chemical interactions with VOCs, the arrays successfully discriminate between 20 different volatile organic compounds in breath that are related to lung cancer. VOCs were identified either with the visualized difference maps or through pattern recognition with an accuracy of at least 90%. No uncertainties or errors were observed in the hierarchical cluster analysis (HCA). Finally, good reproducibility and stability of the array was achieved against changes in humidity. Generally, this work provides fundamental support for construction of simple and rapid VOC sensors. More importantly, this approach provides a hypothesis-free array method for breath testing via VOC profiling. Therefore, this small, rapid, non-invasive, inexpensive, and visualized sensor array is a powerful and promising tool for early screening of lung cancer. Graphical abstract A disposable colorimetric array has been developed with broadly chemo-responsive dyes to incorporate various chemical interactions, through which the arrays successfully discriminate 20 VOCs that are related to lung cancer via difference maps alone or chemometrics within 4 min. The hydrophobic porous matrix provides good stability against changes in humidity.

Potential of radioiodinated anti cancer compounds of natural origin for cancer therapy

International Nuclear Information System (INIS)

Pandey, U.; Bapat, K.; Samuel, G.; Venkatesh, M.; Sarma, H.D.

2007-01-01

Plumbagin and Quercetin are naturally occurring compounds which exhibit anti-cancerous activity. To evaluate the effect of radioiodination on cytotoxicity, both Plumbagin and Quercetin were radioiodinated with 125 I. 125 I-Plumbagin and 125 I-Quercetin could be prepared in moderate yields and good radiochemical purity and were characterized using reverse phase HPLC. In Swiss mice bearing fibrosarcoma, 125 I-Plumbagin showed a tumor uptake of ∼2.5%ID/g at 3 h p.i. and ∼0.5%ID/g at 24 h p.i on i.v. injection. When injected intratumorally, greater tumor uptake and retention was observed (∼20%ID/g at 3 h p.i. and ∼14%ID/g at 24 h p.i. respectively). (author)

Bioactive Compound Content and Cytotoxic Effect on Human Cancer Cells of Fresh and Processed Yellow Tomatoes

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Assunta Raiola

2015-12-01

Full Text Available Tomato, as a fresh or processed product, has a high nutritional value due to its content of bioactive components such as phenolic compounds. Few studies describe the effect of processing on antioxidant content and the cancer cell growth inhibition activity. In this study we determined the phenolic and ascorbic acid content of three yellow tomato varieties, before and after thermal processing. Moreover, we determined the antioxidative power and tested the effects of tomato extracts on three human cancer cell lines. We found that the amount of phenolic acids (chlorogenic acid and caffeic acid decreased in all the samples after processing, whereas the flavonoid content increased after the heat treatment in two samples. A cytotoxic effect of tomato extracts was observed only after processing. This result well correlates with the flavonoid content after processing and clearly indicates that processed yellow tomatoes have a high content of bioactive compounds endowed with cytotoxicity towards cancer cells, thus opening the way to obtain tomato-based functional foods.

Medicinal Plants, Effective Plant Compounds (Compositions) and their Effects on Stomach Cancer.

Science.gov (United States)

Aleebrahim-Dehkordy, Elahe; Nasri, Hamid; Baradaran, Azar; Nasri, Parto; Tamadon, Mohammad Reza; Hedaiaty, Mahrang; Beigrezaei, Sara; Rafieian-Kopaei, Mahmoud

2017-01-01

Medicinal plants have special importance around the world. Further, they have been noticed for nutrition and illness treatment such as preparation of anticancer new drugs. Therefore, a wide range of studies have been done on different plants, and their anticancer effects have been investigated. Nowadays, cancer is the most important factor of death rate in the developed and developing countries. Among them, stomach cancer is one of the most common malignancies around the world. At present, it is recognized as the fourth common cancer and the second factor of death rate due to cancer. So far, there has been wide range of effort for cancer treatment; however, in most cases, the response to the treatment has been very weak and often accompanied improper subsidiary effects. The present problems as a consequence of chemical treatment and radiotherapy and many subsidiary problems created due to their use for patients, and also, the resistance to the current treatment has motivated researchers to apply new medicines with more effect and less toxicity. The secondary metabolisms existent in the plants have an important role in the treatment of several diseases such as cancer. This study was conducted to investigate and collect scientific results for stomach cancer and to clarify the role of medicinal plants and secondary plant compounds on its treatment.

Extracts and compounds with anti-diabetic complications and anti-cancer activity from Castanea mollissina Blume (Chinese chestnut).

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Zhang, Lin; Gao, Hui-yuan; Baba, Masaki; Okada, Yoshihito; Okuyama, Toru; Wu, Li-jun; Zhan, Li-bin

2014-10-28

Castanea mollissima Blume (Chinese chestnut), as a food product is known for its various nutrients and functional values to the human health. The present study was carried out to analyze the anti-diabetic complications and anti-cancer activities of the bioactive compounds present in C. mollissima. The kernels (CK), shells (CS) and involucres (CI) parts of C. Blume were extracted with 90% alcohol. The water suspension of these dried alcohol extracts were extracted using EtOAc and n-BuOH successively. The n-BuOH fraction of CI (CI-B) was isolated by silica gel column, Sephadex LH 20 column and preparative HPLC. The isolated compounds were identified by 1H-NMR, 13C-NMR, HMBC, HMQC and ESI-Q-TOF MS, All the fractions and compounds isolated were evaluated on human recombinant aldose reductase (HR-AR) assay, advanced glycation end products (AGEs) formation assay and human COLO 320 DM colon cancer cells inhibitory assay. CI-B was found to show a significant inhibitory effect in above biological screenings. Six flavonoids and three polyphenolic acids were obtained from CI-B. They were identified as kaempferol (1), kaempferol-3-O-[6''-O-(E)-p-coumaroyl]-β-D-glucopyranoside (2), kaempferol-3-O-[6''-O-(E)-p-coumaroyl]-β-D-galactopyranoside (3), kaempferol-3-O-[2''-O-(E)-p-coumaroyl]-β-D-glucopyranoside (4), kaempferol-3-O-[2", 6"-di-O-(E)-p-coumaroyl]-β-D-glucopyranoside (5) and kaempferol-3-O-[2", 6"-di-O-(E)-p-coumaroyl]-β-D-galactopyranoside (6), casuariin (7), casuarinin (8) and castalagin (9). Compounds 2-9 were found to show higher activity than quercetin (positive control) in the AR assay. Compounds 3-6, 8, and 9 showed stronger inhibitory effects than amino guanidine (positive control) on AGEs production. Compounds 4-6, 7, and 8 showed much higher cytotoxic activity than 5-fluorouracil (positive control) against the human COLO 320 DM colon cancer cells. Our results suggest that flavonoids and polyphenolic acids possesses anti-diabetes complications and anti-cancer

Bioactive compounds produced by gut microbial tannase: implications for colorectal cancer development

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Félix eLópez De Felipe

2014-12-01

Full Text Available The microorganisms in the human gastrointestinal tract have a profound influence on the transformation of food into metabolites which can impact human health. Gallic acid and pyrogallol are bioactive compounds displaying diverse biological properties, including carcinogenic inhibiting activities. However its concentration in fruits and vegetables is generally low. These metabolites can be also generated as final products of tannin metabolism by microbes endowed with tannase, which opens up the possibility of their anti-cancer potential being increased. Patients with colorectal cancer display an imbalanced gut microbiota respect to healthy population. The recent use of next generation sequencing technologies has greatly improved knowledge of the identity of bacterial species that colonize non-tumorous and tumorous tissues of colorectal cancer patients. This information provides a unique opportunity to shed light on the role played by gut microorganisms in the different stages of this disease. We here review the recently published gut microbiome associated to colorectal cancer patients and highlight tannase as an underlying gene function of bacterial species that selectively colonize tumorous tissues, but not adjacent non-malignant

Targeting Anti-Cancer Active Compounds: Affinity-Based Chromatographic Assays

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de Moraes, Marcela Cristina; Cardoso, Carmen Lucia; Seidl, Claudia; Moaddel, Ruin; Cass, Quezia Bezerra

2016-01-01

Affinity-based chromatography assays encompass the use of solid supports containing immobilized biological targets to monitor binding events in the isolation , identification and/or characterization of bioactive compounds. This powerful bioanalytical technique allows the screening of potential binders through fast analyses that can be directly performed using isolated substances or complex matrices. An overview of the recent researches in frontal and zonal affinity-based chromatography screening assays, which has been used as a tool in the identification and characterization of new anti-cancer agents, is discussed. In addition, a critical evaluation of the recently emerged ligands fishing assays in complex mixtures is also discussed. PMID:27306095

War games: using MRP (material requirements planning) audits to pinpoint problems and keep the competitive edge.

Science.gov (United States)

Porter, S H; Yocus, T E

1994-05-01

In today's world, it is a challenge just to stay in business, let alone remain competitive in a specific industry. We will show you how to pinpoint MRP II problems and attack them through self-assessment audits. You will discover the secrets of breaking down barriers between Master Schedulers, Material Planners, Production Control Planners, and the Manufacturing Line. Self-assessment audits are one way to take care of your planning functions before outside auditors take care of them for you.

Novel Platinum (Pt)-Vandetanib Hybrid Compounds: Design, Synthesis and Investigation of Anti-cancer Activity and Mechanism of Action

Science.gov (United States)

Fei, Rong

Purpose: Lung cancer is one of the most common cancers and non-small cell lung cancer (NSCLC) accounts for 80-85% of lung cancers. 70% of individuals with NSCLC harboring somatic mutations in exons of the epidermal growth factor receptor (EGFR) gene that encode tyrosine kinase domain. EGFR tyrosine kinase inhibitors (TKIs) are promising molecular targeted therapy for NSCLC with sensitizing EGFR mutations. However, secondary mutation of EGFR after treatment of TKIs develops resistance. Vandetanib is introduced to overcome erlotinib resistance as a multi-targeted TKI. However, its anticancer effect is still compromised by EGFR T790M mutation. Therefore, new molecular anticancer strategies are necessarily needed. In this study, vandetanib is incorporated with Pt-based anticancer agents as hybrid compounds, aiming to circumvent TKI resistance. Furthermore, hybrid compounds are investigated in cisplatin resistant problem to expect to overcome resistance by introduction of vandetanib. Methods: Three novel Pt-vandetanib hybrid compounds were synthesized and its physicochemical properties were characterized. Anticancer activity and cytotoxicity were evaluated by sulforhodamine B assay and lactate dehydrogenase release. Docking simulation was performed to investigate the interaction of compounds with EGFR harboring different mutations. Inhibition efficacy of hybrids to kinases was evaluated by kinase inhibition profiling service and cell-free kinase inhibition assay. Mechanistic studies on cytotoxicity activity of the hybrid compounds were carried out. DNA damage response of hybrid compounds was further investigated in KB cells. The cytotoxicity of hybrids was tested in cisplatin resistant KB CP20 cells. Mechanistic of anticancer activity was studied to test inhibition on oncoprotein CIP2Aand DNA damage. Results: Platinum-vandetanib hybrid compounds were synthesized and test to be stable under extracellular condition. Hybrids reacted with 5'-GMP2- and glutathione, and both

Pinpointing Phosphorylation Sites: Quantitative Filtering and a Novel Site-specific x-Ion Fragment

DEFF Research Database (Denmark)

Kelstrup, Christian D; Hekmat, Omid; Francavilla, Chiara

2011-01-01

Phosphoproteomics deals with the identification and quantification of thousands of phosphopeptides. Localizing the phosphorylation site is however much more difficult than establishing the identity of a phosphorylated peptide. Further, recent findings have raised doubts of the validity of the site......-phase phosphate rearrangement reactions during collision-induced dissociation (CID) and used these spectra to devise a quantitative filter that by comparing signal intensities of putative phosphorylated fragment ions with their nonphosphorylated counterparts allowed us to accurately pinpoint which fragment ions...... contain a phosphorylated residue and which ones do not. We also evaluated higher-energy collisional dissociation (HCD) and found this to be an accurate method for correct phosphorylation site localization with no gas-phase rearrangements observed above noise level. Analyzing a large set of HCD spectra...

[Screening of anti-lung cancer bioactive compounds from Curcuma longa by target cell extraction and UHPLC/LTQ Orbitrap MS].

Science.gov (United States)

Zhou, Jian-Liang; Wu, Ye-Qing; Tan, Chun-Mei; Zhu, Ming; Ma, Lin-Ke

2016-10-01

A target cell extraction-chemical profiling method based on human alveolar adenocarcinoma cell line (A549 cells) and UHPLC/LTQ Orbitrap MS for screening the anti-lung cancer bioactive compounds from Curcuma longa has been developed in this paper. According to the hypothesis that when cells are incubated together with the extract of Curcuma longa, the potential bioactive compounds in the extract should selectively combine with the cells, then the cell-binding compounds could be separated and analyzed by LC-MS. The bioactive compounds in C. longa are lipophilic components. They intend to be absorbed on the inner wall of cell culture flask when they were incubated with A549 cells, which will produce interference in the blank solution. In this paper, by using cells digestion and multi-step centrifugation and transfer strategy, the interference problem has been solved. Finally, using the developed method, three cell-binding compounds were screened out and were identified as bisdemethoxycurcumin, demethoxycurcumin, and curcumin. These compounds are the main bioactive compounds with anti-lung cancer bioactivity in C. longa. The improved method developed in this paper could avoid the false positive results due to the absorption of lipophilic compounds on the inner wall of cell culture flask, which will to be an effective complementary method for current target cell extraction-chemical profiling technology. Copyright© by the Chinese Pharmaceutical Association.

Avoidable cancers in the Nordic countries. Diet, obesity and low physical activity

DEFF Research Database (Denmark)

Winther, J F; Dreyer, L; Overvad, K

1997-01-01

through well-described modifications of dietary habits. During the last 10 years, low physical activity has been pinpointed as a risk factor for cancers at various sites, especially the colon; however, the causal mechanism is still unknown. Obesity, defined as a body mass index of 30 or more...... from case-control studies, but have not been confirmed in large population-based cohort studies. Although the research in this area indicates that diet is important in cancer prevention, current knowledge does not allow reliable estimates of the numbers and proportions of cancers that could be avoided...

Infrared-faint radio sources in the SERVS deep fields. Pinpointing AGNs at high redshift

Science.gov (United States)

Maini, A.; Prandoni, I.; Norris, R. P.; Spitler, L. R.; Mignano, A.; Lacy, M.; Morganti, R.

2016-12-01

Context. Infrared-faint radio sources (IFRS) represent an unexpected class of objects which are relatively bright at radio wavelength, but unusually faint at infrared (IR) and optical wavelengths. A recent and extensive campaign on the radio-brightest IFRSs (S1.4 GHz≳ 10 mJy) has provided evidence that most of them (if not all) contain an active galactic nuclei (AGN). Still uncertain is the nature of the radio-faintest IFRSs (S1.4 GHz≲ 1 mJy). Aims: The scope of this paper is to assess the nature of the radio-faintest IFRSs, testing their classification and improving the knowledge of their IR properties by making use of the most sensitive IR survey available so far: the Spitzer Extragalactic Representative Volume Survey (SERVS). We also explore how the criteria of IFRSs can be fine-tuned to pinpoint radio-loud AGNs at very high redshift (z > 4). Methods: We analysed a number of IFRS samples identified in SERVS fields, including a new sample (21 sources) extracted from the Lockman Hole. 3.6 and 4.5 μm IR counterparts of the 64 sources located in the SERVS fields were searched for and, when detected, their IR properties were studied. Results: We compared the radio/IR properties of the IR-detected IFRSs with those expected for a number of known classes of objects. We found that IR-detected IFRSs are mostly consistent with a mixture of high-redshift (z ≳ 3) radio-loud AGNs. The faintest ones (S1.4 GHz 100 μJy), however, could be also associated with nearer (z 2) dust-enshrouded star-burst galaxies. We also argue that, while IFRSs with radio-to-IR ratios >500 can very efficiently pinpoint radio-loud AGNs at redshift 2 < z < 4, lower radio-to-IR ratios ( 100-200) are expected for higher redshift radio-loud AGNs.

Natural compounds' activity against cancer stem-like or fast-cycling melanoma cells.

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Malgorzata Sztiller-Sikorska

Full Text Available BACKGROUND: Accumulating evidence supports the concept that melanoma is highly heterogeneous and sustained by a small subpopulation of melanoma stem-like cells. Those cells are considered as responsible for tumor resistance to therapies. Moreover, melanoma cells are characterized by their high phenotypic plasticity. Consequently, both melanoma stem-like cells and their more differentiated progeny must be eradicated to achieve durable cure. By reevaluating compounds in heterogeneous melanoma populations, it might be possible to select compounds with activity not only against fast-cycling cells but also against cancer stem-like cells. Natural compounds were the focus of the present study. METHODS: We analyzed 120 compounds from The Natural Products Set II to identify compounds active against melanoma populations grown in an anchorage-independent manner and enriched with cells exerting self-renewing capacity. Cell viability, cell cycle arrest, apoptosis, gene expression, clonogenic survival and label-retention were analyzed. FINDINGS: Several compounds efficiently eradicated cells with clonogenic capacity and nanaomycin A, streptonigrin and toyocamycin were effective at 0.1 µM. Other anti-clonogenic but not highly cytotoxic compounds such as bryostatin 1, siomycin A, illudin M, michellamine B and pentoxifylline markedly reduced the frequency of ABCB5 (ATP-binding cassette, sub-family B, member 5-positive cells. On the contrary, treatment with maytansine and colchicine selected for cells expressing this transporter. Maytansine, streptonigrin, toyocamycin and colchicine, even if highly cytotoxic, left a small subpopulation of slow-dividing cells unaffected. Compounds selected in the present study differentially altered the expression of melanocyte/melanoma specific microphthalmia-associated transcription factor (MITF and proto-oncogene c-MYC. CONCLUSION: Selected anti-clonogenic compounds might be further investigated as potential adjuvants

Identification of compounds that selectively target highly chemotherapy refractory neuroblastoma cancer stem cells.

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Díaz-Carballo, David; Acikelli, Ali Haydar; Bardenheuer, Walter; Gustmann, Sebastian; Malak, Sascha; Stoll, Raphael; Kedziorski, Thorsten; Nazif, Mhd Ali; Jastrow, Holger; Wennemuth, Gunter; Dammann, Philip; Feigel, Martin; Strumberg, Dirk

2014-09-01

Relapse of cancer months or years after an apparently successful therapy is probably caused by cancer stem cells (CSCs) due to their intrinsic features like dormant periods, radiorefraction, and acquired multidrug resistance (MDR) phenotypes, among other mechanisms of cellular drug evasiveness. Thus, the lack of currently efficacious interventions remains a major problem in the treatment of malignancies, together with the inability of existing drugs to destroy specifically CSCs. Neuroblastomas per se are highly chemotherapy-refractory extracranial tumors in infants with very low survival rates. So far, no effective cytostatics against this kind of tumors are clinically available. Therefore, we have put much effort into the development of agents to efficiently combat this malignancy. For this purpose, we tested several compounds isolated from Cuban propolis on induced CSCs (iCSC) derived from LAN-1 neuroblastoma cells which expressed several characteristics of tumor-initiating cells both in in-vitro and in-vivo models. Some small molecules such as flavonoids and polycyclic polyprenylated acylphloroglucinols (PPAP) were isolated using successive RT-HPLC cycles and identified employing mass spectrometry and NMR spectroscopic techniques. Their cytotoxicity was first screened in sensitive cell systems by MTT proliferation assays and afterwards studied in less sensitive neuroblastoma iCSC models. We found several compounds with considerable anti-iCSC activity, most of them belonging to the PPAP class. The majority of the compounds act in a pleiotropic manner on the molecular biology of tumors although their specific targets remain unclear. Nevertheless, two substances, one of them a flavonoid, induced a strong disruption of tubulin polymerization. In addition, an unknown compound strongly inhibited replicative enzymes like toposimerases I/II and DNA polymerase. Here, we report for the first time cytotoxic activities of small molecules isolated from Caribbean propolis

Hexavalent Chromium Compounds

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Learn about chromium, exposure to which can increase your risk of lung cancer and cancer of the paranasal sinuses and nasal cavity. Hexavalent chromium compounds have been used as corrosion inhibitors in a wide variety of products and processes.

Visual navigation using edge curve matching for pinpoint planetary landing

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Cui, Pingyuan; Gao, Xizhen; Zhu, Shengying; Shao, Wei

2018-05-01

Pinpoint landing is challenging for future Mars and asteroid exploration missions. Vision-based navigation scheme based on feature detection and matching is practical and can achieve the required precision. However, existing algorithms are computationally prohibitive and utilize poor-performance measurements, which pose great challenges for the application of visual navigation. This paper proposes an innovative visual navigation scheme using crater edge curves during descent and landing phase. In the algorithm, the edge curves of the craters tracked from two sequential images are utilized to determine the relative attitude and position of the lander through a normalized method. Then, considering error accumulation of relative navigation, a method is developed. That is to integrate the crater-based relative navigation method with crater-based absolute navigation method that identifies craters using a georeferenced database for continuous estimation of absolute states. In addition, expressions of the relative state estimate bias are derived. Novel necessary and sufficient observability criteria based on error analysis are provided to improve the navigation performance, which hold true for similar navigation systems. Simulation results demonstrate the effectiveness and high accuracy of the proposed navigation method.

The Influence of Compound Shougong Powder on JAK2-STAT3 Signaling Pathway in Mice with Lewis Lung Cancer

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SHEN Di

2014-12-01

Full Text Available Objective: To observe the influence of Compound Shougong Powder on JAK2-STAT3 signaling pathway in mice with Lewis lung cancer. Methods: Fifty C57BL/6J mice were inoculated with Lewis lung cancer cell line according to the conventional method, 40 mice bearing cancer successfully were selected 6 d later and randomly divided into 5groups, namely negative control group, cis-platinum group, high-dose Compound Shougong Powder group, middle-dose Compound Shougong Powder group and low-dose Compound Shougong Powder group, 8 mice in each group. Negative control group was drenched with normal saline (NS. Compound Shougong Powder groups were drenched with Compound Shougong Powder, 4 mg/kg for high-dose group, 2 mg/kg for middle-dose group, 1 mg/kg for low-dose group, once per day for 14 d; cis-platinum group was orally administrated 4 mg/kg/w, intraperitoneal injection of 0.1 mL for each, once per week for 2 weeks. Mice’s responses to the treatment, activity levels, mental states and so on during the treatment were observed, tumor inhibition rate was calculated, pathomorphological changes of tumor tissues were observed under light microscope after HE staining, and the expression levels of JAK2 and STAT3 proteins were detected by Western Blot. Results: After drug administration, smooth, glossy body hair and good spirit were observed in cisplatin group and high-dose Compound Shougong Powder group; glossier body hair and less activity level in middle- and low- dose Compound Shougong Powder group, and great toxic and side effects, reduced activity level and weary spirit in negative control group. The tumor inhibition rate of cisplatin group, high-, middle- and low-dose Compound Shougong Powder group and negative control group was 57.69%, 53.53%, 48.40%, 38.46% and 38.46%, respectively. The expression levels of JAK2 and STAT3 proteins in drug groups showed decreases to different degrees, and the decreases of JAK2 were more significant. Conclusion: Compound

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation

DEFF Research Database (Denmark)

Gusev, Alexander; Shi, Huwenbo; Kichaev, Gleb

2016-01-01

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined...... with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell...... lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic...

p53-independent structure-activity relationships of 3-ring mesogenic compounds' activity as cytotoxic effects against human non-small cell lung cancer lines.

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Fukushi, Saori; Yoshino, Hironori; Yoshizawa, Atsushi; Kashiwakura, Ikuo

2016-07-25

We recently demonstrated the cytotoxicity of liquid crystal precursors (hereafter referred to as "mesogenic compounds") in the human non-small cell lung cancer (NSCLC) cell line A549 which carry wild-type p53. p53 mutations are observed in 50 % of NSCLC and contribute to their resistance to chemotherapy. To develop more effective and cancer-specific agents, in this study, we investigated the structure-activity relationships of mesogenic compounds with cytotoxic effects against multiple NSCLC cells. The pharmacological effects of mesogenic compounds were examined in human NSCLC cells (A549, LU99, EBC-1, and H1299) and normal WI-38 human fibroblast. Analyses of the cell cycle, cell-death induction, and capsases expression were performed. The 3-ring compounds possessing terminal alkyl and hydroxyl groups (compounds C1-C5) showed cytotoxicity in NSCLC cells regardless of the p53 status. The compounds C1 and C3, which possess a pyrimidine at the center of the core, induced G2/M arrest, while the compounds without a pyrimidine (C2, C4, and C5) caused G1 arrest; all compounds produced caspase-mediated cell death. These events occurred in a p53-independent manner. Furthermore, it was suggested that compounds induced cell death through p53-independent DNA damage-signaling pathway. Compounds C2, C4, and C5 did not show strong cytotoxicity in WI-38 cells, whereas C1 and C3 did. However, the cytotoxicity of compound C1 against WI-38 cells was improved by modulating the terminal alkyl chain lengths of the compound. We showed the p53-indepdent structure-activity relationships of mesogenic compounds related to the cytotoxic effects. These structure-activity relationships will be helpful in the development of more effective and cancer-specific agents.

Chemoprevention of prostate cancer: Natural compounds, antiandrogens, and antioxidants - In vivo evidence

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Nur Özten-Kandas

2011-01-01

Full Text Available Prostate cancer is the leading non-skin malignancy detected in US males and the second cause of death due to male cancer, in the US. Interventions with drugs or diet supplements that slow down the growth and progression of prostate cancer are potentially very effective in reducing the burden of prostate cancer, particularly if these treatments also prevent the de novo development of new prostatic malignancies. Challenges to identify efficacious agents and develop them for chemopreventive application in men at risk for prostate cancer have included uncertainty about which preclinical models have the ability to predict efficacy in men and lack of consensus about which early phase clinical trial designs are the most appropriate and cost-effective to test promising agents. Efficacy studies in animal models have identified several agents with potential chemopreventive activity against prostate cancer, but few of these findings have been translated into clinical trials. This article identifies some of the major issues associated with prostate cancer chemoprevention research and summarizes the most significant current results from animal efficacy studies and human clinical prevention trials. This summary focuses on: (1 Naturally occurring agents and compounds derived from such agents, including green tea and its constituents, silibinin and milk thistle, and genistein and soy, (2 chemoprevention drugs including agents interfering with androgen action, and (3 antioxidants such as selenium, vitamin E, and lycopene. The general lack of activity of antioxidants is discussed, followed by considerations about translation of preclinical chemoprevention efficacy data, focusing on dose, form, bioavailability, and timing of administration of the agent, as well as discussion of study design of clinical trials and the predictive ability of preclinical models.

Hybrid Curcumin Compounds: A New Strategy for Cancer Treatment

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Marie-Hélène Teiten

2014-12-01

Full Text Available Cancer is a multifactorial disease that requires treatments able to target multiple intracellular components and signaling pathways. The natural compound, curcumin, was already described as a promising anticancer agent due to its multipotent properties and huge amount of molecular targets in vitro. Its translation to the clinic is, however, limited by its reduced solubility and bioavailability in patients. In order to overcome these pharmacokinetic deficits of curcumin, several strategies, such as the design of synthetic analogs, the combination with specific adjuvants or nano-formulations, have been developed. By taking into account the risk-benefit profile of drug combinations, as well as the knowledge about curcumin’s structure-activity relationship, a new concept for the combination of curcumin with scaffolds from different natural products or components has emerged. The concept of a hybrid curcumin molecule is based on the incorporation or combination of curcumin with specific antibodies, adjuvants or other natural products already used or not in conventional chemotherapy, in one single molecule. The high diversity of such conjugations enhances the selectivity and inherent biological activities and properties, as well as the efficacy of the parental compound, with particular emphasis on improving the efficacy of curcumin for future clinical treatments.

Research Advances. Image Pinpoints All 5 Million Atoms in Viral Coat; Bilirubin, "Animals-Only" Pigment, Found in Plants; New Evidence Shows Humans Make Salicylic Acid

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King, Angela G.

2009-08-01

Recent "firsts" in chemical research: image of a viral capsid pinpointing 5 million atoms; isolation and identification of an "animal" pigment, bilirubin, from a plant source; evidence that humans make salicylic acid.

Recently confirmed apoptosis-inducing lead compounds isolated from marine sponge of potential relevance in cancer treatment

KAUST Repository

Essack, Magbubah; Bajic, Vladimir B.; Archer, John A.C.

2011-01-01

Despite intense efforts to develop non-cytotoxic anticancer treatments, effective agents are still not available. Therefore, novel apoptosis-inducing drug leads that may be developed into effective targeted cancer therapies are of interest to the cancer research community. Targeted cancer therapies affect specific aberrant apoptotic pathways that characterize different cancer types and, for this reason, it is a more desirable type of therapy than chemotherapy or radiotherapy, as it is less harmful to normal cells. In this regard, marine sponge derived metabolites that induce apoptosis continue to be a promising source of new drug leads for cancer treatments. A PubMed query from 01/01/2005 to 31/01/2011 combined with hand-curation of the retrieved articles allowed for the identification of 39 recently confirmed apoptosis-inducing anticancer lead compounds isolated from the marine sponge that are selectively discussed in this review. 2011 by the authors.

Recently confirmed apoptosis-inducing lead compounds isolated from marine sponge of potential relevance in cancer treatment

KAUST Repository

Essack, Magbubah

2011-09-20

Despite intense efforts to develop non-cytotoxic anticancer treatments, effective agents are still not available. Therefore, novel apoptosis-inducing drug leads that may be developed into effective targeted cancer therapies are of interest to the cancer research community. Targeted cancer therapies affect specific aberrant apoptotic pathways that characterize different cancer types and, for this reason, it is a more desirable type of therapy than chemotherapy or radiotherapy, as it is less harmful to normal cells. In this regard, marine sponge derived metabolites that induce apoptosis continue to be a promising source of new drug leads for cancer treatments. A PubMed query from 01/01/2005 to 31/01/2011 combined with hand-curation of the retrieved articles allowed for the identification of 39 recently confirmed apoptosis-inducing anticancer lead compounds isolated from the marine sponge that are selectively discussed in this review. 2011 by the authors.

A study on volatile organic compounds emitted by in-vitro lung cancer cultured cells using gas sensor array and SPME-GCMS.

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Thriumani, Reena; Zakaria, Ammar; Hashim, Yumi Zuhanis Has-Yun; Jeffree, Amanina Iymia; Helmy, Khaled Mohamed; Kamarudin, Latifah Munirah; Omar, Mohammad Iqbal; Shakaff, Ali Yeon Md; Adom, Abdul Hamid; Persaud, Krishna C

2018-04-02

Volatile organic compounds (VOCs) emitted from exhaled breath from human bodies have been proven to be a useful source of information for early lung cancer diagnosis. To date, there are still arguable information on the production and origin of significant VOCs of cancer cells. Thus, this study aims to conduct in-vitro experiments involving related cell lines to verify the capability of VOCs in providing information of the cells. The performances of e-nose technology with different statistical methods to determine the best classifier were conducted and discussed. The gas sensor study has been complemented using solid phase micro-extraction-gas chromatography mass spectrometry. For this purpose, the lung cancer cells (A549 and Calu-3) and control cell lines, breast cancer cell (MCF7) and non-cancerous lung cell (WI38VA13) were cultured in growth medium. This study successfully provided a list of possible volatile organic compounds that can be specific biomarkers for lung cancer, even at the 24th hour of cell growth. Also, the Linear Discriminant Analysis-based One versus All-Support Vector Machine classifier, is able to produce high performance in distinguishing lung cancer from breast cancer cells and normal lung cells. The findings in this work conclude that the specific VOC released from the cancer cells can act as the odour signature and potentially to be used as non-invasive screening of lung cancer using gas array sensor devices.

Repurposing Established Compounds to Target Pancreatic Cancer Stem Cells (CSCs

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Bernhard W. Renz

2017-06-01

Full Text Available The diagnosis of pancreatic ductal adenocarcinoma (PDAC carries a dismal prognosis, in particular, when patients present with unresectable disease. While significant progress has been made in understanding the biology of PDAC, this knowledge has not translated into a clear clinical benefit and current chemotherapeutic strategies only offer a modest improvement in overall survival. Accordingly, novel approaches are desperately needed. One hypothesis that could—at least in part—explain the desolate response of PDAC to chemotherapy is the so-called cancer stem cell (CSC concept, which attributes specific traits, such as chemoresistance, metastatic potential and a distinct metabolism to a small cellular subpopulation of the whole tumor. At the same time, however, some of these attributes could make CSCs more permissive for novel therapeutic strategies with compounds that are already in clinical use. Most recently, several publications have tried to enlighten the field with the idea of repurposing established drugs for antineoplastic use. As such, recycling drugs could present an intriguing and fast-track method with new therapeutic paradigms in anti-cancer and anti-CSC treatments. Here, we aim to summarize important aspects and novel findings of this emerging field.

Synthesis of Apoptotic New Quinazolinone-Based Compound and Identification of its Underlying Mitochondrial Signalling Pathway in Breast Cancer Cells.

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Zahedifard, Maryam; Faraj, Fadhil Lafta; Paydar, Mohammadjavad; Looi, Chung Yeng; Hasandarvish, Pouya; Hajrezaie, Maryam; Kamalidehghan, Behnam; Majid, Nazia Abdul; Khalifa, Shaden A M; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen; El-Seedi, Hesham R

2015-01-01

The anti-carcinogenic effect of the new quinazolinone compound, named MMD, was tested on MCF-7 human breast cancer cell line. The synthesis of quinazolinone-based compounds attracted strong attention over the past few decades as an alternative mean to produce analogues of natural products. Quinazolinone compounds sharing the main principal core structures are currently introduced in the clinical trials and pharmaceutical markets as anti-cancer agents. Thus, it is of high clinical interest to identify a new drug that could be used to control the growth and expansion of cancer cells. Quinazolinone is a metabolite derivative resulting from the conjugation of 2-aminobenzoyhydrazide and 5-methoxy-2- hydroxybenzaldehyde based on condensation reactions. In the present study, we analysed the influence of MMD on breast cancer adenoma cell morphology, cell cycle arrest, DNA fragmentation, cytochrome c release and caspases activity. MCF-7 is a type of cell line representing the breast cancer adenoma cells that can be expanded and differentiated in culture. Using different in vitro strategies and specific antibodies, we demonstrate a novel role for MMD in the inhibition of cell proliferation and initiation of the programmed cell death. MMD was found to increase cytochrome c release from the mitochondria to the cytosol and this effect was enhanced over time with effective IC50 value of 5.85 ± 0.71 μg/mL detected in a 72-hours treatment. Additionally, MMD induced cell cycle arrest at G0/G1 phase and caused DNA fragmentation with obvious activation of caspase-9 and caspases-3/7. Our results demonstrate a novel role of MMD as an anti-proliferative agent and imply the involvement of mitochondrial intrinsic pathway in the observed apoptosis.

The Immunomodulatory Potential of Selected Bioactive Plant-Based Compounds in Breast Cancer: A Review.

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Baraya, Yushau Shuaibu; Wong, Kah Keng; Yaacob, Nik Soriani

2017-01-01

Breast cancer has continued to cause high cancer death rates among women worldwide. The use of plants' natural products in breast cancer treatment has received more attention in recent years due to their potentially wider safety margin and the potential to complement conventional chemotherapeutic drugs. Plantbased products have demonstrated anticancer potential through different biological pathways including modulation of the immune system. Immunomodulatory properties of medicinal plants have been shown to mitigate breast cancer cell growth. Different immune cell types participate in this process especially cytotoxic T cells and natural killer cells, and cytokines including chemokines and tumor necrosis factor-α. Medicinal plants such as Glycyrrhiza glabra, Uncaria tomentosa, Camellia sinensis, Panax ginseng, Prunus armenaica (apricot), Allium sativum, Arctium lappa and Curcuma longa were reported to hold strong potential in breast cancer treatment in various parts of the world. Interestingly, research findings have shown that these plants possess bioactive immunomodulators as their main constituents producing the anticancer effects. These immunomodulatory compounds include ajoene, arctigenin, β-carotene, curcumin, epigallocatechin-3-gallate, ginsan, glabridin and quinic acid. In this review, we discussed the ability of these eight immunomodulators in regulating the immune system potentially applicable in breast cancer treatment via anti-inflammatory (curcumin, arctigenin, glabridin and ajoene) and lymphocytes activation (β-carotene, epigallocatechin-3-gallate, quinic acid and ginsan) properties, as well as future research direction in their use for breast cancer treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Phenolic compounds from Viscum album tinctures enhanced antitumor activity in melanoma murine cancer cells.

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Melo, Michelle Nonato de Oliveira; Oliveira, Adriana Passos; Wiecikowski, Adalgisa Felippe; Carvalho, Renato Sampaio; Castro, Juliana de Lima; de Oliveira, Felipe Alves Gomes; Pereira, Henrique Marcelo Gualberto; da Veiga, Venicio Feo; Capella, Marcia Marques Alves; Rocha, Leandro; Holandino, Carla

2018-03-01

Cancer is one of the biggest problems in public health worldwide. Plants have been shown important role in anticancer research. Viscum album L. (Santalaceae), commonly known as mistletoe, is a semi-parasitic plant that grows on different host trees. In complementary medicine, extracts from European mistletoe ( Viscum album L.) have been used in the treatment of cancer. The study was conducted to identify chemical composition and antitumor potential of Viscum album tinctures. Chemical analysis performed by high resolution chromatography equipped with high resolution mass spectrometer identified caffeic acid, chlorogenic acid, sakuranetin, isosakuranetin, syringenin 4-O-glucoside, syringenin 4-O-apiosyl-glucoside, alangilignoside C and ligalbumoside A compounds. Some of these compounds are probably responsible for the reduction of tumoral cellular growth in a dose-dependent manner. It was observed that melanoma murine cells (B16F10) were more sensitive to V. album tinctures than human leukaemic cells (K562), besides non-tumoral cells (MA-104) had a much lower cytotoxicity to them. Apoptotic-like cells were observed under light microscopy and were confirmed by a typical DNA fragmentation pattern. Additionally, flow cytometry results using Annexin-V/FITC permitted to quantify increased expression of early and late apoptotic markers on tumoral cells, confirming augmented Sub G0 population, which was probably associated with a consistent decrease in G1, and an increase in S or G2/M populations. Results indicate the chemical composition of V. album tinctures influences the mechanisms of in vitro tumoral cell death, suggesting a potential use in cancer pharmacotherapy research.

Non-coding RNA/microRNA-modulatory dietary factors and natural products for improved cancer therapy and prevention: Alkaloids, organosulfur compounds, aliphatic carboxylic acids and water-soluble vitamins

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Bernhard Biersack

2016-10-01

Full Text Available Non-coding small RNA molecules, the microRNAs (miRNAs, contribute decisively to the epigenetic regulation processes in cancer cells. Problematic pathogenic properties of cancer cells and the response of cancers towards anticancer drugs are highly influenced by miRNAs. Both increased drug activity and formation of tumor resistance are regulated by miRNAs. Further to this, the survival and proliferation of cancer cells and the formation of metastases is based on the modulated expression of certain miRNAs. In particular, drug-resistant cancer stem-like cells (CSCs depend on the presence and absence of specific miRNAs. Fortunately, several small molecule natural compounds were discovered that target miRNAs involved in the modulation of tumor aggressiveness and drug resistance. This review gives an overview of the effects of a selection of naturally occurring small molecules (alkaloids, organosulfur compounds, aliphatic carboxylic acids and water-soluble vitamins on miRNAs that are closely tangled with cancer diseases. Keywords: MiRNA, Alkaloids, Organosulfur compounds, Aliphatic carboxylic acids, Water-soluble vitamins, Anticancer drugs

A mechanistic overview of herbal medicine and botanical compounds to target transcriptional factors in Breast cancer.

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Zhao, Yingke; Liu, Yue

2018-04-01

The abnormalities of transcription factors, such as NF-κB, STAT, estrogen receptor, play a critical role in the initiation and progression of breast cancer. Due to the limitation of current treatment, transcription factors could be promising therapeutic targets, which have received close attention. In this review, we introduced herbal medicines, as well as botanical compounds that had been verified with anti-tumor properties via regulating transcription factors. Herbs, compounds, as well as formulae reported with various transcriptional targets, were summarized thoroughly, to provide implication for the future research on basic experiment and clinical application. Copyright © 2017 Elsevier Ltd. All rights reserved.

A novel compound NSC745885 exerts an anti-tumor effect on tongue cancer SAS cells in vitro and in vivo.

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Yuan-Wu Chen

Full Text Available Oral squamous cell carcinoma (OSCC is a prevalent cancer, especially in developing countries. Anthracyclines and their anthraquinone derivatives, such as doxorubicin, exhibit a cell growth inhibitory effect and have been used as anti-cancer drugs for many years. However, the cardiotoxicity of anthracycline antibiotics is a major concern in their clinical application. NSC745885 is a novel compound synthesized from 1,2-diaminoanthraquinone, which subsequently reacts with thionyl chloride and triethylamine. The present study aimed to investigate the anti-oral cancer potential and the safety of NSC745885.We investigated the anti-cancer potential of NSC745885 in oral squamous carcinoma cell lines and in an in vivo oral cancer xenograft mouse model. The expression of apoptotic related genes were evaluated by real-time RT-PCR and western bloting, and the in vivo assessment of apoptotic marker were measured by immunohistochemical staining. The anti-tumor efficiency and safety between doxorubicin and NSC745885 were also compared.Our results demonstrated that NSC745885 exhibits anti-oral cancer activity through the induction of apoptosis in cancer cells and in tumor-bearing mice, and this treatment did not induce marked toxicity in experimental mice. This compound also exhibits a comparable anti-tumor efficiency and a higher safety in experimental mice when compared to doxorubicin.The data of this study provide evidence for NSC745885 as a potential novel therapeutic drug for the treatment of human OSCC.

Mesua beccariana (Clusiaceae, A Source of Potential Anti-cancer Lead Compounds in Drug Discovery

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Soek Sin Teh

2012-09-01

Full Text Available An investigation on biologically active secondary metabolites from the stem bark of Mesua beccariana was carried out. A new cyclodione, mesuadione (1, along with several known constituents which are beccamarin (2, 2,5-dihydroxy-1,3,4-trimethoxy anthraquinone (3, 4-methoxy-1,3,5-trihydroxyanthraquinone (4, betulinic acid (5 and stigmasterol (6 were obtained from this ongoing research. Structures of these compounds were elucidated by extensive spectroscopic methods, including 1D and 2D-NMR, GC-MS, IR and UV techniques. Preliminary tests of the in vitro cytotoxic activities of all the isolated metabolites against a panel of human cancer cell lines Raji (lymphoma, SNU-1 (gastric carcinoma, K562 (erythroleukemia cells, LS-174T (colorectal adenocarcinoma, HeLa (cervical cells, SK-MEL-28 (malignant melanoma cells, NCI-H23 (lung adenocarcinoma, IMR-32 (neuroblastoma and Hep-G2 (hepatocellular liver carcinoma were carried out using an MTT assay. Mesuadione (1, beccamarin (2, betulinic acid (5 and stigmasterol (6 displayed strong inhibition of Raji cell proliferation, while the proliferation rate of SK-MEL-28 and HeLa were strongly inhibited by stigmasterol (6 and beccamarin (2, indicating these secondary metabolites could be anti-cancer lead compounds in drug discovery.

Dietary nitrates, nitrites, and N-nitroso compounds and cancer risk: a review of the epidemiologic evidence.

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Eichholzer, M; Gutzwiller, F

1998-04-01

Experimental animal studies have shown N-nitroso compounds (NOC) to be potent carcinogens. Epidemiologic evidence of the carcinogenic potential of dietary NOC and precursor nitrates and nitrites in humans remains inconclusive with regard to the risk of stomach, brain, esophageal, and nasopharyngeal cancers. Inadequate available data could obscure a small to moderate effect of NOC.

Dietary Nitrates, Nitrites, and N-Nitroso Compounds and Cancer Risk: a Review of the Epidemiologic Evidence

OpenAIRE

Eichholzer, Monika; Gutzwiller, Felix

2017-01-01

Experimental animal studies have shown N-nitroso compounds (NOC) to be potent carcinogens. Epidemiologic evidence of the carcinogenic potential of dietary NOC and precursor nitrates and nitrites in humans remains inconclusive with regard to the risk of stomach, brain, esophageal, and nasopharyngeal cancers. Inadequate available data could obscure a small to moderate effect of NOC

Effect of the Botanical Compound LCS101 on Chemotherapy-Induced Symptoms in Patients with Breast Cancer: A Case Series Report.

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Samuels, Noah; Maimon, Yair; Zisk-Rony, Rachel Y

2013-01-01

The treatment of breast cancer invariably results in severe and often debilitating symptoms that can cause significant distress and severely impair daily function and quality-of-life (QOL). We treated a series of 20 female breast cancer patients with the botanical compound LCS101 as adjuvant to conventional chemotherapy. At the end of the treatment regimen, patients rated their symptoms. 70% reported that they had either no or mildly severe levels of fatigue; 60% none to mildly severe weakness; 85% none to mildly severe pain; 70% none to mildly severe nausea; and 80% none to mildly severe vomiting. Only 20% reported severe impairment of overall function, and only 40% severely impaired QOL. No toxic effects were attributed by patients to the LCS101 treatment, and 85% reported that they believed the botanical compound had helped reduce symptoms. The effects of LCS101 on clinical outcomes in breast cancer should be tested further using randomized controlled trials.

Diagnosis by Volatile Organic Compounds in Exhaled Breath from Lung Cancer Patients Using Support Vector Machine Algorithm

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Yuichi Sakumura

2017-02-01

Full Text Available Monitoring exhaled breath is a very attractive, noninvasive screening technique for early diagnosis of diseases, especially lung cancer. However, the technique provides insufficient accuracy because the exhaled air has many crucial volatile organic compounds (VOCs at very low concentrations (ppb level. We analyzed the breath exhaled by lung cancer patients and healthy subjects (controls using gas chromatography/mass spectrometry (GC/MS, and performed a subsequent statistical analysis to diagnose lung cancer based on the combination of multiple lung cancer-related VOCs. We detected 68 VOCs as marker species using GC/MS analysis. We reduced the number of VOCs and used support vector machine (SVM algorithm to classify the samples. We observed that a combination of five VOCs (CHN, methanol, CH3CN, isoprene, 1-propanol is sufficient for 89.0% screening accuracy, and hence, it can be used for the design and development of a desktop GC-sensor analysis system for lung cancer.

Diagnosis by Volatile Organic Compounds in Exhaled Breath from Lung Cancer Patients Using Support Vector Machine Algorithm.

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Sakumura, Yuichi; Koyama, Yutaro; Tokutake, Hiroaki; Hida, Toyoaki; Sato, Kazuo; Itoh, Toshio; Akamatsu, Takafumi; Shin, Woosuck

2017-02-04

Monitoring exhaled breath is a very attractive, noninvasive screening technique for early diagnosis of diseases, especially lung cancer. However, the technique provides insufficient accuracy because the exhaled air has many crucial volatile organic compounds (VOCs) at very low concentrations (ppb level). We analyzed the breath exhaled by lung cancer patients and healthy subjects (controls) using gas chromatography/mass spectrometry (GC/MS), and performed a subsequent statistical analysis to diagnose lung cancer based on the combination of multiple lung cancer-related VOCs. We detected 68 VOCs as marker species using GC/MS analysis. We reduced the number of VOCs and used support vector machine (SVM) algorithm to classify the samples. We observed that a combination of five VOCs (CHN, methanol, CH₃CN, isoprene, 1-propanol) is sufficient for 89.0% screening accuracy, and hence, it can be used for the design and development of a desktop GC-sensor analysis system for lung cancer.

Evidence for Morphological Recomposition in Compound Words using MEG

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Teon Lamont Brooks

2015-04-01

Full Text Available Psycholinguistic and electrophysiological studies of lexical processing show convergent evidence for morpheme-based lexical access for morphologically complex words that involves early decomposition into their constituent morphemes followed by some combinatorial operation. Considering that both semantically transparent (e.g., sailboat and semantically opaque (e.g., bootleg compounds undergo morphological decomposition during the earlier stages of lexical processing, subsequent combinatorial operations should account for the difference in the contribution of the constituent morphemes to the meaning of these different word types. In this study we use magnetoencephalography (MEG to pinpoint the neural bases of this combinatorial stage in English compound word recognition. MEG data were acquired while participants performed a word naming task in which three word types, transparent compounds (e.g., roadside, opaque compounds (e.g., butterfly, and morphologically simple words (e.g., brothel were contrasted in a partial-repetition priming paradigm where the word of interest was primed by one of its constituent morphemes. Analysis of onset latency revealed shorter latencies to name compound words than simplex words when primed, further supporting a stage of morphological decomposition in lexical access. An analysis of the associated MEG activity uncovered a region of interest implicated in morphological composition, the Left Anterior Temporal Lobe (LATL. Only transparent compounds showed increased activity in this area from 250 to 470 ms. Previous studies using sentences and phrases have highlighted the role of LATL in performing computations for basic combinatorial operations. Results are in tune with decomposition models for morpheme accessibility early in processing and suggest that semantics play a role in combining the meanings of morphemes when their composition is transparent to the overall word meaning.

Characterization of the apoptotic response induced by the cyanine dye D112: a potentially selective anti-cancer compound.

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Ning Yang

Full Text Available Chemotherapeutic drugs that are used in anti-cancer treatments often cause the death of both cancerous and noncancerous cells. This non-selective toxicity is the root cause of untoward side effects that limits the effectiveness of therapy. In order to improve chemotherapeutic options for cancer patients, there is a need to identify novel compounds with higher discrimination for cancer cells. In the past, methine dyes that increase the sensitivity of photographic emulsions have been investigated for anti-cancer properties. In the 1970's, Kodak Laboratories initiated a screen of approximately 7000 dye structural variants for selective toxicity. Among these, D112 was identified as a promising compound with elevated toxicity against a colon cancer cell line in comparison to a non-transformed cell line. Despite these results changing industry priorities led to a halt in further studies on D112. We decided to revive investigations on D112 and have further characterized D112-induced cellular toxicity. We identified that in response to D112 treatment, the T-cell leukemia cell line Jurkat showed caspase activation, mitochondrial depolarization, and phosphatidylserine externalization, all of which are hallmarks of apoptosis. Chemical inhibition of caspase enzymatic activity and blockade of the mitochondrial pathway through Bcl-2 expression inhibited D112-induced apoptosis. At lower concentrations, D112 induced growth arrest. To gain insight into the molecular mechanism of D112 induced mitochondrial dysfunction, we analyzed the intracellular localization of D112, and found that D112 associated with mitochondria. Interestingly, in the cell lines that we tested, D112 showed increased toxicity toward transformed versus non-transformed cells. Results from this work identify D112 as a potentially interesting molecule warranting further investigation.

The angular structure of ONC201, a TRAIL pathway-inducing compound, determines its potent anti-cancer activity.

Science.gov (United States)

Wagner, Jessica; Kline, Christina Leah; Pottorf, Richard S; Nallaganchu, Bhaskara Rao; Olson, Gary L; Dicker, David T; Allen, Joshua E; El-Deiry, Wafik S

2014-12-30

We previously identified TRAIL-inducing compound 10 (TIC10), also known as NSC350625 or ONC201, from a NCI chemical library screen as a small molecule that has potent anti-tumor efficacy and a benign safety profile in preclinical cancer models. The chemical structure that was originally published by Stahle, et. al. in the patent literature was described as an imidazo[1,2-a]pyrido[4,3-d]pyrimidine derivative. The NCI and others generally accepted this as the correct structure, which was consistent with the mass spectrometry analysis outlined in the publication by Allen et. al. that first reported the molecule's anticancer properties. A recent publication demonstrated that the chemical structure of ONC201 material from the NCI is an angular [3,4-e] isomer of the originally disclosed, linear [4,3-d] structure. Here we confirm by NMR and X-ray structural analysis of the dihydrochloride salt form that the ONC201 material produced by Oncoceutics is the angular [3,4-e] structure and not the linear structure originally depicted in the patent literature and by the NCI. Similarly, in accordance with our biological evaluation, the previously disclosed anti-cancer activity is associated with the angular structure and not the linear isomer. Together these studies confirm that ONC201, produced by Oncoceutics or obtained from the NCI, possesses an angular [3,4-e] structure that represents the highly active anti-cancer compound utilized in prior preclinical studies and now entering clinical trials in advanced cancers.

Chemopreventive Effects of Oplopantriol A, a Novel Compound Isolated from Oplopanax horridus, on Colorectal Cancer

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Zhiyu Zhang

2014-07-01

Full Text Available Oplopanax horridus is a North American botanical that has received limited investigations. We previously isolated over a dozen of the constituents from O. horridus, and among them oplopantriol A (OPT A is a novel compound. In this study, we firstly evaluated the in vivo chemoprevention activities of OPT A using the xenograft colon cancer mouse model. Our data showed that this compound significantly suppressed tumor growth with dose-related effects (p < 0.01. Next, we characterized the compound’s growth inhibitory effects in human colorectal cancer cell lines HCT-116 and SW-480. With OPT A treatment, these malignant cells were significantly inhibited in both a concentration- and time-dependent manner (both p < 0.01. The IC50 was approximately 5 µM for HCT-116 and 7 µM for SW-480 cells. OPT A significantly induced apoptosis and arrested the cell cycle at the G2/M phase. From further mechanism explorations, our data showed that OPT A significantly upregulated the expression of a cluster of genes, especially the tumor necrosis factor receptor family and caspase family, suggesting that the tumor necrosis factor-related apoptotic pathway plays a key role in OPT A induced apoptosis.

Trioorganotin compounds, cognate ligands, of nuclear retinoid X receptors - biological effects in human breats cancer cell lines

Czech Academy of Sciences Publication Activity Database

Brtko, J.; Toporová, L.; Macejová, D.; Hunáková, L.; Bobálová, Janette

2017-01-01

Roč. 10, suppl. 1 (2017), s. 19-19 ISSN 1337-6853. [Mezioborová toxikologická konference /22./ TOXCON 2017. 21.06.2017-23.06.2017, Plzeň] Grant - others:AV ČR(CZ) SAV-15-01 Program:Bilaterální spolupráce Institutional support: RVO:68081715 Keywords : receptor * organotin compounds * cancer

Rapid Diminution in the Level and Activity of DNA-Dependent Protein Kinase in Cancer Cells by a Reactive Nitro-Benzoxadiazole Compound

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Viviane A. O. Silva

2016-05-01

Full Text Available The expression and activity of DNA-dependent protein kinase (DNA-PK is related to DNA repair status in the response of cells to exogenous and endogenous factors. Recent studies indicate that Epidermal Growth Factor Receptor (EGFR is involved in modulating DNA-PK. It has been shown that a compound 4-nitro-7-[(1-oxidopyridin-2-ylsulfanyl]-2,1,3-benzoxadiazole (NSC, bearing a nitro-benzoxadiazole (NBD scaffold, enhances tyrosine phosphorylation of EGFR and triggers downstream signaling pathways. Here, we studied the behavior of DNA-PK and other DNA repair proteins in prostate cancer cells exposed to compound NSC. We showed that both the expression and activity of DNA-PKcs (catalytic subunit of DNA-PK rapidly decreased upon exposure of cells to the compound. The decline in DNA-PKcs was associated with enhanced protein ubiquitination, indicating the activation of cellular proteasome. However, pretreatment of cells with thioglycerol abolished the action of compound NSC and restored the level of DNA-PKcs. Moreover, the decreased level of DNA-PKcs was associated with the production of intracellular hydrogen peroxide by stable dimeric forms of Cu/Zn SOD1 induced by NSC. Our findings indicate that reactive oxygen species and electrophilic intermediates, generated and accumulated during the redox transformation of NBD compounds, are primarily responsible for the rapid modulation of DNA-PKcs functions in cancer cells.

Animacroxam, a Novel Dual-Mode Compound Targeting Histone Deacetylases and Cytoskeletal Integrity of Testicular Germ Cell Cancer Cells.

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Steinemann, Gustav; Dittmer, Alexandra; Kuzyniak, Weronika; Hoffmann, Björn; Schrader, Mark; Schobert, Rainer; Biersack, Bernhard; Nitzsche, Bianca; Höpfner, Michael

2017-11-01

Novel approaches for the medical treatment of advanced solid tumors, including testicular germ cell tumors (TGCT), are desperately needed. Especially, TGCT patients not responding to cisplatin-based therapy need therapeutic alternatives, as there is no effective medical treatment available for this particular subgroup. Here, we studied the suitability of the novel dual-mode compound animacroxam for TGCT treatment. Animacroxam consists of an HDAC-inhibitory hydroxamate moiety coupled to a 4,5-diarylimidazole with inherent cytoskeleton disrupting potency. Animacroxam revealed pronounced antiproliferative, cell-cycle arresting, and apoptosis-inducing effects in TGCT cell lines with different cisplatin sensitivities. The IC 50 values of animacroxam ranged from 0.22 to 0.42 μmol/L and were not correlated to the cisplatin sensitivity of the tumor cells. No unspecific cytotoxicity of animacroxam was observed in either cisplatin-sensitive or resistant TGCT cells, even at doses as high as 10 μmol/L. Furthermore, animacroxam induced the formation of actin stress fibers in cancer cells, thereby confirming the cytoskeleton-disrupting and antimigratory properties of its imidazole moiety. When compared with the clinically established HDAC inhibitor vorinostat, the novel dual-mode compound animacroxam exhibited superior antitumoral efficacy in vitro Animacroxam also reduced the tumor size of TGCT tumors in vivo , as evidenced by performing xenograft experiments on tumor bearing chorioallantoic membranes of fertilizes chicken eggs (CAM assay). The in vivo experiments also revealed a very good tolerability of the compound, and hence, animacroxam may be a promising candidate for innovative treatment of TGCT in general and the more so for platinum-insensitive or refractory TGCT. Mol Cancer Ther; 16(11); 2364-74. ©2017 AACR . ©2017 American Association for Cancer Research.

Detection of colorectal cancer (CRC by urinary volatile organic compound analysis.

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Ramesh P Arasaradnam

Full Text Available Colorectal cancer (CRC is a leading cause of cancer related death in Europe and the USA. There is no universally accepted effective non-invasive screening test for CRC. Guaiac based faecal occult blood (gFOB testing has largely been superseded by Faecal Immunochemical testing (FIT, but sensitivity still remains poor. The uptake of population based FOBt testing in the UK is also low at around 50%. The detection of volatile organic compounds (VOCs signature(s for many cancer subtypes is receiving increasing interest using a variety of gas phase analytical instruments. One such example is FAIMS (Field Asymmetric Ion Mobility Spectrometer. FAIMS is able to identify Inflammatory Bowel disease (IBD patients by analysing shifts in VOCs patterns in both urine and faeces. This study extends this concept to determine whether CRC patients can be identified through non-invasive analysis of urine, using FAIMS. 133 patients were recruited; 83 CRC patients and 50 healthy controls. Urine was collected at the time of CRC diagnosis and headspace analysis undertaken using a FAIMS instrument (Owlstone, Lonestar, UK. Data was processed using Fisher Discriminant Analysis (FDA after feature extraction from the raw data. FAIMS analyses demonstrated that the VOC profiles of CRC patients were tightly clustered and could be distinguished from healthy controls. Sensitivity and specificity for CRC detection with FAIMS were 88% and 60% respectively. This study suggests that VOC signatures emanating from urine can be detected in patients with CRC using ion mobility spectroscopy technology (FAIMS with potential as a novel screening tool.

Detection of colorectal cancer (CRC) by urinary volatile organic compound analysis.

Science.gov (United States)

Arasaradnam, Ramesh P; McFarlane, Michael J; Ryan-Fisher, Courtenay; Westenbrink, Erik; Hodges, Phoebe; Hodges, Paula; Thomas, Matthew G; Chambers, Samantha; O'Connell, Nicola; Bailey, Catherine; Harmston, Christopher; Nwokolo, Chuka U; Bardhan, Karna D; Covington, James A

2014-01-01

Colorectal cancer (CRC) is a leading cause of cancer related death in Europe and the USA. There is no universally accepted effective non-invasive screening test for CRC. Guaiac based faecal occult blood (gFOB) testing has largely been superseded by Faecal Immunochemical testing (FIT), but sensitivity still remains poor. The uptake of population based FOBt testing in the UK is also low at around 50%. The detection of volatile organic compounds (VOCs) signature(s) for many cancer subtypes is receiving increasing interest using a variety of gas phase analytical instruments. One such example is FAIMS (Field Asymmetric Ion Mobility Spectrometer). FAIMS is able to identify Inflammatory Bowel disease (IBD) patients by analysing shifts in VOCs patterns in both urine and faeces. This study extends this concept to determine whether CRC patients can be identified through non-invasive analysis of urine, using FAIMS. 133 patients were recruited; 83 CRC patients and 50 healthy controls. Urine was collected at the time of CRC diagnosis and headspace analysis undertaken using a FAIMS instrument (Owlstone, Lonestar, UK). Data was processed using Fisher Discriminant Analysis (FDA) after feature extraction from the raw data. FAIMS analyses demonstrated that the VOC profiles of CRC patients were tightly clustered and could be distinguished from healthy controls. Sensitivity and specificity for CRC detection with FAIMS were 88% and 60% respectively. This study suggests that VOC signatures emanating from urine can be detected in patients with CRC using ion mobility spectroscopy technology (FAIMS) with potential as a novel screening tool.

Effect of Cu(II) coordination compounds on the activity of antioxidant enzymes catalase and superoxide dismutase in patients with colorectal cancer.

Science.gov (United States)

Kubiak, Katarzyna; Malinowska, Katarzyna; Langer, Ewa; Dziki, Łukasz; Dziki, Adam; Majsterek, Ireneusz

2011-03-01

Colorectal cancer (CRC) is a serious medical and economical problem of our times. It is the most common gastrointestinal cancer in the world. In Poland, the treatment and detection of CRC are poorly developed and the pathogenesis is still unclear. One hypothesis suggests a role of reactive oxygen species (ROS) in the pathogenesis of CRC. Experimental studies in recent years confirm the participation of ROS in the initiation and promotion of CRC. The aim of the study was to examine the effect of the following coordination compounds coordination compounds: dinitrate (V) tetra(3,4,5-trimethyl-N1-pyrazole-κN2) copper(II), dichloro di(3,4,5-trimethyl-N1-pyrazole-κN2) copper(II), dinitrate (V) di(1,4,5-trimethyl-N1-pyrazole-κN2) copper(II), dichloro di(1,3,4,5-tetramethyl-N1-pyrazole-κN2) copper(II) on the activity of antioxidant enzymes superoxide dismutase (SOD, ZnCu-SOD) and catalase (CAT) in a group of patients with colorectal cancer (CRC) and in the control group consisting of patients with minor gastrointestinal complaints. The study was conducted in 20 patients diagnosed with colorectal cancer at the age of 66.5±10.2 years (10 men and 10 women) versus the control group of 20 people (10 men and 10 women) aged 57.89±17.10 years without cancer lesions in the biological material - hemolysate prepared in a proportion of 1ml of water per 1 ml of blood. CAT activity was measured by the Beers method (1952), while SOD activity was measured by the Misra and Fridovich method (1972). We found that patients with CRC showed a statistically significant decrease of SOD and CAT activity (CAT - 12,75±1.97 U/g Hb, SOD - 1111.52±155.52 U/g Hb) in comparison with the control group (CAT - 19.65±2,17 U/g Hb, SOD - 2046.26±507.22 U/g Hb). Simultaneously, we observed that the investigated coordination compounds of Cu(II) significantly increased the antioxidant activity of CAT and SOD in patients with CRC (mean: CAT 25.23±4.86 U/g Hb, SOD - 3075.96±940.20 U/g Hb). Patients with

Volatile organic compounds as biomarkers of bladder cancer: Sensitivity and specificity using trained sniffer dogs.

Science.gov (United States)

Willis, Carolyn M; Britton, Lezlie E; Harris, Rob; Wallace, Joshua; Guest, Claire M

In a previous canine study, we demonstrated that volatile organic compounds specific to bladder cancer are present in urine headspace, subsequently showing that up to 70% of tumours can be correctly classified using an electronic nose. This study aimed to evaluate the sensitivity and specificity which can be achieved by a group of four trained dogs. In a series of 30 double-blind test runs, each consisting of one bladder cancer urine sample placed alongside six controls, the highest sensitivity achieved by the best performing dog was 73% (95% CI 55-86%), with the group as a whole correctly identifying the cancer samples 64% (95% CI 55-73%) of the time. Specificity of the dogs individually ranged from 92% (95% CI 82-97%) for urine samples obtained from healthy, young volunteers down to 56% (95% CI 42-68%) for those taken from older patients with non-cancerous urological disease. Odds ratio comparisons confirmed a significant decrease in performance as the extent of urine dipstick abnormality and/or pathology amongst the control population increased. Importantly, however, statistical analysis indicated that covariates such as smoking, gender and age, as well as blood, protein and /or leucocytes in the urine did not significantly alter the odds of response to the cancer samples. Our results provide further evidence that volatile biomarkers for bladder cancer exist in urine headspace, and that these have the potential to be exploited for diagnosis.

Mechanisms and Therapeutic Implications of Cell Death Induction by Indole Compounds

International Nuclear Information System (INIS)

Ahmad, Aamir; Sakr, Wael A.; Rahman, KM Wahidur

2011-01-01

Indole compounds, obtained from cruciferous vegetables, are well-known for their anti-cancer properties. In particular, indole-3-carbinol (I3C) and its dimeric product, 3,3′-diindolylmethane (DIM), have been widely investigated for their effectiveness against a number of human cancers in vitro as well as in vivo. These compounds are effective inducers of apoptosis and the accumulating evidence documenting their ability to modulate multiple cellular signaling pathways is a testimony to their pleiotropic behavior. Here we attempt to update current understanding on the various mechanisms that are responsible for the apoptosis-inducing effects by these compounds. The significance of apoptosis-induction as a desirable attribute of anti-cancer agents such as indole compounds cannot be overstated. However, an equally intriguing property of these compounds is their ability to sensitize cancer cells to standard chemotherapeutic agents. Such chemosensitizing effects of indole compounds can potentially have major clinical implications because these non-toxic compounds can reduce the toxicity and drug-resistance associated with available chemotherapies. Combinational therapy is increasingly being realized to be better than single agent therapy and, through this review article, we aim to provide a rationale behind combination of natural compounds such as indoles with conventional therapeutics

Gigantol Suppresses Cancer Stem Cell-Like Phenotypes in Lung Cancer Cells

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Narumol Bhummaphan

2015-01-01

Full Text Available As cancer stem cells (CSCs contribute to malignancy, metastasis, and relapse of cancers, potential of compound in inhibition of CSCs has garnered most attention in the cancer research as well as drug development fields recently. Herein, we have demonstrated for the first time that gigantol, a pure compound isolated from Dendrobium draconis, dramatically suppressed stem-like phenotypes of human lung cancer cells. Gigantol at nontoxic concentrations significantly reduced anchorage-independent growth and survival of the cancer cells. Importantly, gigantol significantly reduced the ability of the cancer cells to form tumor spheroids, a critical hallmark of CSCs. Concomitantly, the treatment of the compound was shown to reduce well-known lung CSCs markers, including CD133 and ALDH1A1. Moreover, we revealed that gigantol decreased stemness in the cancer cells by suppressing the activation of protein kinase B (Akt signal which in turn decreased the cellular levels of pluripotency and self-renewal factors Oct4 and Nanog. In conclusion, gigantol possesses CSCs suppressing activity which may facilitate the development of this compound for therapeutic approaches by targeting CSCs.

Newly engineered magnetic erythrocytes for sustained and targeted delivery of anti-cancer therapeutic compounds.

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Caterina Cinti

Full Text Available Cytotoxic chemotherapy of cancer is limited by serious, sometimes life-threatening, side effects that arise from toxicities to sensitive normal cells because the therapies are not selective for malignant cells. So how can they be selectively improved? Alternative pharmaceutical formulations of anti-cancer agents have been investigated in order to improve conventional chemotherapy treatment. These formulations are associated with problems like severe toxic side effects on healthy organs, drug resistance and limited access of the drug to the tumor sites suggested the need to focus on site-specific controlled drug delivery systems. In response to these concerns, we have developed a new drug delivery system based on magnetic erythrocytes engineered with a viral spike fusion protein. This new erythrocyte-based drug delivery system has the potential for magnetic-controlled site-specific localization and highly efficient fusion capability with the targeted cells. Here we show that the erythro-magneto-HA virosomes drug delivery system is able to attach and fuse with the target cells and to efficiently release therapeutic compounds inside the cells. The efficacy of the anti-cancer drug employed is increased and the dose required is 10 time less than that needed with conventional therapy.

Newly Engineered Magnetic Erythrocytes for Sustained and Targeted Delivery of Anti-Cancer Therapeutic Compounds

Science.gov (United States)

Taranta, Monia; Naldi, Ilaria

2011-01-01

Cytotoxic chemotherapy of cancer is limited by serious, sometimes life-threatening, side effects that arise from toxicities to sensitive normal cells because the therapies are not selective for malignant cells. So how can they be selectively improved? Alternative pharmaceutical formulations of anti-cancer agents have been investigated in order to improve conventional chemotherapy treatment. These formulations are associated with problems like severe toxic side effects on healthy organs, drug resistance and limited access of the drug to the tumor sites suggested the need to focus on site-specific controlled drug delivery systems. In response to these concerns, we have developed a new drug delivery system based on magnetic erythrocytes engineered with a viral spike fusion protein. This new erythrocyte-based drug delivery system has the potential for magnetic-controlled site-specific localization and highly efficient fusion capability with the targeted cells. Here we show that the erythro-magneto-HA virosomes drug delivery system is able to attach and fuse with the target cells and to efficiently release therapeutic compounds inside the cells. The efficacy of the anti-cancer drug employed is increased and the dose required is 10 time less than that needed with conventional therapy. PMID:21373641

The Candidate Cancer Gene Database: a database of cancer driver genes from forward genetic screens in mice.

Science.gov (United States)

Abbott, Kenneth L; Nyre, Erik T; Abrahante, Juan; Ho, Yen-Yi; Isaksson Vogel, Rachel; Starr, Timothy K

2015-01-01

Identification of cancer driver gene mutations is crucial for advancing cancer therapeutics. Due to the overwhelming number of passenger mutations in the human tumor genome, it is difficult to pinpoint causative driver genes. Using transposon mutagenesis in mice many laboratories have conducted forward genetic screens and identified thousands of candidate driver genes that are highly relevant to human cancer. Unfortunately, this information is difficult to access and utilize because it is scattered across multiple publications using different mouse genome builds and strength metrics. To improve access to these findings and facilitate meta-analyses, we developed the Candidate Cancer Gene Database (CCGD, http://ccgd-starrlab.oit.umn.edu/). The CCGD is a manually curated database containing a unified description of all identified candidate driver genes and the genomic location of transposon common insertion sites (CISs) from all currently published transposon-based screens. To demonstrate relevance to human cancer, we performed a modified gene set enrichment analysis using KEGG pathways and show that human cancer pathways are highly enriched in the database. We also used hierarchical clustering to identify pathways enriched in blood cancers compared to solid cancers. The CCGD is a novel resource available to scientists interested in the identification of genetic drivers of cancer. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Prostate cancer metastasis-driving genes: hurdles and potential approaches in their identification

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Yan Ting Chiang

2014-08-01

Full Text Available Metastatic prostate cancer is currently incurable. Metastasis is thought to result from changes in the expression of specific metastasis-driving genes in nonmetastatic prostate cancer tissue, leading to a cascade of activated downstream genes that set the metastatic process in motion. Such genes could potentially serve as effective therapeutic targets for improved management of the disease. They could be identified by comparative analysis of gene expression profiles of patient-derived metastatic and nonmetastatic prostate cancer tissues to pinpoint genes showing altered expression, followed by determining whether silencing of such genes can lead to inhibition of metastatic properties. Various hurdles encountered in this approach are discussed, including (i the need for clinically relevant, nonmetastatic and metastatic prostate cancer tissues such as xenografts of patients' prostate cancers developed via subrenal capsule grafting technology and (ii limitations in the currently available methodology for identification of master regulatory genes.

Two new acetylenic compounds from Asparagus officinalis.

Science.gov (United States)

Li, Xue-Mei; Cai, Jin-Long; Wang, Wen-Xiang; Ai, Hong-Lian; Mao, Zi-Chao

2016-01-01

Two new acetylenic compounds, asparoffins A (1) and B (2), together with two known compounds, nyasol (3) and 3″-methoxynyasol (4), were isolated from stems of Asparagus officinalis. The structures of two new compounds were elucidated on the basis of detailed spectroscopic analyses (UV, IR, MS, 1D, and 2D NMR). All compounds were evaluated for their cytotoxicities against three human cancer cell lines.

Cancer cell death induced by phosphine gold(I) compounds targeting thioredoxin reductase.

Science.gov (United States)

Gandin, Valentina; Fernandes, Aristi Potamitou; Rigobello, Maria Pia; Dani, Barbara; Sorrentino, Francesca; Tisato, Francesco; Björnstedt, Mikael; Bindoli, Alberto; Sturaro, Alberto; Rella, Rocco; Marzano, Cristina

2010-01-15

The thioredoxin system, composed of thioredoxin reductase (TrxR), thioredoxin (Trx), and NADPH (nicotinamide adenine dinucleotide phosphate), plays a central role in regulating cellular redox homeostasis and signaling pathways. TrxR, overexpressed in many tumor cells and contributing to drug resistance, has emerged as a new target for anticancer drugs. Gold complexes have been validated as potent TrxR inhibitors in vitro in the nanomolar range. In order to obtain potent and selective TrxR inhibitors, we have synthesized a series of linear, 'auranofin-like' gold(I) complexes all containing the [Au(PEt(3))](+) synthon and the ligands: Cl(-), Br(-), cyanate, thiocyanate, ethylxanthate, diethyldithiocarbamate and thiourea. Phosphine gold(I) complexes efficiently inhibited cytosolic and mitochondrial TrxR at concentrations that did not affect the two related oxidoreductases glutathione reductase (GR) and glutathione peroxidase (GPx). The inhibitory effect of the redox proteins was also observed intracellularly in cancer cells pretreated with gold(I) complexes. Gold(I) compounds were found to induce antiproliferative effects towards several human cancer cells some of which endowed with cisplatin or multidrug resistance. In addition, they were able to activate caspase-3 and induce apoptosis observed as nucleosome formation and sub-G1 cell accumulation. The complexes with thiocyanate and xanthate ligands were particularly effective in inhibiting thioredoxin reductase and inducing apoptosis. Pharmacodynamic studies in human ovarian cancer cells allowed for the correlation of intracellular drug accumulation with TrxR inhibition that leads to the induction of apoptosis via the mitochondrial pathway.

Chronic exposure to chlorophenol related compounds in the pesticide production workplace and lung cancer: a meta-analysis.

Science.gov (United States)

Zendehdel, Rezvan; Tayefeh-Rahimian, Raana; Kabir, Ali

2014-01-01

Chlorophenols (CPs) and related phenoxyacetic acids (PAs) are pesticide groups contaminated with highly toxic 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) during production. PAs and CPs exposure is associated with risk of cancer, but the situation regarding lung cancer has not been clearly defined. We proposed a meta-analysis of published researches to evaluate relationship between chronic exposure to PAs and CPs in pesticide production workplaces and the risk of lung cancer. After searching PubMed, Scopus, Scholar Google, Web of Sciences until August 2013, the association between chronic PAs and CPs exposure in production workplace and lung cancer was studied in 15 cohort studies. The standardized mortality rate (SMR) and 95% confidence intervals (CI) were collected from the papers. We used random or fixed-effects models, Egger test, funnel plot and meta regression in our analysis. Five papers with six reports were included in the final analysis. The standardized mortality rate for lung cancer from the random model was 1.18 (95% CI: 1.03-1.35, p=0.014) with moderate heterogeneity. Publication bias was not found for included studies in meta-analysis (p=0.9). Our findings has strengthen the evidence of lung cancer from chronic exposure to chlorophenol related compounds (PAs, CPs).

Medicinal Uses of Inorganic Compounds - 2

Indian Academy of Sciences (India)

In the first part of this article, we described medicinal uses of inorganic compounds relating to cancer care, infection and diabetic control, neurological, cardiovascular and in- flammatory diseases. This article contains further infor- mation on the medicinal uses of inorganic compounds as therapeutic and diagnostic in ...

Avoidable cancers in the Nordic countries. Diet, obesity and low physical activity

DEFF Research Database (Denmark)

Winther, J F; Dreyer, L; Overvad, K

1997-01-01

from case-control studies, but have not been confirmed in large population-based cohort studies. Although the research in this area indicates that diet is important in cancer prevention, current knowledge does not allow reliable estimates of the numbers and proportions of cancers that could be avoided...... through well-described modifications of dietary habits. During the last 10 years, low physical activity has been pinpointed as a risk factor for cancers at various sites, especially the colon; however, the causal mechanism is still unknown. Obesity, defined as a body mass index of 30 or more......In the early 1980s, Doll and Peto estimated that about 35% of all deaths from cancer in the United States were attributable to dietary factors, with a margin of uncertainty ranging from 10 to 70%. Since then, several dietary factors, e.g. fat and meat, have been suggested to increase the risk...

Food systems approach to cancer prevention.

Science.gov (United States)

Vanamala, Jairam

2017-08-13

New cancer cases are expected to surge 57% worldwide in the next two decades. The greatest burden will be in low- and middle-income countries that are ill equipped to face this epidemic. Similarly, in the United States, low-income populations are at greater risk for cancer. As most cancers contain over 50 genetic alterations, and as these alterations define dysregulation of over 10 different critical cellular signaling pathways, a "silver bullet" treatment is not effective against most cancers. Instead, the latest World Cancer Report (2012) suggests a research shift toward developing prevention strategies for cancer. Accumulating evidence suggests that a diet high in plant-based foods is preventive of a variety of chronic diseases, including cancer. A plethora of bioactive compounds-such as polyphenols, glucosinolates and carotenoids in fruits, vegetables, grains, and legumes-are shown to suppress a variety of biological capabilities required for tumor growth. While much research has shown that plant bioactive compounds can suppress sustained proliferative signaling, angiogenesis, and metastasis, as well as promote cancer stem cell apoptosis, public health campaigns to increase fruit and vegetable consumption have, overall, been less effective than desired. Thus, there is a need for innovative strategies to support increased consumption of bioactive compounds for cancer prevention particularly in vulnerable populations. Many practices of the farm-to-fork continuum, including preharvest practices, postharvest storage, and processing and consumer practices, affect a food's bioactive compound content, composition, and chemopreventive bioactivity. Food system practices may be adjusted to reduce the toxic compound levels (e.g., glycoalkaloids in potatoes) and improve the bioactive compound profile, thus, elevate the cancer fighting properties of fruits, vegetables, and other food products. This review presents current scientific evidence outlining farm-to-fork effects

Addiction to Coupling of the Warburg Effect with Glutamine Catabolism in Cancer Cells

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Bradley Smith

2016-10-01

Full Text Available Metabolic reprogramming is critical to oncogenesis, but the emergence and function of this profound reorganization remain poorly understood. Here we find that cooperating oncogenic mutations drive large-scale metabolic reprogramming, which is both intrinsic to cancer cells and obligatory for the transition to malignancy. This involves synergistic regulation of several genes encoding metabolic enzymes, including the lactate dehydrogenases LDHA and LDHB and mitochondrial glutamic pyruvate transaminase 2 (GPT2. Notably, GPT2 engages activated glycolysis to drive the utilization of glutamine as a carbon source for TCA cycle anaplerosis in colon cancer cells. Our data indicate that the Warburg effect supports oncogenesis via GPT2-mediated coupling of pyruvate production to glutamine catabolism. Although critical to the cancer phenotype, GPT2 activity is dispensable in cells that are not fully transformed, thus pinpointing a metabolic vulnerability specifically associated with cancer cell progression to malignancy.

Plant-Derived Anti-Inflammatory Compounds: Hopes and Disappointments regarding the Translation of Preclinical Knowledge into Clinical Progress

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Robert Fürst

2014-01-01

Full Text Available Many diseases have been described to be associated with inflammatory processes. The currently available anti-inflammatory drug therapy is often not successful or causes intolerable side effects. Thus, new anti-inflammatory substances are still urgently needed. Plants were the first source of remedies in the history of mankind. Since their chemical characterization in the 19th century, herbal bioactive compounds have fueled drug development. Also, nowadays, new plant-derived agents continuously enrich our drug arsenal (e.g., vincristine, galantamine, and artemisinin. The number of new, pharmacologically active herbal ingredients, in particular that of anti-inflammatory compounds, rises continuously. The major obstacle in this field is the translation of preclinical knowledge into evidence-based clinical progress. Human trials of good quality are often missing or, when available, are frequently not suitable to really prove a therapeutical value. This minireview will summarize the current situation of 6 very prominent plant-derived anti-inflammatory compounds: curcumin, colchicine, resveratrol, capsaicin, epigallocatechin-3-gallate (EGCG, and quercetin. We will highlight their clinical potential and/or pinpoint an overestimation. Moreover, we will sum up the planned trials in order to provide insights into the inflammatory disorders that are hypothesized to be beneficially influenced by the compound.

The natural compound Guttiferone F sensitizes prostate cancer to starvation induced apoptosis via calcium and JNK elevation.

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Li, Xin; Lao, Yuanzhi; Zhang, Hong; Wang, Xiaoyu; Tan, Hongsheng; Lin, Zhixiu; Xu, Hongxi

2015-04-11

In a cytotoxicity screen in serum-free medium, Guttiferone F showed strong growth inhibitory effect against prostate cancer cells. Prostate cancer cells LNCaP and PC3 were treated with Guttiferone F in serum depleted medium. Sub-G1 phase distributions were estimated with flow cytometry. Mitochondrial disruption was observed under confocal microscope using Mitotracker Red staining. Gene and protein expression changes were detected by real-time PCR and Western blotting. Ca(2+) elevation was examined by Fluo-4 staining under fluorescence microscope. PC3 xenografts in mice were examined by immunohistochemical analysis. Guttiferone F had strong growth inhibitory effect against prostate cancer cell lines under serum starvation. It induced a significant increase in sub-G1 fraction and DNA fragmentation. In serum-free medium, Guttiferone F triggered mitochondria dependent apoptosis by regulating Bcl-2 family proteins. In addition, Guttiferone F attenuated the androgen receptor expression and phosphorylation of ERK1/2, while activating the phosphorylation of JNK and Ca(2+) flux. Combination of caloric restriction with Guttiferone F in vivo could increase the antitumor effect without causing toxicity. Guttiferone F induced prostate cancer cell apoptosis under serum starvation via Ca(2+) elevation and JNK activation. Combined with caloric restriction, Guttiferone F exerted significant growth inhibition of PC3 cells xenograft in vivo. Guttiferone F is therefore a potential anti-cancer compound.

Apoptotic efficiency of aqueous extracts of turmeric, garlic and their active compounds in combination with Tamoxifen in lung and oral cancers: A comparative study

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Satish Kumar Vemuri

2018-06-01

Full Text Available Anticancer treatment against oral and lung cancers has caught the eye of oncologist and researchers worldwide as most common cause deaths in India and worldwide is due to these cancers and most of the treatment strategies employed are not showing any effectiveness against neoplastic ability of the cancers. One of the reasons for cancer deaths could be because of poor prognosis and associated therapies. The existing cancer agents are being re-evaluated and development of new mechanisms of treatment being explored continuously, but it’s inadequate in offering treatment. Therefore, endeavors for new anticancer agents with high efficacy and considerable side effects still going on. The literature reviews shows numerous medicinal plants exhibiting anti-proliferative, pro-apoptotic, anti-metastatic and anti-angiogenic properties and these effects were reported by conducting both in vitro experiments and animal studies. Use of natural phytochemical compounds in cancer chemoprevention is an emerging strategy to forestall the cancer progression or cure cancer.In the present study we have attempted to evaluate the efficacy of Curcumin longa and Allium sativum aqueous extracts individually and in combination with its active compounds (Curcumin and Quercetin and also with Tamoxifen hydrochloride. Our results suggest that aqueous extracts of Curcumin longa and Allium sativum were effective in inducing apoptosis and cell death in two immortal cell lines i.e. A549 and SCC-9 (Adeno carcinoma of lung, squamous cell carcinoma of tongue, but there was no apoptosis or cell senescence in normal cell line (HEK 293. There was significant increase in apoptosis and cell senescence in combination therapy. Hence a combination of natural extracts along with Tamoxifen can be considered an alternate in cancer treatments but this requires more research. Keywords: Curcumin longa, Allium sativum, Tamoxifen hydrochloride, A549, SCC-9, HEK 293 cell lines

Continuous subcutaneous infusion of compound oxycodone for the relief of dyspnea in patients with terminally ill cancer: a retrospective study.

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Kawabata, Masahiro; Kaneishi, Keisuke

2013-05-01

Pain and dyspnea are the most prevalent and distressing symptoms in patients with terminally ill cancer. Evidences have accumulated for the effects of morphine on dyspnea, whereas little is known about the effects of oxycodone on dyspnea. We investigated the effectiveness of oxycodone for dyspnea in patients with terminally ill cancer. The injectable form of compound oxycodone (iOC) containing hydrocotarnine was administered continuously via subcutaneous route. We administered iOC to 136 patients. The effect on dyspnea was less conspicuous than pain, yet iOC was effective for dyspnea with varying degrees. None of the adverse effects observed were serious. These results suggest that continuous subcutaneous administration of oxycodone could be one of the reasonable alternatives in the management of dyspnea in patients with terminally ill cancer.

Discovery of estrogen receptor α modulators from natural compounds in Si-Wu-Tang series decoctions using estrogen-responsive MCF-7 breast cancer cells.

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Liu, Li; Ma, Hongyue; Tang, Yuping; Chen, Wenxing; Lu, Yin; Guo, Jianming; Duan, Jin-Ao

2012-01-01

The binding between the estrogen receptor α (ER-α) and a variety of compounds in traditional Chinese formulae, Si-Wu-Tang (SWT) series decoctions, was studied using a stably-transfected human breast cancer cell line (MVLN). In 38 compounds tested from SWT series decoctions, the estrogen-like activity of 22 compounds was above 60% in 20 μg mL(-1). Furthermore, theoretical affinity of these compounds was certificated using the functional virtual screen of ER-α modulators by FlexX-Pharm. The accuracy of functional virtual screening of ER-α modulators could reach to 77.27%. The results showed that some compounds, such as organic acids and flavones in SWT series decoctions could be used as selective estrogen receptor modulators (SERMs) and could be selected for further development as potential agents for estrogen related diseases. Copyright © 2011 Elsevier Ltd. All rights reserved.

Modulation of the BRCA1 Protein and Induction of Apoptosis in Triple Negative Breast Cancer Cell Lines by the Polyphenolic Compound Curcumin

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Danica L. Rowe

2009-09-01

Full Text Available In the current study, we sought to examine the effects of curcumin in a specific type of breast cancer called triple negative breast cancer. These cancers lack expression of the estrogen and progesterone receptors and do not over-express HER2. Current treatment for triple negative breast cancers is limited to cytotoxic chemotherapy, and upon relapse, there are not any therapies currently available. We demonstrate here that the bioactive food compound curcumin induces DNA damage in triple negative breast cancer cells in association with phosphorylation, increased expression, and cytoplasmic retention of the BRCA1 protein. In addition, curcumin promotes apoptosis and prevents anchorage-independent growth and migration of triple negative breast cancer cells. Apoptosis and BRCA1 modulation were not observed in non-transformed mammary epithelial cells, suggesting curcumin may have limited non-specific toxicity. This study suggests that curcumin and potentially curcumin analogues should be tested further in the context of triple negative breast cancer. These results are novel, having never been previously reported, and suggest that curcumin could provide a novel, non-toxic therapy, which could lead to improved survival for patients with triple negative breast cancer. Curcumin should be studied further in this subset of breast cancer patients, for whom treatment options are severely limited.

Alimentation méditerranéenne et cancers [Mediterranean diet and cancers

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Mariette GERBER

2016-06-01

Full Text Available Cancer prevention through food habits is an important matter of public health, given that everybody is exposed to food. The Mediterranean diet model is briefly reported, together with the way to evaluate the adherence to this diet. However, the original score, made for Mediterranean populations, had to be adapted to Western populations. These modifications pinpoint the peculiar aspects of the Mediterranean diet related to health. The studies reporting on the relationship between Mediterranean diet and cancer mortality, colorectal, breast, prostate and other cancers incidence are described. A risk reduction is generally evoked for these outcomes in Mediterranean countries, but it is more difficult to show in US or North-European country. Enough subjects with sane food habits, capable to reveal an inverse association of a Mediterranean-style diet and cancers, might only be found in large cohorts. In addition, the group of “negative” foods in the score needs to include “junk food”, known to be deleterious, and often part of the habits in these occidental countries. In conclusion, it can be said that a high and diverse consumption of fruits, vegetables, legumes, whole grain cereals is a must, be underlined the importance of olive oil, be mentioned the advantage of eating sea-food at least twice-a-week. Consumption of red and processed meat, dairy foods, and alcohol should be kept low and it is important to avoid sugars, saturated fats, all junk-foods, providing empty calories.

Dietary compounds that induce cancer preventive phase 2 enzymes activate apoptosis at comparable doses in HT29 colon carcinoma cells.

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Kirlin, W G; Cai, J; DeLong, M J; Patten, E J; Jones, D P

1999-10-01

Dietary agents that induce glutathione S-transferases and related detoxification systems (Phase 2 enzyme inducers) are thought to prevent cancer by enhancing elimination of chemical carcinogens. The present study shows that compounds of this group (benzyl isothiocyanate, allyl sulfide, dimethyl fumarate, butylated hydroxyanisole) activated apoptosis in human colon carcinoma (HT29) cells in culture over the same concentration ranges that elicited increases in enzyme activity (5-25, 25-100, 10-100, 15-60 micromol/L, respectively). Pretreatment of cells with sodium butyrate, an agent that induces HT29 cell differentiation, resulted in parallel increases in Phase 2 enzyme activities and induction of apoptosis in response to the inducers. Cell death characteristics included apoptotic morphological changes, appearance of cells at sub-G1 phase on flow cytometry, caspase activation, DNA fragmentation and TUNEL-positive staining. The results suggest that dietary Phase 2 inducers may protect against cancer by a mechanism distinct from and in addition to that associated with enhanced elimination of carcinogens. If this occurs in vivo, diets high in such compounds could eliminate precancerous cells by apoptosis at time points well after initial exposure to chemical mutagens and carcinogens.

Dictyoceratidan poisons: Defined mark on microtubule-tubulin dynamics.

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Gnanambal K, Mary Elizabeth; Lakshmipathy, Shailaja Vommi

2016-03-01

Tubulin/microtubule assembly and disassembly is characterized as one of the chief processes during cell growth and division. Hence drugs those perturb these process are considered to be effective in killing fast multiplying cancer cells. There is a collection of natural compounds which disturb microtubule/tubulin dis/assemblage and there have been a lot of efforts concerted in the marine realm too, to surveying such killer molecules. Close to half the natural compounds shooting out from marine invertebrates are generally with no traceable definite mechanisms of action though may be tough anti-cancerous hits at nanogram levels, hence fatefully those discoveries conclude therein without a capacity of translation from laboratory to pharmacy. Astoundingly at least 50% of natural compounds which have definite mechanisms of action causing disorders in tubulin/microtubule kinetics have an isolation history from sponges belonging to the Phylum: Porifera. Poriferans have always been a wonder worker to treat cancers with a choice of, yet precise targets on cancerous tissues. There is a specific order: Dictyoceratida within this Phylum which has contributed to yielding at least 50% of effective compounds possessing this unique mechanism of action mentioned above. However, not much notice is driven to Dictyoceratidans alongside the order: Demospongiae thus dictating the need to know its select microtubule/tubulin irritants since the unearthing of avarol in the year 1974 till date. Hence this review selectively pinpoints all the compounds, noteworthy derivatives and analogs stemming from order: Dictyoceratida focusing on the past, present and future. Copyright © 2016 Elsevier Inc. All rights reserved.

Cancer sniffer dogs: how can we translate this peculiarity in laboratory medicine? Results of a pilot study on gastrointestinal cancers.

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Panebianco, Concetta; Kelman, Edgar; Vene, Kristel; Gioffreda, Domenica; Tavano, Francesca; Vilu, Raivo; Terracciano, Fulvia; Pata, Illar; Adamberg, Kaarel; Andriulli, Angelo; Pazienza, Valerio

2017-11-27

Identification of cancer biomarkers to allow early diagnosis is an urgent need for many types of tumors, whose prognosis strongly depends on the stage of the disease. Canine olfactory testing for detecting cancer is an emerging field of investigation. As an alternative, here we propose to use GC-Olfactometry (GC/O), which enables the speeding up of targeted biomarker identification and analysis. A pilot study was conducted in order to determine odor-active compounds in urine that discriminate patients with gastrointestinal cancers from control samples (healthy people). Headspace solid phase microextraction (HS-SPME)-GC/MS and GC-olfactometry (GC/O) analysis were performed on urine samples obtained from gastrointestinal cancer patients and healthy controls. In total, 91 key odor-active compounds were found in the urine samples. Although no odor-active biomarkers present were found in cancer carrier's urine, significant differences were discovered in the odor activities of 11 compounds in the urine of healthy and diseased people. Seven of above mentioned compounds were identified: thiophene, 2-methoxythiophene, dimethyl disulphide, 3-methyl-2-pentanone, 4-(or 5-)methyl-3-hexanone, 4-ethyl guaiacol and phenylacetic acid. The other four compounds remained unknown. GC/O has a big potential to identify compounds not detectable using untargeted GC/MS approach. This paves the way for further research aimed at improving and validating the performance of this technique so that the identified cancer-associated compounds may be introduced as biomarkers in clinical practice to support early cancer diagnosis.

Anti-EGFR Therapy: Mechanism and Advances in Clinical Efficacy in Breast Cancer

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John F. Flynn

2009-01-01

Full Text Available This review will focus on recent advances in the application of antiepidermal growth factor receptor (anti-EGFR for the treatment of breast cancer. The choice of EGFR, a member of the ErbB tyrosine kinase receptor family, stems from evidence pinpointing its role in various anti-EGFR therapies. Therefore, an increase in our understanding of EGFR mechanism and signaling might reveal novel targets amenable to intervention in the clinic. This knowledge base might also improve existing medical treatment options and identify research gaps in the design of new therapeutic agents. While the approved use of drugs like the dual kinase inhibitor Lapatinib represents significant advances in the clinical management of breast cancer, confirmatory studies must be considered to foster the use of anti-EGFR therapies including safety, pharmacokinetics, and clinical efficacy.

Natural Compounds Regulate Glycolysis in Hypoxic Tumor Microenvironment

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Jian-Li Gao

2015-01-01

Full Text Available In the early twentieth century, Otto Heinrich Warburg described an elevated rate of glycolysis occurring in cancer cells, even in the presence of atmospheric oxygen (the Warburg effect. Recently it became a therapeutically interesting strategy and is considered as an emerging hallmark of cancer. Hypoxia inducible factor-1 (HIF-1 is one of the key transcription factors that play major roles in tumor glycolysis and could directly trigger Warburg effect. Thus, how to inhibit HIF-1-depended Warburg effect to assist the cancer therapy is becoming a hot issue in cancer research. In fact, HIF-1 upregulates the glucose transporters (GLUT and induces the expression of glycolytic enzymes, such as hexokinase, pyruvate kinase, and lactate dehydrogenase. So small molecules of natural origin used as GLUT, hexokinase, or pyruvate kinase isoform M2 inhibitors could represent a major challenge in the field of cancer treatment. These compounds aim to suppress tumor hypoxia induced glycolysis process to suppress the cell energy metabolism or enhance the susceptibility of tumor cells to radio- and chemotherapy. In this review, we highlight the role of natural compounds in regulating tumor glycolysis, with a main focus on the glycolysis under hypoxic tumor microenvironment.

Respiratory carcinogenicity assessment of soluble nickel compounds.

OpenAIRE

Oller, Adriana R

2002-01-01

The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear...

Vitamin A family compounds, estradiol, and docetaxel in proliferation, apoptosis and immunocytochemical profile of human ovary endometrioid cancer cell line CRL-11731.

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Dorota Lemancewicz

2010-01-01

Full Text Available Endometrioid carcinoma represents approximately 10% of cases of the malignant ovarian epithelial tumors. According to literature, the vitamin A (carotenoids and retinoids plays an essential role in cell proliferation, differentiation and apoptosis in both normal and neoplastic ovarian tissues. Apart from that, the retinoids alter a cytotoxic effect of chemiotherapeutics, i.e. docetaxel, on ovarian cancer cell lines. Retinoids act on cancer cells throughout different mechanism than taxanes, so they may be the potential candidates for the new treatment strategies of ovarian cancer. The aim of the study was to determine the effects of vitamin A family compounds (retinol, beta-carotene, lycopene, all-trans -, 9-cis - and 13-cis retinoic acid on the growth and proliferation of CRL-11731 endometrioid ovary cancer cell line and on docetaxel and estradiol activity in this culture. The assay was based on [3H] thymidine incorporation and the proliferative activity of PCNA- and Ki 67-positive cells. The apoptotic index and expression of the Bcl-2 and p53 antigens in CRL-11731 cells were also studied. Among vitamin A family compounds retinol and carotenoids, but not retinoids, inhibited the growth of cancer cells in dose dependent manner. Only the concentration of 100 muM of docetaxel inhibited incorporation [3H] thymidine into CRL-11731 cancer cells. Retinol (33.4%+/-8.5, carotenoids (beta-carotene 20 muM 4.7%+/-2.9, 50 muM 2.2%+/-0.9; lycopene 10 muM 7.6%+/-0.8, 20 muM 5.2%+/-2.5, 50 muM 2.9%+/-1.2, and 13-cis retinoic acid (19.7%+/-2.2 combined with docetaxel (100 muM significantly decreased the percentage of proliferating cells (p<0.0001. The antiproliferative action of lycopene alone and in combination with docetaxel was also confirmed in immunohistochemical examination (decreased the percentage of PCNA and Ki67 positive cells. Also retinol (10 muM and lycopene (20 and 50 muM combined with estradiol (0.01 muM statistically decreased the percentage of

Targeting Hsp27/eIF4E interaction with phenazine compound: a promising alternative for castration-resistant prostate cancer treatment.

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Hajer, Ziouziou; Claudia, Andrieu; Erik, Laurini; Sara, Karaki; Maurizio, Fermeglia; Ridha, Oueslati; David, Taieb; Michel, Camplo; Olivier, Siri; Sabrina, Pricl; Maria, Katsogiannou; Palma, Rocchi

2017-09-29

The actual strategy to improve current therapies in advanced prostate cancer involves targeting genes activated by androgen withdrawal, either to delay or prevent the emergence of the castration-refractory phenotype. However, these genes are often implicated in several physiological processes, and long-term inhibition of survival proteins might be accompanied with cytotoxic effects. To avoid this problem, an alternative therapeutic strategy relies on the identification and use of compounds that disrupt specific protein-protein interactions involved in androgen withdrawal. Specifically, the interaction of the chaperone protein Hsp27 with the initiation factor eIF4E leads to the protection of protein synthesis initiation process and enhances cell survival during cell stress induced by castration or chemotherapy. Thus, in this work we aimed at i) identifying the interaction site of the Hsp27/eIF4E complex and ii) interfere with the relevant protein/protein association mechanism involved in castration-resistant progression of prostate cancer. By a combination of experimental and modeling techniques, we proved that eIF4E interacts with the C-terminal part of Hsp27, preferentially when Hsp27 is phosphorylated. We also observed that the loss of this interaction increased cell chemo-and hormone-sensitivity. In order to find a potential inhibitor of Hsp27/eIF4E interaction, BRET assays in combination with molecular simulations identified the phenazine derivative 14 as the compound able to efficiently interfere with this protein/protein interaction, thereby inhibiting cell viability and increasing cell death in chemo- and castration-resistant prostate cancer models in vitro and in vivo .

Pharmacologically directed strategies in academic anticancer drug discovery based on the European NCI compounds initiative.

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Hendriks, Hans R; Govaerts, Anne-Sophie; Fichtner, Iduna; Burtles, Sally; Westwell, Andrew D; Peters, Godefridus J

2017-07-11

The European NCI compounds programme, a joint initiative of the EORTC Research Branch, Cancer Research Campaign and the US National Cancer Institute, was initiated in 1993. The objective was to help the NCI in reducing the backlog of in vivo testing of potential anticancer compounds, synthesised in Europe that emerged from the NCI in vitro 60-cell screen. Over a period of more than twenty years the EORTC-Cancer Research Campaign panel reviewed ∼2000 compounds of which 95 were selected for further evaluation. Selected compounds were stepwise developed with clear go/no go decision points using a pharmacologically directed programme. This approach eliminated quickly compounds with unsuitable pharmacological properties. A few compounds went into Phase I clinical evaluation. The lessons learned and many of the principles outlined in the paper can easily be applied to current and future drug discovery and development programmes. Changes in the review panel, restrictions regarding numbers and types of compounds tested in the NCI in vitro screen and the appearance of targeted agents led to the discontinuation of the European NCI programme in 2017 and its transformation into an academic platform of excellence for anticancer drug discovery and development within the EORTC-PAMM group. This group remains open for advice and collaboration with interested parties in the field of cancer pharmacology.

Unpublished facts about cancer at Hiroshima and Nagasaki

International Nuclear Information System (INIS)

Delpla, M.

1985-01-01

The author shows that, in spite of uncertainties concerning dosimetry, scientists conducting research into radiopathology can still find their best data in the case histories of atomic bomb survivors. Using his original method he finds that the relations between dose and cancer risk have the same staged form at Hiroshima and Nagasaki and also after radiotherapy. The three-stage shift along the dose axis is easy to interpret. The recent modification proposed for dosimetry of bomb radiation only modifies the dose at each stage. This dose-risk correlation makes it possible for him to pinpoint the carcinogenic effect of supraliminal doses from this radiation with a retroactivity of over thirty years [fr

Synthesis of Novel Heterocyclic Compounds Incorporate 4,5,6,7-Tetrahydrobenzo[b]thiophene Together with Their Cytotoxic Evaluations.

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Abdallah, Amira Elsayed Mahmoud; Mohareb, Rafat Milad; Khalil, Eid Metwally; Elshamy, Menna Alla Mohamed Abd Elaleem

2017-01-01

The 2-amino-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene was the key starting compound used to synthesize new thiazole, pyrimidine, pyran, pyridine and thiazine derivatives. The cytotoxicity of the synthesized compounds was studied towards the three cancer cell lines namely MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and SF-268 (central nervous system (CNS) cancer) in addition to the normal cell line (WI-38) using doxorubicin as the reference drug. The study showed that compounds 5, 9a, 15b, 17c, 18 and 21b were the most potent compounds.

Phenolic Compounds in Brassica Vegetables

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Pablo Velasco

2010-12-01

Full Text Available Phenolic compounds are a large group of phytochemicals widespread in the plant kingdom. Depending on their structure they can be classified into simple phenols, phenolic acids, hydroxycinnamic acid derivatives and flavonoids. Phenolic compounds have received considerable attention for being potentially protective factors against cancer and heart diseases, in part because of their potent antioxidative properties and their ubiquity in a wide range of commonly consumed foods of plant origin. The Brassicaceae family includes a wide range of horticultural crops, some of them with economic significance and extensively used in the diet throughout the world. The phenolic composition of Brassica vegetables has been recently investigated and, nowadays, the profile of different Brassica species is well established. Here, we review the significance of phenolic compounds as a source of beneficial compounds for human health and the influence of environmental conditions and processing mechanisms on the phenolic composition of Brassica vegetables.

Bioactive Compounds from the Red Sea Marine Sponge Hyrtios Species

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Hani Z. Asfour

2013-03-01

Full Text Available In continuation of our search for drug leads from Red Sea sponges we have investigated the ethyl acetate fraction of the organic extract of the Red Sea sponge Hyrtios species. Bioassay-directed fractionation of the active fraction resulted into the identification of three new alkaloids, hyrtioerectines D–F (1–3. Hyrtioerectines D–F belong to the rare marine alkaloids in which the indole and β-carboline fragments of the molecule are linked through C-3/C-3 of both moieties. The structures of the isolated compounds were established based on different spectroscopic data including UV, IR, 1D and 2D NMR (COSY, HSQC, and HMBC and high-resolution mass spectral studies. The antimicrobial activity against several pathogens and the free radical scavenging activity of the compounds using DPPH reagent were evaluated. In addition, the growth inhibitory activity of the compounds against three cancer cell lines was also evaluated. Hyrtioerectines D–F (1–3 displayed variable antimicrobial, free radical scavenging and cancer growth inhibition activities. Generally, compounds 1 and 3 were more active than compound 2.

Smoking habits of relatives of patients with cancer: cancer diagnosis in the family is an important teachable moment for smoking cessation.

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Hayran, Mutlu; Kilickap, Saadettin; Elkiran, Tamer; Akbulut, Hakan; Abali, Huseyin; Yuce, Deniz; Kilic, Diclehan; Turhal, Serdar

2013-01-01

In this study we aimed to determine the rate and habitual patterns of smoking, intentions of cessation, dependence levels and sociodemographic characteristics of relatives of patients with a diagnosis of cancer. This study was designed by the Turkish Oncology Group, Epidemiology and Prevention Subgroup. The relatives of cancer patients were asked to fill a questionnaire and Fagerstrom test of nicotine dependence. The median ages of those with lower and higher Fagerstrom scores were 40 years and 42 years, respectively. We found no evidence of variation between the two groups for the remaining sociodemographic variables, including the subject's medical status, gender, living in the same house with the patient, their educational status, their family income, closeness to their cancer patients or spending time with them or getting any help or wanting to get some help. Only 2% of the subjects started smoking after cancer was diagnosed in their loved ones and almost 20% of subjects had quit smoking during the previous year. The Fagerstrom score is helpful in determining who would be the most likely to benefit from a cigarette smoking cessation program. Identification of these people with proper screening methods might help us to pinpoint who would benefit most from these programs.

Respiratory carcinogenicity assessment of soluble nickel compounds.

Science.gov (United States)

Oller, Adriana R

2002-10-01

The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear because of limitations of the exposure data, inconsistent results across cohorts, and the presence of mixed exposures to water-insoluble nickel compounds and other confounders that are known or suspected carcinogens. Moreover, well-conducted animal inhalation studies, where exposures were solely to soluble nickel, failed to demonstrate a carcinogenic potential. Similar negative results were seen in animal oral studies. A model exists that relates respiratory carcinogenic potential to the bioavailability of nickel ion at nuclear sites within respiratory target cells. This model helps reconcile human, animal, and mechanistic data for soluble nickel compounds. For inhalation exposures, the predicted lack of bioavailability of nickel ion at target sites suggests that water-soluble nickel compounds, by themselves, will not be complete human carcinogens. However, if inhaled at concentrations high enough to induce chronic lung inflammation, these compounds may enhance carcinogenic risks associated with inhalation exposure to other substances. Overall, the weight of evidence indicates that inhalation exposure to soluble nickel alone will not cause cancer; moreover, if exposures are kept below levels that cause chronic respiratory toxicity, any possible tumor-enhancing effects (particularly in smokers) would be avoided.

Autoimmune progesterone dermatitis: Case report with history of urticaria, petechiae and palpable pinpoint purpura triggered by medical abortion.

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Mbonile, Lumuli

2016-03-17

Autoimmune progesterone dermatitis (APD) is a rare autoimmune response to raised endogenous progesterone levels that occur during the luteal phase of the menstrual cycle. Cutaneous, mucosal lesions and other systemic manifestations develop cyclically during the luteal phase of the menstrual cycle when progesterone levels are elevated. APD symptoms usually start 3 - 10 days before menstruation and resolve 1 - 2 days after menstruation ceases. A 30-year-old woman presented with urticaria, petechiae and palpable pinpoint purpura lesions of the legs, forearms, neck and buttocks 1 week prior to her menses starting and 2 months after a medical abortion. She was diagnosed with allergic contact dermatitis and topical steroids were prescribed. Her skin conditions did not improve and were associated with her menstrual cycle. We performed an intradermal test using progesterone, which was positive. She was treated with oral contraceptive pills and the symptoms were resolved. This is a typical case of APD triggered by increased sensitivity to endogenous progesterone induced a few months after medical abortion.

Small molecule n-(alpha-peroxy) indole compounds and methods of use

KAUST Repository

Wang, Xinbo; Lai, Zhiping; Pan, Yupeng; Huang, Kuo-Wei; Wang, Zhigang

2017-01-01

The invention relates to novel N-(α-peroxy)indole compounds of Formula I and methods for use. (I) The N-(α-peroxy)indole compounds described herein are useful for treating or preventing parasitic infections, bacterial infections, and cancer in subjects. The methods include administering an N-(α-peroxy)indole compound as described herein to a subject. Also described herein are methods for synthesizing N-(α-peroxy )indole compounds.

Small molecule n-(alpha-peroxy) carbazole compounds and methods of use

KAUST Repository

Wang, Xinbo; Lai, Zhiping; Pan, Yupeng; Huang, Kuo-Wei

2017-01-01

The invention relates to novel N-(α-peroxy)carbazole compounds of Formula I and methods for use. (I) The N-(α-peroxy)carbazole compounds described herein are useful for treating or preventing parasitic infections, bacterial infections, and cancer in subjects. The methods include administering an N-(α-peroxy)carbazole compound as described herein to a subject. Also described herein are methods for synthesizing N-(α-peroxy)carbazole compounds.

Small molecule n-(alpha-peroxy) indole compounds and methods of use

KAUST Repository

Wang, Xinbo

2017-11-16

The invention relates to novel N-(α-peroxy)indole compounds of Formula I and methods for use. (I) The N-(α-peroxy)indole compounds described herein are useful for treating or preventing parasitic infections, bacterial infections, and cancer in subjects. The methods include administering an N-(α-peroxy)indole compound as described herein to a subject. Also described herein are methods for synthesizing N-(α-peroxy )indole compounds.

Small molecule n-(alpha-peroxy) carbazole compounds and methods of use

KAUST Repository

Wang, Xinbo

2017-11-16

The invention relates to novel N-(α-peroxy)carbazole compounds of Formula I and methods for use. (I) The N-(α-peroxy)carbazole compounds described herein are useful for treating or preventing parasitic infections, bacterial infections, and cancer in subjects. The methods include administering an N-(α-peroxy)carbazole compound as described herein to a subject. Also described herein are methods for synthesizing N-(α-peroxy)carbazole compounds.

7-(O)-Carboxymethyl daidzein conjugated to N-t-Boc-hexylenediamine: a novel compound capable of inducing cell death in epithelial ovarian cancer stem cells.

Science.gov (United States)

Green, Jamie M; Alvero, Ayesha B; Kohen, Fortune; Mor, Gil

2009-09-01

One of the major difficulties in the treatment of epithelial ovarian cancer (EOC) is the high rate of recurrent disease. This is thought to be due to the survival of a population of chemo-resistant cells within the tumor, the ovarian cancer stem cells (OCSCs), that are able to regenerate the tumor following chemotherapy. Therefore, the identification of a compund that can target the OCSCs is one of the main steps in improving overall survival of ovarian cancer patients. The objective of this study was to determine the effect of N-t-boc-Daidzein, a novel daidzain derivative, on OCSCs. The efficacy of this compound was evaluated in OCSC and mature ovarian cancer cell (mOCC) lines isolated from malignant ovarian cancer asicites. Cells were treated with increasing concentrations of N-t-boc-Daidzein (0.003-10 microM) and cell growth was monitored by "real time in vitro micro-imaging" using the IncuCyte system. Cell viability was measured using the CellTiter 96 Assay. Apoptosis was determined by Caspase-Glo 3/7, 8 and 9 assays. The components of the apoptotic cascade were characterized by western blot analysis. N-t-boc-Daidzein was able to significantly inhibit cell growth and decrease cell viability of OCSC as well as mOCC cells in a dose and time dependent maner. This effect was due to the induction of apoptosis, which is characterized by caspase activation, XIAP and AKT degradation, and mitochondrial depolarization. This study describes a novel compound that can target the OCSCs. These findings may provide vital aide in improving overall survival in patients with EOC.

Influences of Pinpoint Plantar Long-Wavelength Infrared Light Irradiation (Stress-Free Therapy on Chorioretinal Hemodynamics, Atherosclerosis Factors, and Vascular Endothelial Growth Factor

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Keisou Ishimaru

2018-03-01

Full Text Available Background: We previously reported that pinpoint plantar long-wavelength infrared light irradiation (stress-free therapy; SFT is useful for alleviating insulin resistance and improving intracranial blood flow in patients with type 2 diabetes mellitus. This study was undertaken to evaluate the influences of SFT on chorioretinal hemodynamics (retinal artery and vein blood flows as well as atherosclerosis-related factors (TG, LDL-C and VEGF in patients with dyslipidemia. Methods: Four patients with dyslipidemia received 15-minute irradiation with a stress-free apparatus (far-infrared wavelength, 30 mW. Using laser speckle flowgraphy, associations of chorioretinal blood flow with peripheral atherosclerosis-inducing factors/VEGF levels before and after irradiation were analyzed. Results: Chorioretinal blood flow increased, while TG/LDL-C levels decreased, after irradiation. VEGF tended to rise in cases with pre-irradiation baseline levels at the lower limit but tended to decrease in cases in which baseline levels had exceeded the normal range. Conclusion: SFT was suggested to enhance chorioretinal circulation and to normalize VEGF, thereby possibly contributing to amelioration of atherosclerosis-inducing factors. Abnormalities in chorioretinal hemodynamics are known to be highly involved in the pathophysiology of diabetic retinopathy and age-related macular degeneration, and anti-VEGF antibody has been used for treating these conditions. The necessity of risk management, involving chorioretinal blood flow, has been pointed out when dealing with central retinal vein occlusion, diabetes mellitus, ischemic cerebral/cardiac disease, dementia and so on. SFT is therefore a potential complementary medical strategy which can be expected to contribute to normalization of chorioretinal blood flow and atherosclerosis-inducing factors/VEGF levels, and thereby to the prevention of lifestyle-related chronic diseases. Keywords: Pinpoint plantar long

Mechanisms of action of phenolic compounds in olive.

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Rafehi, Haloom; Ververis, Katherine; Karagiannis, Tom C

2012-06-01

Olive oil, an oil rich in monounsaturated fatty acids (MUFCs) and minor constituents including phenolic compounds, is a major component of the Mediterranean diet. The potential health benefits of the Mediterranean diet were highlighted by the seminal Seven Countries Study, and more contemporary research has identified olive oil as a major element responsible for these effects. It is emerging that the phenolic compounds are the most likely candidates accounting for the cardioprotective and cancer preventative effects of extra virgin olive oil (EVOO). In particular, the phenolic compound, hydroxytyrosol has been identified as one of the most potent antioxidants found in olive oil. This review will briefly consider historical aspects of olive oil research and the biological properties of phenolic compounds in olive oil will be discussed. The focus of the discussion will be related to the mechanisms of action of hydroxytyrosol. Studies have demonstrated that hydroxytyrosol induces apoptosis and cell cycle arrest in cancer cells. Further, research has shown that hydroxytyrosol can prevent cardiovascular disease by reducing the expression of adhesion molecules on endothelial cells and preventing the oxidation of low-density lipoprotein (LDL). The molecular mechanisms accounting for these effects are reviewed.

Anti-proliferative, Cytotoxic and NF-ĸB Inhibitory Properties of Spiro(Lactone-Cyclohexanone) Compounds in Human Leukemia.

Science.gov (United States)

Bouhenna, Mustapha M; Orlikova, Barbora; Talhi, Oualid; Schram, Ben; Pinto, Diana C G A; Taibi, Nadia; Bachari, Khaldoun; Diederich, Marc; Silva, Artur M S; Mameri, Nabil

2017-09-01

NF-ĸB affects most aspects of cellular physiology. Deregulation of NF-ĸB signaling is associated with inflammatory diseases and cancer. In this study, we evaluated the cytotoxic and NF-ĸB inhibition potential of new spiro(lactone-cyclohexanone) compounds in two different human leukemia cell lines (U937 and K562). The anti-proliferative effects of the spiro(lactone-cyclohexanone) compounds on human K562 and U937 cell lines was evaluated by trypan blue staining, as well as their involvement in NF-kB regulation were analyzed by luciferase reporter gene assay, Caspase-3/7 activities were evaluated to analyze apoptosis induction. Both spiro(coumarin-cyclohexanone) 4 and spiro(6- methyllactone-cyclohexanone) 9 down-regulated cancer cell viability and proliferation. Compound 4 inhibited TNF-α-induced NF-ĸB activation in a dose-dependent manner and induced caspase-dependent apoptosis in both leukemia cell lines. Results show that compound 4 and compound 9 have potential as anti-cancer agents. In addition, compound 4 exerted NF-kB inhibition activity in leukemia cancer cells. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Dietary N-nitroso compounds, endogenous nitrosation, and the risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study.

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Keszei, András P; Goldbohm, R Alexandra; Schouten, Leo J; Jakszyn, Paula; van den Brandt, Piet A

2013-01-01

Dietary N-nitroso compounds and endogenous nitrosation are important carcinogenic factors, but human evidence of their role is scarce for esophageal cancer and inconsistent for gastric cancer. We studied the relation between risks of esophageal and gastric cancer subtypes and dietary intake of N-nitrosodimethylamine, heme iron, nitrite, and nitrate in the Netherlands Cohort Study. A total of 120,852 men and women aged 55-69 y were recruited in 1986, and diet, based on a 150-item food-frequency questionnaire, and other risk factors were assessed. The cohort was followed for 16.3 y, and 110 esophageal squamous cell carcinoma (ESCC), 151 esophageal adenocarcinoma, 166 gastric cardia adenocarcinoma, and 497 gastric noncardia adenocarcinoma (GNCA) cases were analyzed along with 4032 subcohort members in a case-cohort analysis. Positive associations were observed between N-nitrosodimethylamine intake and ESCC risk (HR for 0.1-μg/d increase in intake: 1.15; 95% CI: 1.05, 1.25; P-trend = 0.01 based on tertiles of intake) and GNCA risk (1.06; 95% CI: 1.01, 1.10; P-trend = 0.09) in men. ESCC risk was associated with nitrite intake (HR for 0.1-mg/d increase: 1.19; 95% CI: 1.05, 1.36; P-trend = 0.06) and heme-iron intake (HR for 1-mg/d increase: 1.83; 95% CI: 0.98, 3.39; P-trend = 0.03). Among women, exposure levels were lower, and we found no convincing positive associations. These results suggest that N-nitroso compounds may influence the risk of ESCC in men, but there are no clear associations for other esophageal and gastric subtypes.

A synergistic antiproliferation effect of curcumin and docosahexaenoic acid in SK-BR-3 breast cancer cells: unique signaling not explained by the effects of either compound alone

International Nuclear Information System (INIS)

Altenburg, Jeffrey D; Bieberich, Andrew A; Terry, Colin; Harvey, Kevin A; VanHorn, Justin F; Xu, Zhidong; Jo Davisson, V; Siddiqui, Rafat A

2011-01-01

Breast cancer is a collection of diseases in which molecular phenotypes can act as both indicators and mediators of therapeutic strategy. Therefore, candidate therapeutics must be assessed in the context of multiple cell lines with known molecular phenotypes. Docosahexaenoic acid (DHA) and curcumin (CCM) are dietary compounds known to antagonize breast cancer cell proliferation. We report that these compounds in combination exert a variable antiproliferative effect across multiple breast cell lines, which is synergistic in SK-BR-3 cells and triggers cell signaling events not predicted by the activity of either compound alone. Dose response curves for CCM and DHA were generated for five breast cell lines. Effects of the DHA+ CCM combination on cell proliferation were evaluated using varying concentrations, at a fixed ratio, of CCM and DHA based on their individual ED 50 . Detection of synergy was performed using nonlinear regression of a sigmoid dose response model and Combination Index approaches. Cell molecular network responses were investigated through whole genome microarray analysis of transcript level changes. Gene expression results were validated by RT-PCR, and western blot analysis was performed for potential signaling mediators. Cellular curcumin uptake, with and without DHA, was analyzed via flow cytometry and HPLC. CCM+DHA had an antiproliferative effect in SK-BR-3, MDA-MB-231, MDA-MB-361, MCF7 and MCF10AT cells. The effect was synergistic for SK-BR-3 (ER - PR - Her2 + ) relative to the two compounds individually. A whole genome microarray approach was used to investigate changes in gene expression for the synergistic effects of CCM+DHA in SK-BR-3 cells lines. CCM+DHA triggered transcript-level responses, in disease-relevant functional categories, that were largely non-overlapping with changes caused by CCM or DHA individually. Genes involved in cell cycle arrest, apoptosis, inhibition of metastasis, and cell adhesion were upregulated, whereas genes

Metastasis: recent discoveries and novel perioperative treatment strategies with particular interest in the hemostatic compound desmopressin.

Science.gov (United States)

Alonso, D F; Ripoll, G V; Garona, J; Iannucci, N B; Gomez, D E

2011-11-01

Metastatic disease is responsible for most of cancer lethality. A main obstacle for therapy of advanced cancers is that the outcome of metastasis depends on a complex interplay between malignant and host cells. The perioperative period represents an underutilized window of opportunity for cancer treatment where tumor-host interactions can be modulated, reducing the risk of local recurrences and distant metastases. Blood-saving agents are attractive compounds to be administered during tumor surgery. Desmopressin (DDAVP) is a safe and convenient hemostatic peptide with proved antimetastastic properties in experimental models and veterinary clinical trials. The compound seems to induce a dual angiostatic and antimetastatic effect, breaking the cooperative function of cancer cells and endothelial cells during residual tumor progression. DDAVP is therefore an interesting lead compound to develop novel synthetic peptide analogs with enhanced antitumor properties.

In silico modification of Zn2+ binding group of suberoylanilide hydroxamic acid (SAHA) by organoselenium compounds as Homo sapiens class II HDAC inhibitor of cervical cancer

Science.gov (United States)

Sumo Friend Tambunan, Usman; Bakri, Ridla; Aditya Parikesit, Arli; Ariyani, Titin; Dyah Puspitasari, Ratih; Kerami, Djati

2016-02-01

Cervical cancer is the most common cancer in women, and ranks seventh of all cancers worldwide, with 529000 cases in 2008 and more than 85% cases occur in developing countries. One way to treat this cancer is through the inhibition of HDAC enzymes which play a strategic role in the regulation of gene expression. Suberoyl Anilide Hydroxamic Acid (SAHA) or Vorinostat is a drug which commercially available to treat the cancer, but still has some side effects. This research present in silico SAHA modification in Zinc Binding Group (ZBG) by organoselenium compound to get ligands which less side effect. From molecular docking simulation, and interaction analysis, there are five best ligands, namely CC27, HA27, HB28, IB25, and KA7. These five ligands have better binding affinity than the standards, and also have interaction with Zn2+ cofactor of inhibited HDAC enzymes. This research is expected to produce more potent HDAC inhibitor as novel drug for cervical cancer treatment.

Review and research analysis of computational target methods using BioRuby and in silico screening of herbal lead compounds against pancreatic cancer using R programming.

Science.gov (United States)

Jayadeepa, R M; Ray, Ankita; Naik, Dhaval; Sanyal, Debendra Nath; Shah, Disha

2014-01-01

Plants and their natural components sophisticated with the cornerstone of traditional conventional medicinal system throughout the globe for many years and extend to furnish mankind with latest remedies. Natural Products act as lead molecules for the synthesis of various potent drugs. In the current research a study is conducted on herbal small molecule and their potential binding chemical affinity to the effect or molecules of major diseases such as pancreatic cancer. Clinical studies demonstrate correlation between Cyclin- Dependent Kinase 4 (CDK4) and malignant progression of Pancreatic Cancer. Using Bioruby Gem's we were able to analyze better characteristics of the target protein. VegaZZ and NAMD were used to minimize the energy of the target protein. Therefore identification of effective, well- tolerated targets was analyzed. Further the target protein was subjected to docking with the anti cancer inhibitors which represents a rational chemo preventive strategy using AutoDock Vina. Later using the dock score top ranked phytochemicals were analyzed for Toxicity Analysis. Using the BioRuby gem we were able to measure the distance between the amino acid. Various R scripting libraries were used to hunt the best leads, as in this case the phytochemicals. Phytochemicals such as Wedelolactones and Catechin were analyzed computationally. This study has presented the various effects of naturally occurring anti pancreatic cancer compounds Catechin, Wedelolactones that inhibits Cyclin Dependent Kinase 4. The study results reveal that compounds use less binding energy to CDK4 and inhibit its activity. Future investigation of other various wet lab studies such as cell line studies will confirm results of these two herbal chemical formulations potential ones for treating Pancreatic Cancer.

Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions

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Eugene B. Chang

2013-01-01

Full Text Available Compound K (20-O-beta-D-glucopyranosyl-20(S-protopanaxadiol, CK, an intestinal bacterial metabolite of ginseng protopanaxadiol saponins, has been shown to inhibit cell growth in a variety of cancers. However, the mechanisms are not completely understood, especially in colorectal cancer (CRC. A xenograft tumor model was used first to examine the anti-CRC effect of CK in vivo. Then, multiple in vitro assays were applied to investigate the anticancer effects of CK including antiproliferation, apoptosis and cell cycle distribution. In addition, a qPCR array and western blot analysis were executed to screen and validate the molecules and pathways involved. We observed that CK significantly inhibited the growth of HCT-116 tumors in an athymic nude mouse xenograft model. CK significantly inhibited the proliferation of human CRC cell lines HCT-116, SW-480, and HT-29 in a dose- and time-dependent manner. We also observed that CK induced cell apoptosis and arrested the cell cycle in the G1 phase in HCT-116 cells. The processes were related to the upregulation of p53/p21, FoxO3a-p27/p15 and Smad3, and downregulation of cdc25A, CDK4/6 and cyclin D1/3. The major regulated targets of CK were cyclin dependent inhibitors, including p21, p27, and p15. These results indicate that CK inhibits transcriptional activation of multiple tumor-promoting pathways in CRC, suggesting that CK could be an active compound in the prevention or treatment of CRC.

New Approaches for the Synthesis, Cytotoxicity and Toxicity of Heterocyclic Compounds Derived from 2-Cyanomethylbenzo[c]imidazole.

Science.gov (United States)

Mohareb, Rafat M; Mohamed, Abeer A; Abdallah, Amira E M

2016-01-01

The reaction of ethyl cyanoacetate with o-phenylenediamine gave the 2-cyanomethylbenzo[c]imidazole (1). The latter compound was used as the key starting material to synthesise biologically active heterocyclic derivatives. Thus, the reaction of 1 with cyclohexanone and either of benzaldehyde, 4-methoxybenzaldehyde or 4-chlorobenzaldehyde gave the annulated derivatives 2a-c, respectively. The antitumor evaluations of the newly synthesized products against the three cancer cell lines MCF-7 (breast adeno-carcinoma), NCI-H460 (non-small cell lung cancer) and SF-268 (CNS cancer) showed that compounds 2b, 6, 11b, 11c, 12b, 16a, 16b and 18a exhibited optimal cytotoxic effect against cancer cell lines, with IC50 values in the nM range. Bioactive compounds are often toxic to shrimp larvae. Thus, in order to monitor these chemicals in vivo lethality to shrimp larvae (Artemia salina), Brine-Shrimp Lethality Assay was used. Compounds 11b, 12b and 16b showed no toxicity against the tested organisms.

The ethanol extract of Scutellaria baicalensis and the active compounds induce cell cycle arrest and apoptosis including upregulation of p53 and Bax in human lung cancer cells

International Nuclear Information System (INIS)

Gao Jiayu; Morgan, Winston A.; Sanchez-Medina, Alberto; Corcoran, Olivia

2011-01-01

Despite a lack of scientific authentication, Scutellaria baicalensis is clinically used in Chinese medicine as a traditional adjuvant to chemotherapy of lung cancer. In this study, cytotoxicity assays demonstrated that crude ethanolic extracts of S. baicalensis were selectively toxic to human lung cancer cell lines A549, SK-LU-1 and SK-MES-1 compared with normal human lung fibroblasts. The active compounds baicalin, baicalein and wogonin did not exhibit such selectivity. Following exposure to the crude extracts, cellular protein expression in the cancer cell lines was assessed using 2D gel electrophoresis coupled with MALDI-TOF-MS/Protein Fingerprinting. The altered protein expression indicated that cell growth arrest and apoptosis were potential mechanisms of cytotoxicity. These observations were supported by PI staining cell cycle analysis using flow cytometry and Annexin-V apoptotic analysis by fluorescence microscopy of cancer cells treated with the crude extract and pure active compounds. Moreover, specific immunoblotting identification showed the decreased expression of cyclin A results in the S phase arrest of A549 whereas the G 0 /G 1 phase arrest in SK-MES-1 cells results from the decreased expression of cyclin D1. Following treatment, increased expression in the cancer cells of key proteins related to the enhancement of apoptosis was observed for p53 and Bax. These results provide further insight into the molecular mechanisms underlying the clinical use of this herb as an adjuvant to lung cancer therapy. - Research highlights: → Scutellaria baicalensis is a clinical adjuvant to lung cancer chemotherapy in China. → Scutellaria ethanol extracts selectively toxic to A549, SK-LU-1 and SK-MES-1. → Baicalin, baicalein and wogonin were toxic to all lung cancer cell lines. → Proteomics identified increased p53 and BAX in response to Scutellaria extracts.

Effect of perioperative application of L-asrginine combined with intacted protein compound preparations on postoperative antitumor immunity and tumor load in patients with gastric cancer

Directory of Open Access Journals (Sweden)

Xiu-Lan Jiang

2016-10-01

Full Text Available Objective: To analyze the effect of perioperative application of L-arginine combined with intacted protein compound preparations on postoperative antitumor immunity and tumor load in patients with gastric cancer. Methods: A total of 68 patients with gastric cancer received radical operation, and according to different perioperative nutrition intervention, they were divided into control group (normal glucose saline enteral nutrition and observation group (L-arginine combined with intacted protein compound preparations enteral nutrition by half. Postoperative short-term antitumor immune cell levels and serum levels of illness-related indexes, nutrition and inflammation indexes of two groups were detected, patients were followed up for 3 years and the gastric stump MRI changes were observed. Results: Venous blood CD4+ T lymphocyte level and CD4+ /CD8+ ratio of observation group 3 months after treatment were higher than those of control group while CD8+ T lymphocyte and Treg cell levels were lower than those of control group; serum Pentraxin-3, CYFRA21-1, TTF-1 and HE4 levels were lower than those of control group; ALB, PA and IL-2 levels were higher than those of control group while IL-6 and IL-10 levels were lower than those of control group (P<0.05. Gastric stump MRI images 3 years after operation were significantly different between two groups. Conclusions: Perioperative application of L-arginine combined with intacted protein compound preparations can optimize postoperative immune and nutritional state in patients with gastric cancer, and it also has positive effect on reducing the incidence of long-term gastric stump carcinoma and other aspects.

A Multiplexed Assay That Monitors Effects of Multiple Compound Treatment Times Reveals Candidate Immune-Enhancing Compounds.

Science.gov (United States)

Zhao, Ziyan; Henowitz, Liza; Zweifach, Adam

2018-05-01

We previously developed a flow cytometry assay that monitored lytic granule exocytosis in cytotoxic T lymphocytes stimulated by contacting beads coated with activating anti-CD3 antibodies. That assay was multiplexed in that responses of cells that did or did not receive the activating stimulus were distinguished via changes in light scatter accompanying binding of cells to beads, allowing us to discriminate compounds that activate responses on their own from compounds that enhance responses in cells that received the activating stimulus, all within a single sample. Here we add a second dimension of multiplexing by developing means to assess in a single sample the effects of treating cells with test compounds for different times. Bar-coding cells before adding them to test wells lets us determine compound treatment time while also monitoring activation status and response amplitude at the point of interrogation. This multiplexed assay is suitable for screening 96-well plates. We used it to screen compounds from the National Cancer Institute, identifying several compounds that enhance anti-LAMP1 responses. Multiple-treatment-time (MTT) screening enabled by bar-coding and read via high-throughput flow cytometry may be a generally useful method for facilitating the discovery of compounds of interest.

Pectolinarigenin - A Flavonoid Compound from Cirsium Japonicum ...

African Journals Online (AJOL)

HP

/tjpr.v13i2.9. Original Research Article. Pectolinarigenin - A Flavonoid Compound from Cirsium. Japonicum with Potential Anti-proliferation Activity in MCF-. 7 Breast Cancer Cell. Mingqian Lu. 1,2,3. , Qingzhi Kong. 1,4. *, Xinhua Xu. 2,3.

Quo natas, Danio?—Recent Progress in Modeling Cancer in Zebrafish

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Stefanie Kirchberger

2017-08-01

Full Text Available Over the last decade, zebrafish has proven to be a powerful model in cancer research. Zebrafish form tumors that histologically and genetically resemble human cancers. The live imaging and cost-effective compound screening possible with zebrafish especially complement classic mouse cancer models. Here, we report recent progress in the field, including genetically engineered zebrafish cancer models, xenotransplantation of human cancer cells into zebrafish, promising approaches toward live investigation of the tumor microenvironment, and identification of therapeutic strategies by performing compound screens on zebrafish cancer models. Given the recent advances in genome editing, personalized zebrafish cancer models are now a realistic possibility. In addition, ongoing automation will soon allow high-throughput compound screening using zebrafish cancer models to be part of preclinical precision medicine approaches.

Five new compounds from the fungus Ganoderma petchii.

Science.gov (United States)

Dai, Wei-Feng; Guo, Ping-Xia; Tu, Zheng-Chao; Li, Rong-Tao; Cheng, Yong-Xian

2015-10-01

The fungal species of the genus Ganoderma attracted great interest in the last decades. Our recent investigation on Ganoderma petchii afforded five new compounds, (-)-petchioics A and B (1 and 2), petchiates A and B (3 and 4), petchine (5), and a known compound. The structures of the new compounds were elucidated on the basis of spectroscopic data. The absolute configurations of 1 and 2 were assigned by computational methods. Biological activities of these isolates towards human cancer cells, COX-1/2, and influenza virus were evaluated. Copyright © 2015 Elsevier B.V. All rights reserved.

Basic study on a diagnostic method for breast cancer using a novel radio-labelled compound and the therapeutic method with it

International Nuclear Information System (INIS)

Ikebuchi, Hideharu; Saito, Yoshiro; Tanaka, Toichi; Tejima, Reiko; Sawada, Junichi

1999-01-01

In the previous studies of this project, binding activities and growth inhibitory effects of estrogen-related compounds (EC) were investigated in breast cancer cell lines, FCM-7 and MDA-MS-231. It was shown that EC such as 2-hydroxy estron, 2-hydroxy estrogen and estrogen significantly inhibited the growth of these cells and had highly binding activities to their estrogen receptors. Here, an investigation was made on the involvement of these compounds in intracellular signaling pathways. Mitogen activated protein (MAP)-kinase cascade is regarded as one of the important intracellular signaling pathways and MAPK-kinase positioned at the most downstream region has been known to migrate from cytoplasm to the nucleus associating with progressing of a cell growth and differentiation. So, correlation of MAP-kinase with the binding activity of ERC onto breast cells or with the growth repression was investigated. Since it has been shown that MAP.- and MAPK-kinase were activated in FCM-7 cells cultured with EGF, the binding activity of ERC was assessed in the presence of EGF. The binding activities to FCM-7 cells were, however, not affected by the addition of MAP-kinase. Although significant growth inhibitory effects of 2-hydroxy estron and 2-hydroxy estrogen on FCM-7 cells were confirmed as shown in the previous study, either of treatment with PD98059, an inhibitor for MAPK-kinase or expression of MKP3, a specific phosphatase for MAPK-kinase caused a repression of cell growth. These results suggest that MAP-kinase might be involved in the growth of breast cancer cells and cancer cell growth would be also affected by activation of MAP-kinase cascade. (M.N.)

SU-E-T-225: Correction Matrix for PinPoint Ionization Chamber for Dosimetric Measurements in the Newly Released Incise™ Multileaf Collimator Shaped Small Field for CyberKnife M6™ Machine

Energy Technology Data Exchange (ETDEWEB)

Zhang, Y; Li, T; Heron, D; Huq, M [University of Pittsburgh Cancer Institute and UPMC CancerCenter, Pittsburgh, PA (United States)

2015-06-15

Purpose: For small field dosimetry, such as measurements of output factors for cones or MLC-shaped irregular small fields, ion chambers often Result in an underestimation of the dose, due to both the volume averaging effect and the lack of lateral charged particle equilibrium. This work presents a mathematical model for correction matrix for a PTW PinPoint ionization chamber for dosimetric measurements made in the newly released Incise™ Multileaf collimator fields of the CyberKnife M6™ machine. Methods: A correction matrix for a PTW 0.015cc PinPoint ionization chamber was developed by modeling its 3D dose response in twelve cone-shaped circular fields created using the 5mm, 7.5mm, 10mm, 12.5mm, 15mm, 20mm, 25mm, 30mm, 35mm, 40mm, 50mm, 60mm cones in a CyberKnife M6™ machine. For each field size, hundreds of readings were recorded for every 2mm chamber shift in the horizontal plane. The contribution of each dose pixel to a measurement point depended on the radial distance and the angle to the chamber axis. These readings were then compared with the theoretical dose as obtained with Monte Carlo calculation. A penalized least-square optimization algorithm was developed to generate the correction matrix. After the parameter fitting, the mathematical model was validated for MLC-shaped irregular fields. Results: The optimization algorithm used for parameter fitting was stable and the resulted response factors were smooth in spatial domain. After correction with the mathematical model, the chamber reading matched with the calculation for all the tested fields to within 2%. Conclusion: A novel mathematical model has been developed for PinPoint chamber for dosimetric measurements in small MLC-shaped irregular fields. The correction matrix is dependent on detector, treatment unit and the geometry of setup. The model can be applied to non-standard composite fields and provides an access to IMRT point dose validation.

SU-E-T-225: Correction Matrix for PinPoint Ionization Chamber for Dosimetric Measurements in the Newly Released Incise™ Multileaf Collimator Shaped Small Field for CyberKnife M6™ Machine

International Nuclear Information System (INIS)

Zhang, Y; Li, T; Heron, D; Huq, M

2015-01-01

Purpose: For small field dosimetry, such as measurements of output factors for cones or MLC-shaped irregular small fields, ion chambers often Result in an underestimation of the dose, due to both the volume averaging effect and the lack of lateral charged particle equilibrium. This work presents a mathematical model for correction matrix for a PTW PinPoint ionization chamber for dosimetric measurements made in the newly released Incise™ Multileaf collimator fields of the CyberKnife M6™ machine. Methods: A correction matrix for a PTW 0.015cc PinPoint ionization chamber was developed by modeling its 3D dose response in twelve cone-shaped circular fields created using the 5mm, 7.5mm, 10mm, 12.5mm, 15mm, 20mm, 25mm, 30mm, 35mm, 40mm, 50mm, 60mm cones in a CyberKnife M6™ machine. For each field size, hundreds of readings were recorded for every 2mm chamber shift in the horizontal plane. The contribution of each dose pixel to a measurement point depended on the radial distance and the angle to the chamber axis. These readings were then compared with the theoretical dose as obtained with Monte Carlo calculation. A penalized least-square optimization algorithm was developed to generate the correction matrix. After the parameter fitting, the mathematical model was validated for MLC-shaped irregular fields. Results: The optimization algorithm used for parameter fitting was stable and the resulted response factors were smooth in spatial domain. After correction with the mathematical model, the chamber reading matched with the calculation for all the tested fields to within 2%. Conclusion: A novel mathematical model has been developed for PinPoint chamber for dosimetric measurements in small MLC-shaped irregular fields. The correction matrix is dependent on detector, treatment unit and the geometry of setup. The model can be applied to non-standard composite fields and provides an access to IMRT point dose validation

Anti-cancer activities of diospyrin, its derivatives and analogues

KAUST Repository

Sagar, Sunil; Kaur, Mandeep; Minneman, Kenneth P.; Bajic, Vladimir B.

2010-01-01

Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

Anti-cancer activities of diospyrin, its derivatives and analogues

KAUST Repository

Sagar, Sunil

2010-09-01

Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

Anticancer Effects of Different Seaweeds on Human Colon and Breast Cancers

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Ghislain Moussavou

2014-09-01

Full Text Available Seafoods and seaweeds represent some of the most important reservoirs of new therapeutic compounds for humans. Seaweed has been shown to have several biological activities, including anticancer activity. This review focuses on colorectal and breast cancers, which are major causes of cancer-related mortality in men and women. It also describes various compounds extracted from a range of seaweeds that have been shown to eradicate or slow the progression of cancer. Fucoidan extracted from the brown algae Fucus spp. has shown activity against both colorectal and breast cancers. Furthermore, we review the mechanisms through which these compounds can induce apoptosis in vitro and in vivo. By considering the ability of compounds present in seaweeds to act against colorectal and breast cancers, this review highlights the potential use of seaweeds as anticancer agents.

Anticancer activity of botanical compounds in ancient fermented beverages (review).

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McGovern, P E; Christofidou-Solomidou, M; Wang, W; Dukes, F; Davidson, T; El-Deiry, W S

2010-07-01

Humans around the globe probably discovered natural remedies against disease and cancer by trial and error over the millennia. Biomolecular archaeological analyses of ancient organics, especially plants dissolved or decocted as fermented beverages, have begun to reveal the preliterate histories of traditional pharmacopeias, which often date back thousands of years earlier than ancient textual, ethnohistorical, and ethnological evidence. In this new approach to drug discovery, two case studies from ancient Egypt and China illustrate how ancient medicines can be reconstructed from chemical and archaeological data and their active compounds delimited for testing their anticancer and other medicinal effects. Specifically, isoscopoletin from Artemisia argyi, artemisinin from Artemisia annua, and the latter's more easily assimilated semi-synthetic derivative, artesunate, showed the greatest activity in vitro against lung and colon cancers. In vivo tests of these compounds previously unscreened against lung and pancreatic cancers are planned for the future.

Sea cucumbers, the ocean of bioactive compounds

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Hadi Ebrahimi

2015-07-01

Full Text Available Sea cucumbers are one of the most echinoderms and from the class Holothuroidea. Some of their specific biological activities are including anti-cancer, anticoagulant, antihypertensive, anti-inflammatory, antimicrobial, antioxidant, anti-atherosclerosis and anti-tumor properties, as well as accelerate wound healing. The presence of different compounds such as saponins, chondroitin sulfates, glycosaminoglycans, sulfated Polysaccharides, glycoprotein, glycosphingolipids and essential and non essential fatty acids, are the causes of their biological properties. Saponins, which are produced for compatibility with the environment, are as theire secondary metabolites. These active compounds have biological properties like hemolytic, anti-tumor, anti-inflammatory, antibacterial, antiviral, ichthyotoxic, cytostatic, anti neogenic, antineoplastic, and uric acid lowering effects. Sea cucumber, have high economic value. In East Asia, Since ancient times, it have been traditionally used for the treatment of fatigue, sexual impotence, impotence caused by aging, constipation due to intestinal dryness, urinary incontinence, asthma, hypertension, arthritis and anemia. Also, toxins obtained from sea cucumber, have anti-viral, anti-tumor, anti-cancer and anti-pregnancy properties. According to literatures, the aqueous extract and high molecular weight compounds from sea cucumbers can inhibit tumor activity, via the apoptosis induction. Sea cucumbers because of the high percentage of protein and the absence of cholesterol, classified as an invigorating food. Because of different species of sea cucumbers in the Persian Gulf and Oman Sea the identification of compounds and biological properties of sea cucumber species in these regions is recommended to the researchers.

Comparison of Multiple Linear Regressions and Neural Networks based QSAR models for the design of new antitubercular compounds.

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Ventura, Cristina; Latino, Diogo A R S; Martins, Filomena

2013-01-01

The performance of two QSAR methodologies, namely Multiple Linear Regressions (MLR) and Neural Networks (NN), towards the modeling and prediction of antitubercular activity was evaluated and compared. A data set of 173 potentially active compounds belonging to the hydrazide family and represented by 96 descriptors was analyzed. Models were built with Multiple Linear Regressions (MLR), single Feed-Forward Neural Networks (FFNNs), ensembles of FFNNs and Associative Neural Networks (AsNNs) using four different data sets and different types of descriptors. The predictive ability of the different techniques used were assessed and discussed on the basis of different validation criteria and results show in general a better performance of AsNNs in terms of learning ability and prediction of antitubercular behaviors when compared with all other methods. MLR have, however, the advantage of pinpointing the most relevant molecular characteristics responsible for the behavior of these compounds against Mycobacterium tuberculosis. The best results for the larger data set (94 compounds in training set and 18 in test set) were obtained with AsNNs using seven descriptors (R(2) of 0.874 and RMSE of 0.437 against R(2) of 0.845 and RMSE of 0.472 in MLRs, for test set). Counter-Propagation Neural Networks (CPNNs) were trained with the same data sets and descriptors. From the scrutiny of the weight levels in each CPNN and the information retrieved from MLRs, a rational design of potentially active compounds was attempted. Two new compounds were synthesized and tested against M. tuberculosis showing an activity close to that predicted by the majority of the models. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Synthesis, SAR and pharmacological characterization of novel anthraquinone cation compounds as potential anticancer agents.

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Zheng, Yanyan; Zhu, Li; Fan, Lulu; Zhao, Wenna; Wang, Jianlong; Hao, Xianxiao; Zhu, Yunhui; Hu, Xiufang; Yuan, Yaofeng; Shao, Jingwei; Wang, Wenfeng

2017-01-05

Emodin, a natural anthraquinone derivative isolated from Rheum palmatum L., has been demonstrated to exhibit good anti-cancer effect. In this study, a series of novel quaternary ammonium salts of emodin, anthraquinone and anthrone were synthesized and their anticancer activities were tested in vitro. The effects of emodin quaternary ammonium salts on cell viability, apoptosis, intracellular ROS, and mitochondrial membrane potential were investigated in A375, BGC-823, HepG2 and HELF cells. The results demonstrated that compound 4a induced morphological changes and decreased cell viability. Apoptosis triggered by compound 4a was visualized using DAPI staining and Annexin V-FITC/PI staining. Compound 4a-induced apoptosis of A375 cells were showed to be associated with the dissipation of mitochondrial membrane potential (ΔΨm) as a result of the up-regulation of P53 and Caspase-3. When cancer cells were treated with emodin derivative, their ability to generate reactive oxygen species (ROS) rose significantly and the mitochondrial membrane potential decreased. Additionally, confocal microscopy assay confirmed that compound 4a was primarily located in the mitochondria of A375 cells. These results suggested that compound 4a has the potential for use in cancer therapy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Vanadium Compounds as PTP Inhibitors

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Elsa Irving

2017-12-01

Full Text Available Phosphotyrosine signaling is regulated by the opposing actions of protein tyrosine kinases (PTKs and protein tyrosine phosphatases (PTPs. Here we discuss the potential of vanadium derivatives as PTP enzyme inhibitors and metallotherapeutics. We describe how vanadate in the V oxidized state is thought to inhibit PTPs, thus acting as a pan-inhibitor of this enzyme superfamily. We discuss recent developments in the biological and biochemical actions of more complex vanadium derivatives, including decavanadate and in particular the growing number of oxidovanadium compounds with organic ligands. Pre-clinical studies involving these compounds are discussed in the anti-diabetic and anti-cancer contexts. Although in many cases PTP inhibition has been implicated, it is also clear that many such compounds have further biochemical effects in cells. There also remain concerns surrounding off-target toxicities and long-term use of vanadium compounds in vivo in humans, hindering their progress through clinical trials. Despite these current misgivings, interest in these chemicals continues and many believe they could still have therapeutic potential. If so, we argue that this field would benefit from greater focus on improving the delivery and tissue targeting of vanadium compounds in order to minimize off-target toxicities. This may then harness their full therapeutic potential.

Vitamin D in prostate cancer

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Donald L Trump

2018-01-01

Full Text Available Signaling through the vitamin D receptor has been shown to be biologically active and important in a number of preclinical studies in prostate and other cancers. Epidemiologic data also indicate that vitamin D signaling may be important in the cause and prognosis of prostate and other cancers. These data indicate that perturbation of vitamin D signaling may be a target for the prevention and treatment of prostate cancer. Large studies of vitamin D supplementation will be required to determine whether these observations can be translated into prevention strategies. This paper reviews the available data in the use of vitamin D compounds in the treatment of prostate cancer. Clinical data are limited which support the use of vitamin D compounds in the management of men with prostate cancer. However, clinical trials guided by existing preclinical data are limited.

Vitamin D in prostate cancer.

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Trump, Donald L; Aragon-Ching, Jeanny B

2018-04-13

Signaling through the vitamin D receptor has been shown to be biologically active and important in a number of preclinical studies in prostate and other cancers. Epidemiologic data also indicate that vitamin D signaling may be important in the cause and prognosis of prostate and other cancers. These data indicate that perturbation of vitamin D signaling may be a target for the prevention and treatment of prostate cancer. Large studies of vitamin D supplementation will be required to determine whether these observations can be translated into prevention strategies. This paper reviews the available data in the use of vitamin D compounds in the treatment of prostate cancer. Clinical data are limited which support the use of vitamin D compounds in the management of men with prostate cancer. However, clinical trials guided by existing preclinical data are limited.

Vitamin D in prostate cancer

Science.gov (United States)

Trump, Donald L; Aragon-Ching, Jeanny B

2018-01-01

Signaling through the vitamin D receptor has been shown to be biologically active and important in a number of preclinical studies in prostate and other cancers. Epidemiologic data also indicate that vitamin D signaling may be important in the cause and prognosis of prostate and other cancers. These data indicate that perturbation of vitamin D signaling may be a target for the prevention and treatment of prostate cancer. Large studies of vitamin D supplementation will be required to determine whether these observations can be translated into prevention strategies. This paper reviews the available data in the use of vitamin D compounds in the treatment of prostate cancer. Clinical data are limited which support the use of vitamin D compounds in the management of men with prostate cancer. However, clinical trials guided by existing preclinical data are limited. PMID:29667615

Perspectives of antimony compounds in oncology

Institute of Scientific and Technical Information of China (English)

Pankaj SHARMA; Diego PEREZ; Armando CABRERA; Nee ROSAS; Jose Luis ARIAS

2008-01-01

Antimony, a natural element that has been used as a drug for over more than 100 years, has remarkable therapeutic efficacy in patients with acute promyelocytic leukemia. This review focuses on recent advances in developing antimony anti- cancer agents with an emphasis on antimony coordination complexes, Sb (Ⅲ) and Sb (V). These complexes, which include many organometallic complexes, may provide a broader spectrum of antitumoral activity. They were compared with classical platinum anticancer drugs. The review covers the literature data pub- lished up to 2007. A number of antimonials with different antitumoral activities are known and have diverse applications, even though little research has been done on their possibilities. It might be feasible to develop more specific and effective inhibitors for phosphatase-targeted, anticancer therapeutics through the screen- ing of sodium stibogluconate (SSG) and potassium antimonyltartrate-related compounds, which are comprised of antimony conjugated to different organic moieties. For example, SSG appears to be a better inhibitor than suramin which is a compound known for its antineoplastic activity against several types of cancers.

Metabolic cooperation between cancer and non-cancerous stromal cells is pivotal in cancer progression.

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Lopes-Coelho, Filipa; Gouveia-Fernandes, Sofia; Serpa, Jacinta

2018-02-01

The way cancer cells adapt to microenvironment is crucial for the success of carcinogenesis, and metabolic fitness is essential for a cancer cell to survive and proliferate in a certain organ/tissue. The metabolic remodeling in a tumor niche is endured not only by cancer cells but also by non-cancerous cells that share the same microenvironment. For this reason, tumor cells and stromal cells constitute a complex network of signal and organic compound transfer that supports cellular viability and proliferation. The intensive dual-address cooperation of all components of a tumor sustains disease progression and metastasis. Herein, we will detail the role of cancer-associated fibroblasts, cancer-associated adipocytes, and inflammatory cells, mainly monocytes/macrophages (tumor-associated macrophages), in the remodeling and metabolic adaptation of tumors.

Ukrain, a plant derived semi-synthetic compound, exerts antitumor effects against murine and human breast cancer and induce protective antitumor immunity in mice.

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Bozeman, E N; Srivatsan, S; Mohammadi, H; Daniels, D; Shashidharamurthy, R; Selvaraj, P

2012-12-01

Despite the recent advances in anti-cancer therapies, breast cancer accounts for the highest percentage of estimated new cases among female cancer patients. The anti-cancer drug Ukrain, a plant-derived semi-synthetic compound, has been shown to be effective in a variety of tumor models including colon, brain, ovarian, melanoma and lymphoma. However, the direct cytotoxic effects of Ukrain have yet to be investigated in breast cancer models. Herein, we investigated the in vitro and in vivo cytotoxicity of Ukrain using murine (4T07 and TUBO) and human (SKBR-3) breast cancer cell lines. Cells were treated with varying concentrations of Ukrain for up to 72 h and analyzed for viability by trypan blue exclusion, apoptosis by intracellular caspase 3 and Annexin V staining, and proliferative potential by a clonogenic assay. Female BALB/c mice were challenged subcutaneously (s.c.) with 4T07-RG cells and administered 5 mg/kg or 12.5 mg/kg body weight Ukrain intravenously (i.v.) on the same day and 3 days later. Protective immune responses were determined following re-challenge of tumor-free mice 35 days post primary challenge. Ukrain exposure induced apoptosis in a dose and time-dependent manner with 50 µg/mL Ukrain leading to >50% cell death after 48 h exposure for all three breast cancer cell lines. Ukrain administration (12.5 mg/kg) led to significant inhibition of 4T07 tumor growth in vivo and sustained protective anti-tumor immunity following secondary challenge. Our findings demonstrate the in vitro and in vivo cytotoxic effects of Ukrain on breast cancer cells and may provide insight into designing Ukrain-based therapies for breast cancer patients.

Auraptene, a Major Compound of Supercritical Fluid Extract of Phalsak (Citrus Hassaku Hort ex Tanaka, Induces Apoptosis through the Suppression of mTOR Pathways in Human Gastric Cancer SNU-1 Cells

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Jeong Yong Moon

2015-01-01

Full Text Available The supercritical extraction method is a widely used process to obtain volatile and nonvolatile compounds by avoiding thermal degradation and solvent residue in the extracts. In search of phytochemicals with potential therapeutic application in gastric cancer, the supercritical fluid extract (SFE of phalsak (Citrus hassaku Hort ex Tanaka fruits was analyzed by gas chromatography-mass spectrometry (GC-MS. Compositional analysis in comparison with the antiproliferative activities of peel and flesh suggested auraptene as the most prominent anticancer compound against gastric cancer cells. SNU-1 cells were the most susceptible to auraptene-induced toxicity among the tested gastric cancer cell lines. Auraptene induced the death of SNU-1 cells through apoptosis, as evidenced by the increased cell population in the sub-G1 phase, the appearance of fragmented nuclei, the proteolytic cleavage of caspase-3 and poly(ADP-ribose polymerase (PARP protein, and depolarization of the mitochondrial membrane. Interestingly, auraptene induces an increase in the phosphorylation of Akt, which is reminiscent of the effect of rapamycin, the mTOR inhibitor that triggers a negative feedback loop on Akt/mTOR pathway. Taken together, these findings provide valuable insights into the anticancer effects of the SFE of the phalsak peel by revealing that auraptene, the major compound of it, induced apoptosis in accompanied with the inhibition of mTOR in SNU-1 cells.

African medicinal plants and their derivatives: Current efforts towards potential anti-cancer drugs.

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Mbele, Mzwandile; Hull, Rodney; Dlamini, Zodwa

2017-10-01

Cancer is a leading cause of mortality and morbidity worldwide and second only to cardiovascular diseases. Cancer is a challenge in African countries because generally there is limited funding available to deal with the cancer epidemic and awareness and this should be prioritised and all possible resources should be utilized to prevent and treat cancer. The current review reports on the role of African medicinal plants in the treatment of cancer, and also outlines methodologies that can also be used to achieve better outcomes for cancer treatment. This review outlines African medicinal plants, isolated compounds and technologies that can be used to advance cancer research. Chemical structures of isolated compounds have an important role in anti-cancer treatments; new technologies and methods may assist to identify more properties of African medicinal plants and the treatment of cancer. In conclusion, African medicinal plants have shown their potential as enormous resources for novel cytotoxicity compounds. Finally it has been noted that the cytotoxicity depends on the chemical structural arrangements of African medicinal plants compounds. Copyright © 2017 Elsevier Inc. All rights reserved.

Nesting of colon and ovarian cancer cells in the endothelial niche is associated with alterations in glycan and lipid metabolism.

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Halama, Anna; Guerrouahen, Bella S; Pasquier, Jennifer; Satheesh, Noothan J; Suhre, Karsten; Rafii, Arash

2017-01-04

The metabolic phenotype of a cancer cell is determined by its genetic makeup and microenvironment, which dynamically modulates the tumor landscape. The endothelial cells provide both a promoting and protective microenvironment - a niche for cancer cells. Although metabolic alterations associated with cancer and its progression have been fairly defined, there is a significant gap in our understanding of cancer metabolism in context of its microenvironment. We deployed an in vitro co-culture system based on direct contact of cancer cells with endothelial cells (E4 + EC), mimicking the tumor microenvironment. Metabolism of colon (HTC15 and HTC116) and ovarian (OVCAR3 and SKOV3) cancer cell lines was profiled with non-targeted metabolic approaches at different time points in the first 48 hours after co-culture was established. We found significant, coherent and non-cell line specific changes in fatty acids, glycerophospholipids and carbohydrates over time, induced by endothelial cell contact. The metabolic patterns pinpoint alterations in hexosamine biosynthetic pathway, glycosylation and lipid metabolism as crucial for cancer - endothelial cells interaction. We demonstrated that "Warburg effect" is not modulated in the initial stage of nesting of cancer cell in the endothelial niche. Our study provides novel insight into cancer cell metabolism in the context of the endothelial microenvironment.

Targeting Sonic Hedgehog Signaling by Compounds and Derivatives from Natural Products

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Yu-Chuen Huang

2013-01-01

Full Text Available Cancer stem cells (CSCs are a major cause of cancer treatment failure, relapse, and drug resistance and are known to be responsible for cancer cell invasion and metastasis. The Sonic hedgehog (Shh signaling pathway is crucial to embryonic development. Intriguingly, the aberrant activation of the Shh pathway plays critical roles in developing CSCs and leads to angiogenesis, migration, invasion, and metastasis. Natural compounds and chemical structure modified derivatives from complementary and alternative medicine have received increasing attention as cancer chemopreventives, and their antitumor effects have been demonstrated both in vitro and in vivo. However, reports for their bioactivity against CSCs and specifically targeting Shh signaling remain limited. In this review, we summarize investigations of the compounds cyclopamine, curcumin, epigallocatechin-3-gallate, genistein, resveratrol, zerumbone, norcantharidin, and arsenic trioxide, with a focus on Shh signaling blockade. Given that Shh signaling antagonism has been clinically proven as effective strategy against CSCs, this review may be exploitable for development of novel anticancer agents from complementary and alternative medicine.

Virtual Dual inhibition of COX-2 / 5-LOX enzymes based on binding properties of alpha-amyrins, the anti-inflammatory compound as a promising anti-cancer drug

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Ranjbar, Mohammad Mehdi; Assadolahi, Vahideh; Yazdani, Mohsen; Nikaein, Donya; Rashidieh, Behnam

2016-01-01

Hydro-alcoholic fruit extract of Cordia myxa was considerably effective on curing acute inflammation in mouse model. Previous studies suggested significant anti-inflammatory activities as well as potential anticancer agent of α-amyrins in seeds. Inhibition of Cyclooxygenase-2 (COX-2) and 5-Lipooxygenase (5-LOX) is significant in cancer prevention and therapeutics although this inhibition with chemo-drugs has its own side-effects. It is shown that these enzymes pathways are related to several cancers including colon, breast and lung cancer. This study was conducted based on Cordia species' α-amyrins as a safer natural anti-cancer compound for inhibition of COX-2 and 5-LOX enzymes by molecular docking. The X-ray crystal structure of COX2 / 5-LOX enzymes and α-amyrins was retrieved and energetically minimized respectively. The binding site and surface of enzymes were detected. Docking studies were performed by AutoDock 4.2 using Lamarckian genetic algorithm (LGA). Finally drug likeness, molecular pharmacokinetic properties and toxicity of α-amyrins was calculated. Molecular Docking revealed hydrogen and hydrophobic interactions between α-amyrins with both active sites of COX-2 and 5-LOX enzymes. Interestingly, it covalently bonded to Fe cofactor of 5-LOX enzyme and chelated this molecule. Base on binding energies (∆G) α-amyrin has more inhibitory effects on 5-LOX (-10.45 Kcal/mol) than COX-2 (-8.02 Kcal/mol). Analysis of molecular pharmacokinetic parameters suggested that α-amyrins complied with most sets of Lipinski's rules, and so it could be a suitable ligand for docking studies. Eventually, bioactivity score showed α-amyrins possess considerable biological activities as nuclear receptor, enzyme inhibitor, GPCR and protease inhibitor ligand. These results clearly demonstrate that α-amyrins could act as potential highly selective COX-/5-LOX inhibitor. Also, it is a safe compound in comparison with classical non-steroidal anti-inflammatory drugs (NSAIDs

Characterization of the apoptotic response of human leukemia cells to organosulfur compounds

International Nuclear Information System (INIS)

Wong, W Wei-Lynn; Langler, Richard F; Penn, Linda Z; Boutros, Paul C; Wasylishen, Amanda R; Guckert, Kristal D; O'Brien, Erin M; Griffiths, Rebecca; Martirosyan, Anna R; Bros, Christina; Jurisica, Igor

2010-01-01

Novel therapeutic agents that selectively induce tumor cell death are urgently needed in the clinical management of cancers. Such agents would constitute effective adjuvant approaches to traditional chemotherapy regimens. Organosulfur compounds (OSCs), such as diallyl disulfide, have demonstrated anti-proliferative effects on cancer cells. We have previously shown that synthesized relatives of dysoxysulfone, a natural OSC derived from the Fijian medicinal plant, Dysoxylum richi, possess tumor-specific antiproliferative effects and are thus promising lead candidates. Because our structure-activity analyses showed that regions flanking the disulfide bond mediated specificity, we synthesized 18 novel OSCs by structural modification of the most promising dysoxysulfone derivatives. These compounds were tested for anti-proliferative and apoptotic activity in both normal and leukemic cells. Six OSCs exhibited tumor-specific killing, having no effect on normal bone marrow, and are thus candidates for future toxicity studies. We then employed mRNA expression profiling to characterize the mechanisms by which different OSCs induce apoptosis. Using Gene Ontology analysis we show that each OSC altered a unique set of pathways, and that these differences could be partially rationalized from a transcription factor binding site analysis. For example, five compounds altered genes with a large enrichment of p53 binding sites in their promoter regions (p < 0.0001). Taken together, these data establish OSCs derivatized from dysoxysulfone as a novel group of compounds for development as anti-cancer agents

IRIS Toxicological Review of Thallium and Compounds ...

Science.gov (United States)

Thallium compounds are used in the semiconductor industry, the manufacture of optic lenses and low-melting glass, low-temperature thermometers, alloys, electronic devices, mercury lamps, fireworks, and imitation germs, and clinically as an imaging agent in the diagnosis of certain tumors. EPA's assessment of noncancer health effects and carcinogenic potential of thallium compounds was last prepared and added to the IRIS database between 1988 and 1990. The IRIS program is preparing an assessment that will incorporate current health effects information available for thallium and compounds, and current risk assessment methods. The IRIS assessment for thallium compounds will consist of a Toxicological Review and IRIS Summary. The Toxicological Review is a critical review of the physiochemical and toxicokinetic properties of a chemical, and its toxicity in humans and experimental systems. The assessment will present reference values for the noncancer effects of thallium compounds (RfD and Rfc), and a cancer assessment. The Toxicological Review and IRIS Summary have been subject to Agency review, Interagency review, and external scientific peer review. The final product will reflect the Agency opinion on the overall toxicity of thallium and compounds. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for thallium and compounds. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effec

Review of Pharmacological Effects of Antrodia camphorata and Its Bioactive Compounds

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Madamanchi Geethangili

2011-01-01

Full Text Available Antrodia camphorata is a unique mushroom of Taiwan, which has been used as a traditional medicine for protection of diverse health-related conditions. In an effort to translate this Eastern medicine into Western-accepted therapy, a great deal of work has been carried out on A. camphorata. This review discusses the biological activities of the crude extracts and the main bioactive compounds of A. camphorata. The list of bioactivities of crude extracts is huge, ranging from anti-cancer to vasorelaxation and others. Over 78 compounds consisting of terpenoids, benzenoids, lignans, benzoquinone derivatives, succinic and maleic derivatives, in addition to polysaccharides have been identified. Many of these compounds were evaluated for biological activity. Many activities of crude extracts and pure compounds of A. camphorata against some major diseases of our time, and thus, a current review is of great importance. It is concluded that A. camphorata can be considered as an efficient alternative phytotherapeutic agent or a synergizer in the treatment of cancer and other immune-related diseases. However, clinical trails of human on A. camphorata extracts are limited and those of pure compounds are absent. The next step is to produce some medicines from A. camphorata, however, the production may be hampered by problems related to mass production.

A fluorescence-based rapid screening assay for cytotoxic compounds

International Nuclear Information System (INIS)

Montoya, Jessica; Varela-Ramirez, Armando; Estrada, Abril; Martinez, Luis E.; Garza, Kristine; Aguilera, Renato J.

2004-01-01

A simple fluorescence-based assay was developed for the rapid screening of potential cytotoxic compounds generated by combinatorial chemistry. The assay is based on detection of nuclear green fluorescent protein (GFP) staining of a human cervical cancer cell line (HeLa) carrying an integrated histone H2B-GFP fusion gene. Addition of a cytotoxic compound to the HeLa-GFP cells results in the eventual degradation of DNA and loss of the GFP nuclear fluorescence. Using this assay, we screened 11 distinct quinone derivatives and found that several of these compounds were cytotoxic. These compounds are structurally related to plumbagin an apoptosis-inducing naphthoquinone isolated from Black Walnut. In order to determine the mechanism by which cell death was induced, we performed additional experiments with the most cytotoxic quinones. These compounds were found to induce morphological changes (blebbing and nuclear condensation) consistent with induction of apoptosis. Additional tests revealed that the cytotoxic compounds induce both necrotic and apoptotic modes of death

Marine Microalgae with Anti-Cancer Properties.

Science.gov (United States)

Martínez Andrade, Kevin A; Lauritano, Chiara; Romano, Giovanna; Ianora, Adrianna

2018-05-15

Cancer is the leading cause of death globally and finding new therapeutic agents for cancer treatment remains a major challenge in the pursuit for a cure. This paper presents an overview on microalgae with anti-cancer activities. Microalgae are eukaryotic unicellular plants that contribute up to 40% of global primary productivity. They are excellent sources of pigments, lipids, carotenoids, omega-3 fatty acids, polysaccharides, vitamins and other fine chemicals, and there is an increasing demand for their use as nutraceuticals and food supplements. Some microalgae are also reported as having anti-cancer activity. In this review, we report the microalgal species that have shown anti-cancer properties, the cancer cell lines affected by algae and the concentrations of compounds/extracts tested to induce arrest of cell growth. We also report the mediums used for growing microalgae that showed anti-cancer activity and compare the bioactivity of these microalgae with marine anticancer drugs already on the market and in phase III clinical trials. Finally, we discuss why some microalgae can be promising sources of anti-cancer compounds for future development.

1,1-Diphenyl-2-picrylhydrazyl radical-scavenging compounds from soybean miso and antiproliferative activity of isoflavones from soybean miso toward the cancer cell lines.

Science.gov (United States)

Hirota, A; Taki, S; Kawaii, S; Yano, M; Abe, N

2000-05-01

Guided by their DPPH radical-scavenging activity, nine compounds were isolated from soybean miso. Of these, 8-hydroxydaidzein, 8-hydroxygenistein and syringic acid had as high DPPH radical-scavenging activity as that of alpha-tocopherol. The antiproliferative activity of four of the isolated isoflavones toward three cancer cell lines was examined. 8-Hydroxygenistein showed the highest activity (IC50=5.2 microM) toward human promyelocytic leukemia cells (HL-60).

Effect of New Water-Soluble Dendritic Phthalocyanines on Human Colorectal and Liver Cancer Cell Lines

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Ebru YABAŞ

2017-08-01

Full Text Available Human hepatocellular carcinoma (HepG2 cells and colorectal adenocarcinoma (DLD-1 cells were treated with the synthesized water soluble phthalocyanine derivatives to understand the effect of the compounds both on colorectal and liver cancer cells. The compounds inhibited cell proliferation and displayed cytotoxic effect on these cancer cell lines however; the effect of the compounds on healthy control fibroblast cell line was comparatively lower. The compounds can be employed for cancer treatment as anticancer agents.

Crispoic acid, a new compound from Laelia marginata (Orchidaceae), and biological evaluations against parasites, human cancer cell lines and Zika virus.

Science.gov (United States)

Belloto, Andrezza C; Souza, Gredson K; Perin, Paula C; Schuquel, Ivania T A; Santin, Silvana M O; Chiavelli, Lucas U R; Garcia, Francielle P; Kaplum, Vanessa; Rodrigues, Jean H S; Scariot, Débora B; Delvecchio, Rodrigo; Machado-Ferreira, Erik; Santana Aguiar, Renato; Soares, Carlos A G; Nakamura, Celso V; Pomini, Armando M

2017-11-08

The phytochemical study of Laelia marginata (Lindl.) L. O. Williams (Orchidaceae) led to the isolation of a new natural product named crispoic acid (1), together with six other known compounds (2-7). The new natural product was identified as a dimer of eucomic acid and was structurally characterised based upon 1D and 2D NMR and HRMS data. Biological assays with plant crude extract, fractions and isolated compounds were performed against two human cancer cell lines (Hela and Siha), and the tropical parasites Trypanosoma cruzi and Leishmania (Leishmania) amazonensis. The phenantrenoid 9,10-dihydro-4-methoxyphenanthren-2,7-diol 2 was active against Hela and Siha cells (CC 50 5.86 ± 0.19 and 20.78 ± 2.72 μg/mL, respectively). Sub-lethal concentrations of the flavone rhamnazin 4 were not able to rescue the viability of the Vero cells infected by Zika virus.

EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds.

Science.gov (United States)

Giammarile, Francesco; Bodei, Lisa; Chiesa, Carlo; Flux, Glenn; Forrer, Flavio; Kraeber-Bodere, Françoise; Brans, Boudewijn; Lambert, Bieke; Konijnenberg, Mark; Borson-Chazot, Françoise; Tennvall, Jan; Luster, Markus

2011-07-01

Primary liver cancers (i.e. hepatocellular carcinoma or cholangiocarcinoma) are worldwide some of the most frequent cancers, with rapidly fatal liver failure in a large majority of patients. Curative therapy consists of surgery (i.e. resection or liver transplantation), but only 10-20% of patients are candidates for this. In other patients, a variety of palliative treatments can be given, such as chemoembolization, radiofrequency ablation or recently introduced tyrosine kinase inhibitors, e.g. sorafenib. Colorectal cancer is the second most lethal cancer in Europe and liver metastases are prevalent either at diagnosis or in follow-up. These patients are usually treated by a sequence of surgery, chemotherapy and antibody therapy [Okuda et al. (Cancer 56:918-928, 1985); Schafer and Sorrell (Lancet 353:1253-1257, 1999); Leong et al. (Arnold, London, 1999)]. Radioembolization is an innovative therapeutic approach defined as the injection of micron-sized embolic particles loaded with a radioisotope by use of percutaneous intra-arterial techniques. Advantages of the use of these intra-arterial radioactive compounds are the ability to deliver high doses of radiation to small target volumes, the relatively low toxicity profile, the possibility to treat the whole liver including microscopic disease and the feasibility of combination with other therapy modalities. Disadvantages are mainly due to radioprotection constraints mainly for (131)I-labelled agents, logistics and the possibility of inadvertent delivery or shunting [Novell et al. (Br J Surg 78:901-906, 1991)]. The Therapy, Oncology and Dosimetry Committees have worked together in order to revise the European Association of Nuclear Medicine (EANM) guidelines on the use of the radiopharmaceutical (131)I-Lipiodol (Lipiocis®, IBA, Brussels, Belgium) and include the newer medical devices with (90)Y-microspheres. (90)Y is either bound to resin (SIR-Spheres®, Sirtex Medical, Lane Cove, Australia) or embedded in a glass

Identification of TRAIL-inducing compounds highlights small molecule ONC201/TIC10 as a unique anti-cancer agent that activates the TRAIL pathway.

Science.gov (United States)

Allen, Joshua E; Krigsfeld, Gabriel; Patel, Luv; Mayes, Patrick A; Dicker, David T; Wu, Gen Sheng; El-Deiry, Wafik S

2015-05-01

We previously reported the identification of ONC201/TIC10, a novel small molecule inducer of the human TRAIL gene that improves efficacy-limiting properties of recombinant TRAIL and is in clinical trials in advanced cancers based on its promising safety and antitumor efficacy in several preclinical models. We performed a high throughput luciferase reporter screen using the NCI Diversity Set II to identify TRAIL-inducing compounds. Small molecule-mediated induction of TRAIL reporter activity was relatively modest and the majority of the hit compounds induced low levels of TRAIL upregulation. Among the candidate TRAIL-inducing compounds, TIC9 and ONC201/TIC10 induced sustained TRAIL upregulation and apoptosis in tumor cells in vitro and in vivo. However, ONC201/TIC10 potentiated tumor cell death while sparing normal cells, unlike TIC9, and lacked genotoxicity in normal fibroblasts. Investigating the effects of TRAIL-inducing compounds on cell signaling pathways revealed that TIC9 and ONC201/TIC10, which are the most potent inducers of cell death, exclusively activate Foxo3a through inactivation of Akt/ERK to upregulate TRAIL and its pro-apoptotic death receptor DR5. These studies reveal the selective activity of ONC201/TIC10 that led to its selection as a lead compound for this novel class of antitumor agents and suggest that ONC201/TIC10 is a unique inducer of the TRAIL pathway through its concomitant regulation of the TRAIL ligand and its death receptor DR5.

Utilization of Cyanoacetohydrazide and Oxadiazolyl Acetonitrile in the Synthesis of Some New Cytotoxic Heterocyclic Compounds.

Science.gov (United States)

Shaker, Soheir A; Marzouk, Magda I

2016-01-29

A (pyridazinyl)acetate derivative was reacted with thiosemicarbazide and hydrazine hydrate to yield spiropyridazinone and acetohydrazide derivatives, respectively. The acetohydrazide derivative was used as a starting material for synthesizing some new heterocyclic compounds such as oxoindolinylidene, dimethylpyrazolyl, methylpyrazolyl, oxopyrazolyl, cyanoacetylacetohydrazide and oxadiazolylacetonitrile derivatives. The behavior of the cyanoacetylacetohydrazide and oxadiazolylacetonitrile derivatives towards nitrogen and carbon nucleophiles was investigated. The assigned structures of the prepared compounds were elucidated by spectral methods (IR, ¹H-NMR (13)C-NMR and mass spectroscopy). Some of the newly prepared compounds were tested in vitro against a panel of four human tumor cell lines, namely hepatocellular carcinoma (liver) HePG-2, colon cancer HCT-116, human prostate cancer PC3, and mammary gland breast MCF-7. Also they were tested as antioxidants. Almost all of the tested compounds showed satisfactory activity.

Carcinogenic compounds in alcoholic beverages: an update.

Science.gov (United States)

Pflaum, Tabea; Hausler, Thomas; Baumung, Claudia; Ackermann, Svenja; Kuballa, Thomas; Rehm, Jürgen; Lachenmeier, Dirk W

2016-10-01

The consumption of alcoholic beverages has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) since 1988. More recently, in 2010, ethanol as the major constituent of alcoholic beverages and its metabolite acetaldehyde were also classified as carcinogenic to humans. Alcoholic beverages as multi-component mixtures may additionally contain further known or suspected human carcinogens as constituent or contaminant. This review will discuss the occurrence and toxicology of eighteen carcinogenic compounds (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, glyphosate, lead, 3-MCPD, 4-methylimidazole, N-nitrosodimethylamine, pulegone, ochratoxin A, safrole) occurring in alcoholic beverages as identified based on monograph reviews by the IARC. For most of the compounds of alcoholic beverages, quantitative risk assessment provided evidence for only a very low risk (such as margins of exposure above 10,000). The highest risk was found for ethanol, which may reach exposures in ranges known to increase the cancer risk even at moderate drinking (margin of exposure around 1). Other constituents that could pose a risk to the drinker were inorganic lead, arsenic, acetaldehyde, cadmium and ethyl carbamate, for most of which mitigation by good manufacturing practices is possible. Nevertheless, due to the major effect of ethanol, the cancer burden due to alcohol consumption can only be reduced by reducing alcohol consumption in general or by lowering the alcoholic strength of beverages.

Olive oil compounds inhibit vascular endothelial growth factor receptor-2 phosphorylation

International Nuclear Information System (INIS)

Lamy, Sylvie; Ouanouki, Amira; Béliveau, Richard; Desrosiers, Richard R.

2014-01-01

Vascular endothelial growth factor (VEGF) triggers crucial signaling processes that regulate tumor angiogenesis and, therefore, represents an attractive target for the development of novel anticancer therapeutics. Several epidemiological studies have confirmed that abundant consumption of foods from plant origin is associated with reduced risk of developing cancers. In the Mediterranean basin, the consumption of extra virgin olive oil is an important constituent of the diet. Compared to other vegetable oils, the presence of several phenolic antioxidants in olive oil is believed to prevent the occurrence of a variety of pathological processes, such as cancer. While the strong antioxidant potential of these molecules is well characterized, their antiangiogenic activities remain unknown. The aim of this study is to investigate whether tyrosol (Tyr), hydroxytyrosol (HT), taxifolin (Tax), oleuropein (OL) and oleic acid (OA), five compounds contained in extra virgin olive oil, can affect in vitro angiogenesis. We found that HT, Tax and OA were the most potent angiogenesis inhibitors through their inhibitory effect on specific autophosphorylation sites of VEGFR-2 (Tyr951, Tyr1059, Tyr1175 and Tyr1214) leading to the inhibition of endothelial cell (EC) signaling. Inhibition of VEGFR-2 by these olive oil compounds significantly reduced VEGF-induced EC proliferation and migration as well as their morphogenic differentiation into capillary-like tubular structures in Matrigel. Our study demonstrates that HT, Tax and OA are novel and potent inhibitors of the VEGFR-2 signaling pathway. These findings emphasize the chemopreventive properties of olive oil and highlight the importance of nutrition in cancer prevention. - Highlights: • We investigated five compounds contained in extra virgin olive oil on angiogenesis. • Hydroxytyrosol, taxifolin and oleic acid are the best angiogenesis inhibitors. • Olive oil compounds affect endothelial cell functions essential for

Olive oil compounds inhibit vascular endothelial growth factor receptor-2 phosphorylation

Energy Technology Data Exchange (ETDEWEB)

Lamy, Sylvie, E-mail: lamy.sylvie@uqam.ca; Ouanouki, Amira; Béliveau, Richard; Desrosiers, Richard R.

2014-03-10

Vascular endothelial growth factor (VEGF) triggers crucial signaling processes that regulate tumor angiogenesis and, therefore, represents an attractive target for the development of novel anticancer therapeutics. Several epidemiological studies have confirmed that abundant consumption of foods from plant origin is associated with reduced risk of developing cancers. In the Mediterranean basin, the consumption of extra virgin olive oil is an important constituent of the diet. Compared to other vegetable oils, the presence of several phenolic antioxidants in olive oil is believed to prevent the occurrence of a variety of pathological processes, such as cancer. While the strong antioxidant potential of these molecules is well characterized, their antiangiogenic activities remain unknown. The aim of this study is to investigate whether tyrosol (Tyr), hydroxytyrosol (HT), taxifolin (Tax), oleuropein (OL) and oleic acid (OA), five compounds contained in extra virgin olive oil, can affect in vitro angiogenesis. We found that HT, Tax and OA were the most potent angiogenesis inhibitors through their inhibitory effect on specific autophosphorylation sites of VEGFR-2 (Tyr951, Tyr1059, Tyr1175 and Tyr1214) leading to the inhibition of endothelial cell (EC) signaling. Inhibition of VEGFR-2 by these olive oil compounds significantly reduced VEGF-induced EC proliferation and migration as well as their morphogenic differentiation into capillary-like tubular structures in Matrigel. Our study demonstrates that HT, Tax and OA are novel and potent inhibitors of the VEGFR-2 signaling pathway. These findings emphasize the chemopreventive properties of olive oil and highlight the importance of nutrition in cancer prevention. - Highlights: • We investigated five compounds contained in extra virgin olive oil on angiogenesis. • Hydroxytyrosol, taxifolin and oleic acid are the best angiogenesis inhibitors. • Olive oil compounds affect endothelial cell functions essential for

Boron compounds in neutron capture therapy of tumors

International Nuclear Information System (INIS)

Strouf, O.; Gregor, V.

1986-01-01

In the selective incorporation of a sufficient amount of a compound containing boron isotope 10 B in the tumor tissue for neutron capture therapy, high efficiency is achieved in tumor destruction while sparing the surrounding tissues. In the treatment of brain tumors, 4-carboxy phenylboric acid and the disodium salt of mercaptoundecahydrododecaborate were successfully tested. The use of the compounds minimizes radiation damage to the blood stream of the brain. In case of melanomas the L-DOPA-borate complex, boronophenylalanine and chlorpromazine preparations containing 10 B are used. In the treatment of cancer of the reproductive organs, boron derivatives of estradiol and testosterone have been proven. The immunobiological procedure, i.e., the use of antibodies with bound boron compounds, is being intensively studied. (M.D.)

Impact of nutrition on noncoding RNA epigenetics in breast and gynecological cancer

Directory of Open Access Journals (Sweden)

Rosanna H. E. Krakowsky

2015-05-01

Full Text Available Cancer is the second leading cause of death in females. According to the American Cancer Society, there are 327,660 new cases in breast and gynecological cancers estimated in 2014, placing emphasis on the need for cancer prevention and new cancer treatment strategies. One important approach to cancer prevention involves phytochemicals, biologically active compounds derived from plants. A variety of studies on the impact of dietary compounds found in cruciferous vegetables, green tea and spices like curry and black pepper have revealed epigenetic changes in female cancers. Thus, an important emerging topic comprises epigenetic changes due to the modulation of noncoding RNA levels. Since it has been shown that noncoding RNAs such as microRNAs and long noncoding RNAs are aberrantly expressed in cancer and furthermore are linked to distinct cancer phenotypes, understanding the effects of dietary compounds and supplements on the epigenetic modulator noncoding RNA is of great interest. This article reviews the current findings on nutrition-induced changes in breast and gynecological cancers at the noncoding RNA level.

Six coordination compounds: mode of cytotoxic action and biological evaluation

Directory of Open Access Journals (Sweden)

ali aydin

2016-09-01

Full Text Available This study describes the biological and anticancer properties of followed coordination compounds. IR spectra, magnetic properties, thermal analyses and crystal structures of six cyanido-complexes derivatives with [MII(CN4]2- (MII= Ni and Pd and [Co(CN6]3- anions and N-bishydeten (N,N-bis(2-hydroxyethylethylenediamine as a capping ligand have been previously reported. Here, we investigated these complexes denoted as[Ni(N-bishydetenNi(CN4] (C1, [Zn2(N-bishydeten2Ni(CN4] (C2, [Ni(N-bishydetenPd(CN4] (C3, [Cd(N-bishydeten2][Pd(CN4] (C4, [Ni2(N-bishydeten2Co(CN6].3H2O (C5 and K[Cd(N-bishydetenCo(CN6].1.5H2O (C6, which were tested for their anti-proliferative activity against human cervical cancer (HeLa, human colon cancer (HT29, rat glioma (C6 and African green monkey kidney (Vero cell lines. The DNA/BSA binding affinities of these compounds were also elucidated by spectroscopic titrations, displacement experiments and electrophoresis measurements. Studies on cancerous cells revealed that C1, C2, C4 and C6 exhibited significant antitumor activity and inhibited tumor progression in testing cell lines and showed high solubility in the solvent. Absorbance and emission spectra data results revealed that the complexes interact with the DNA via groove binding mode of interaction. Overall, these compounds have been found to demonstrate effective anti-proliferative activity against the cancer cell lines, indicating that they are a potent candidate for preclinical or clinical study.

Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides

Science.gov (United States)

Birsoy, Kıvanç; Possemato, Richard; Lorbeer, Franziska K.; Bayraktar, Erol C.; Thiru, Prathapan; Yucel, Burcu; Wang, Tim; Chen, Walter W.; Clish, Clary B.; Sabatini, David M.

2014-04-01

As the concentrations of highly consumed nutrients, particularly glucose, are generally lower in tumours than in normal tissues, cancer cells must adapt their metabolism to the tumour microenvironment. A better understanding of these adaptations might reveal cancer cell liabilities that can be exploited for therapeutic benefit. Here we developed a continuous-flow culture apparatus (Nutrostat) for maintaining proliferating cells in low-nutrient media for long periods of time, and used it to undertake competitive proliferation assays on a pooled collection of barcoded cancer cell lines cultured in low-glucose conditions. Sensitivity to low glucose varies amongst cell lines, and an RNA interference (RNAi) screen pinpointed mitochondrial oxidative phosphorylation (OXPHOS) as the major pathway required for optimal proliferation in low glucose. We found that cell lines most sensitive to low glucose are defective in the OXPHOS upregulation that is normally caused by glucose limitation as a result of either mitochondrial DNA (mtDNA) mutations in complex I genes or impaired glucose utilization. These defects predict sensitivity to biguanides, antidiabetic drugs that inhibit OXPHOS, when cancer cells are grown in low glucose or as tumour xenografts. Notably, the biguanide sensitivity of cancer cells with mtDNA mutations was reversed by ectopic expression of yeast NDI1, a ubiquinone oxidoreductase that allows bypass of complex I function. Thus, we conclude that mtDNA mutations and impaired glucose utilization are potential biomarkers for identifying tumours with increased sensitivity to OXPHOS inhibitors.

Acculturation in the adaptation of Chinese-American women to breast cancer: a mixed-method approach.

Science.gov (United States)

Tsai, Tzu-I; Morisky, Donald E; Kagawa-Singer, Marjorie; Ashing-Giwa, Kimlin T

2011-12-01

To explore how and to what extent acculturation and immigration affect Chinese-American immigrant women's breast cancer experience. Acculturation is an important indicator for immigrant health. Less empirical research has been conducted on the association between acculturation and breast cancer experience among Chinese immigrant women in the USA. A mixed methods study. A total of 107 Chinese-American women with breast cancer completed the structured questionnaire survey, and 16 women completed face-to-face in-depth interviews. In the quantitative findings, acculturation was related to health beliefs, social support and life stress. Cultural interpretations of the qualitative information are offered to show that breast cancer experience was intertwined with cultural adaptation in a given immigrant environment. Chinese cultural beliefs persistently, even after years of immigration, guide Chinese-American immigrant women to respond to breast cancer across the meaning of health and illness, family ties and involvement and social interaction. Our findings show that acculturation is related to health beliefs, social support and life stress in the trajectory of breast cancer adaptation among Chinese-American immigrant women. Life stresses derived from immigration bring additional difficulties for immigrant women living with cancer. This study pinpoints that traditional cultural beliefs and immigration stress may influence Chinese-American women to cope with breast cancer. To promote culturally sensitive cancer care for immigrants, healthcare professionals should be aware of and learn intercultural competence. Ethnic social support or outreach healthcare programme may benefit new immigrant families or the immigrant families, who lack social connection, to cope with cancer. © 2011 Blackwell Publishing Ltd.

N-Nitroso compounds: Assessing agreement between food frequency questionnaires and 7-day food records

Science.gov (United States)

N-nitroso compounds are recognized as important dietary carcinogens. Accurate assessment of N-nitroso intake is fundamental to advancing research regarding its role with cancer. Previous studies have not used a quantitative database to estimate the intake of these compounds in a US population. To ad...

Deconvoluting complex tissues for expression quantitative trait locus-based analyses

DEFF Research Database (Denmark)

Seo, Ji-Heui; Li, Qiyuan; Fatima, Aquila

2013-01-01

Breast cancer genome-wide association studies have pinpointed dozens of variants associated with breast cancer pathogenesis. The majority of risk variants, however, are located outside of known protein-coding regions. Therefore, identifying which genes the risk variants are acting through present...

Plant-associated bacterial degradation of toxic organic compounds in soil.

LENUS (Irish Health Repository)

McGuinness, Martina

2009-08-01

A number of toxic synthetic organic compounds can contaminate environmental soil through either local (e.g., industrial) or diffuse (e.g., agricultural) contamination. Increased levels of these toxic organic compounds in the environment have been associated with human health risks including cancer. Plant-associated bacteria, such as endophytic bacteria (non-pathogenic bacteria that occur naturally in plants) and rhizospheric bacteria (bacteria that live on and near the roots of plants), have been shown to contribute to biodegradation of toxic organic compounds in contaminated soil and could have potential for improving phytoremediation. Endophytic and rhizospheric bacterial degradation of toxic organic compounds (either naturally occurring or genetically enhanced) in contaminated soil in the environment could have positive implications for human health worldwide and is the subject of this review.

Suppressive Effects of Tea Catechins on Breast Cancer

Science.gov (United States)

Xiang, Li-Ping; Wang, Ao; Ye, Jian-Hui; Zheng, Xin-Qiang; Polito, Curt Anthony; Lu, Jian-Liang; Li, Qing-Sheng; Liang, Yue-Rong

2016-01-01

Tea leaf (Camellia sinensis) is rich in catechins, which endow tea with various health benefits. There are more than ten catechin compounds in tea, among which epigallocatechingallate (EGCG) is the most abundant. Epidemiological studies on the association between tea consumption and the risk of breast cancer were summarized, and the inhibitory effects of tea catechins on breast cancer, with EGCG as a representative compound, were reviewed in the present paper. The controversial results regarding the role of tea in breast cancer and areas for further study were discussed. PMID:27483305

Chemistry and Functionality of Bioactive Compounds Present in Persimmon

Directory of Open Access Journals (Sweden)

Shazia Yaqub

2016-01-01

Full Text Available Extensive research has related the consumption of persimmon with the reduced risk of various diseases and particularly highlighted the presence of bioactive phenolic compounds for their therapeutic properties. Major phenolic compounds present in persimmon are ferulic acid, p-coumaric acid, and gallic acid. β-Cryptoxanthin, lycopene, β-carotene, zeaxanthin, and lutein are important carotenoids having antioxidant potential. They are important to prevent oxidation of low-density lipoproteins, safeguard beta cells of the pancreas, and reduce cardiovascular diseases, cancer, diabetes mellitus, and damage caused by chronic alcohol consumption. In this paper, the chemistry and health benefits of bioactive compounds present in persimmon are reviewed to encourage impending applications and to facilitate further research activities.

Lab-on-a-Drone: Toward Pinpoint Deployment of Smartphone-Enabled Nucleic Acid-Based Diagnostics for Mobile Health Care.

Science.gov (United States)

Priye, Aashish; Wong, Season; Bi, Yuanpeng; Carpio, Miguel; Chang, Jamison; Coen, Mauricio; Cope, Danielle; Harris, Jacob; Johnson, James; Keller, Alexandra; Lim, Richard; Lu, Stanley; Millard, Alex; Pangelinan, Adriano; Patel, Neal; Smith, Luke; Chan, Kamfai; Ugaz, Victor M

2016-05-03

We introduce a portable biochemical analysis platform for rapid field deployment of nucleic acid-based diagnostics using consumer-class quadcopter drones. This approach exploits the ability to isothermally perform the polymerase chain reaction (PCR) with a single heater, enabling the system to be operated using standard 5 V USB sources that power mobile devices (via battery, solar, or hand crank action). Time-resolved fluorescence detection and quantification is achieved using a smartphone camera and integrated image analysis app. Standard sample preparation is enabled by leveraging the drone's motors as centrifuges via 3D printed snap-on attachments. These advancements make it possible to build a complete DNA/RNA analysis system at a cost of ∼$50 ($US). Our instrument is rugged and versatile, enabling pinpoint deployment of sophisticated diagnostics to distributed field sites. This capability is demonstrated by successful in-flight replication of Staphylococcus aureus and λ-phage DNA targets in under 20 min. The ability to perform rapid in-flight assays with smartphone connectivity eliminates delays between sample collection and analysis so that test results can be delivered in minutes, suggesting new possibilities for drone-based systems to function in broader and more sophisticated roles beyond cargo transport and imaging.

Exploring Marine Cyanobacteria for Lead Compounds of Pharmaceutical Importance

Directory of Open Access Journals (Sweden)

Bushra Uzair

2012-01-01

Full Text Available The Ocean, which is called the “mother of origin of life,” is also the source of structurally unique natural products that are mainly accumulated in living organisms. Cyanobacteria are photosynthetic prokaryotes used as food by humans. They are excellent source of vitamins and proteins vital for life. Several of these compounds show pharmacological activities and are helpful for the invention and discovery of bioactive compounds, primarily for deadly diseases like cancer, acquired immunodeficiency syndrome (AIDS, arthritis, and so forth, while other compounds have been developed as analgesics or to treat inflammation, and so forth. They produce a large variety of bioactive compounds, including substances with anticancer and antiviral activity, UV protectants, specific inhibitors of enzymes, and potent hepatotoxins and neurotoxins. Many cyanobacteria produce compounds with potent biological activities. This paper aims to showcase the structural diversity of marine cyanobacterial secondary metabolites with a comprehensive coverage of alkaloids and other applications of cyanobacteria.

Curcumin and Other Polyphenolic Compounds in Head and Neck Cancer Chemoprevention

Directory of Open Access Journals (Sweden)

Philipp Baumeister

2012-01-01

Full Text Available Despite clear results of observational studies linking a diet rich in fruits and vegetables to a decreased cancer risk, large interventional trials evaluating the impact of dietary micronutrient supplementation, mostly vitamins, could not show any beneficial effects. Today it has become clear that a single micronutrient, given in supernutritional doses, cannot match cancer preventive effects of whole fruits and vegetables. In this regard polyphenols came into focus, not only because of their antioxidant potential but also because of their ability to interact with molecular targets within the cells. Because polyphenols occur in many foods and beverages in high concentration and evidence for their anticancer activity is best for tissues they can come into direct contact with, field cancerization predestines upper aerodigestive tract epithelium for cancer chemoprevention by polyphenols. In this paper, we summarize cancer chemopreventive attempts with emphasis on head and neck carcinogenesis and discuss some methodological issues. We present data regarding antimutagenic effects of curcumin and epigallocatechin-3-gallate in human oropharyngeal mucosa cultures exposed to cigarette smoke condensate.

Study on the interaction of chemopreventive compounds and food born carcinogens with cytochrome P450 enzymes

OpenAIRE

Brabencová, Eliška

2013-01-01

The use of food supplements containing natural chemopreventive compounds increased in recent years. Some of the most popular chemopreventive compounds are flavonoids. Due to their natural origin, flavonoids are generally accepted as safe compounds. They exert antioxidant, anti-cancer and anti-inflammatory properties. However, flavonoids should be considered as foreign compounds (xenobiotics). Flavonoids interact with many enzymes, among the most important belong cytochromes P450 (CYPs), key e...

Cure of malignant melanoma by single thermal neutron capture treatment using melanoma-seeking compounds

International Nuclear Information System (INIS)

Mishima, Yutaka; Ichihashi, Masamitsu; Nakanishi, Takafumi

1985-01-01

Since not only malignant melanomas but also many kinds of human cancers, for example thyroid cancer and squamous cell carcinoma, synthesize their specific protein, much attention has been paid to the establishment of selective thermal neutron capture treatment of malignant melanoma as a prototype of such cancer cells. This paper presents 10 B chlorpromazine compounds and 10 B 1 -para-boronophenylalanine ( 10 B 1 -BPA) as tumor-seeking 10 B compounds which themselves possess selective affinity for the specific metabolic activity of the target cancer cells. An overview of the following studies on the effects of 10 B 1 -BPA in the thermal neutron capture treatment of melanoma is provided: 1) in vitro studies on specific enhanced melanoma cell killing effects of 10 B 1 -BPA; 2) in vivo studies on therapeutic effects of 10 B 1 -BPA using melanoma-bearing hamsters; and 3) preclinical therapeutic experiments using spontaneously occurring malignant melanoma in Duroc pig skin, including experiments in which melanoma was successfully cured. (Namekawa, K.)

Rhus verniciflua Stokes against Advanced Cancer: A Perspective from the Korean Integrative Cancer Center

Directory of Open Access Journals (Sweden)

Woncheol Choi

2012-01-01

Full Text Available Active anticancer molecules have been searched from natural products; many drugs were developed from either natural products or their derivatives following the conventional pharmaceutical paradigm of drug discovery. However, the advances in the knowledge of cancer biology have led to personalized medicine using molecular-targeted agents which create new paradigm. Clinical benefit is dependent on individual biomarker and overall survival is prolonged through cytostatic rather than cytotoxic effects to cancer cell. Therefore, a different approach is needed from the single lead compound screening model based on cytotoxicity. In our experience, the Rhus verniciflua stoke (RVS extract traditionally used for cancer treatment is beneficial to some advanced cancer patients though it is herbal extract not single compound, and low cytotoxic in vitro. The standardized RVS extract's action mechanisms as well as clinical outcomes are reviewed here. We hope that these preliminary results would stimulate different investigation in natural products from conventional chemicals.

Approaches that ascertain the role of dietary compounds in colonic cancer cells

NARCIS (Netherlands)

Bordonaro, M.; Venema, K.; Putri, A.K.; Lazarova, D.

2014-01-01

Preventive approaches against cancer have not been fully developed and applied. For example, the incidence of some types of cancer, including colon cancer, is highly dependent upon lifestyle, and therefore, amenable to prevention. Among the lifestyle factors, diet strongly affects the incidence of

A 3D correction method for predicting the readings of a PinPoint chamber on the CyberKnife® M6™ machine

Science.gov (United States)

Zhang, Yongqian; Brandner, Edward; Ozhasoglu, Cihat; Lalonde, Ron; Heron, Dwight E.; Saiful Huq, M.

2018-02-01

The use of small fields in radiation therapy techniques has increased substantially in particular in stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT). However, as field size reduces further still, the response of the detector changes more rapidly with field size, and the effects of measurement uncertainties become increasingly significant due to the lack of lateral charged particle equilibrium, spectral changes as a function of field size, detector choice, and subsequent perturbations of the charged particle fluence. This work presents a novel 3D dose volume-to-point correction method to predict the readings of a 0.015 cc PinPoint chamber (PTW 31014) for both small static-fields and composite-field dosimetry formed by fixed cones on the CyberKnife® M6™ machine. A 3D correction matrix is introduced to link the 3D dose distribution to the response of the PinPoint chamber in water. The parameters of the correction matrix are determined by modeling its 3D dose response in circular fields created using the 12 fixed cones (5 mm-60 mm) on a CyberKnife® M6™ machine. A penalized least-square optimization problem is defined by fitting the calculated detector reading to the experimental measurement data to generate the optimal correction matrix; the simulated annealing algorithm is used to solve the inverse optimization problem. All the experimental measurements are acquired for every 2 mm chamber shift in the horizontal planes for each field size. The 3D dose distributions for the measurements are calculated using the Monte Carlo calculation with the MultiPlan® treatment planning system (Accuray Inc., Sunnyvale, CA, USA). The performance evaluation of the 3D conversion matrix is carried out by comparing the predictions of the output factors (OFs), off-axis ratios (OARs) and percentage depth dose (PDD) data to the experimental measurement data. The discrepancy of the measurement and the prediction data for composite fields is also

REVIEW PAPER-MARINE MICROBIAL BIOACTIVE COMPOUNDS

OpenAIRE

Kalyani. P*, Hemalatha. K. P. J

2016-01-01

Oceans have borne most of the biological activities on our planet. A number of biologically active compounds with varying degrees of action, such as anti-tumor, anti-cancer, anti-microtubule, anti-proliferative, cytotoxic, photo protective, as well as antibiotic and antifouling properties, have been isolated to date from marine sources. The marine environment also represents a largely unexplored source for isolation of new microbes (bacteria, fungi, actinomycetes, microalgae-cyanobacteria and...

Cytotoxic and Antimicrobial Compounds from the Marine-Derived Fungus, Penicillium Species

Directory of Open Access Journals (Sweden)

Diaa T. A. Youssef

2018-02-01

Full Text Available The organic extract of liquid cultures of the marine-derived Penicillium sp. was investigated. Fractionation of the extracts of the fungus led to the purification and identification of two new compounds, penicillatides A (1 and B (2, together with the previously reported cyclo(R-Pro–S-Phe (3 and cyclo(R-Pro–R-Phe (4. The structures of compounds 1–4 were assigned by extensive interpretation of their NMR and high-resolution mass spectrometry (HRMS. The antiproliferative and cytotoxic activities of the compounds against three human cancer cell lines as well as their antimicrobial activity against several pathogens were evaluated. Compounds 2–4 displayed variable cytotoxic and antimicrobial activities.

Pinpointing particles

Energy Technology Data Exchange (ETDEWEB)

Miller, David J.

1987-10-15

The Conference on Position-Sensitive Detectors held at London's University College from 7-11 September highlighted the importance and the growing applications of these precision devices in many branches of science, underlining once again the high spinoff potential for techniques developed inside particle physics.

Pinpointing particles

International Nuclear Information System (INIS)

Miller, David J.

1987-01-01

The Conference on Position-Sensitive Detectors held at London's University College from 7-11 September highlighted the importance and the growing applications of these precision devices in many branches of science, underlining once again the high spinoff potential for techniques developed inside particle physics

Nanoencapsulation of pomegranate bioactive compounds for breast cancer chemoprevention.

Science.gov (United States)

Shirode, Amit B; Bharali, Dhruba J; Nallanthighal, Sameera; Coon, Justin K; Mousa, Shaker A; Reliene, Ramune

2015-01-01

Pomegranate polyphenols are potent antioxidants and chemopreventive agents but have low bioavailability and a short half-life. For example, punicalagin (PU), the major polyphenol in pomegranates, is not absorbed in its intact form but is hydrolyzed to ellagic acid (EA) moieties and rapidly metabolized into short-lived metabolites of EA. We hypothesized that encapsulation of pomegranate polyphenols into biodegradable sustained release nanoparticles (NPs) may circumvent these limitations. We describe here the development, characterization, and bioactivity assessment of novel formulations of poly(D,L-lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) NPs loaded with pomegranate extract (PE) or individual polyphenols such as PU or EA. Monodispersed, spherical 150-200 nm average diameter NPs were prepared by the double emulsion-solvent evaporation method. Uptake of Alexa Fluor-488-labeled NPs was evaluated in MCF-7 breast cancer cells over a 24-hour time course. Confocal fluorescent microscopy revealed that PLGA-PEG NPs were efficiently taken up, and the uptake reached the maximum at 24 hours. In addition, we examined the antiproliferative effects of PE-, PU-, and/or EA-loaded NPs in MCF-7 and Hs578T breast cancer cells. We found that PE, PU, and EA nanoprototypes had a 2- to 12-fold enhanced effect on cell growth inhibition compared to their free counterparts, while void NPs did not affect cell growth. PU-NPs were the most potent nanoprototype of pomegranates. Thus, PU may be the polyphenol of choice for further chemoprevention studies with pomegranate nanoprototypes. These data demonstrate that nanotechnology-enabled delivery of pomegranate polyphenols enhances their anticancer effects in breast cancer cells. Thus, pomegranate polyphenols are promising agents for nanochemoprevention of breast cancer.

Identification of new candidate drugs for lung cancer using chemical-chemical interactions, chemical-protein interactions and a K-means clustering algorithm.

Science.gov (United States)

Lu, Jing; Chen, Lei; Yin, Jun; Huang, Tao; Bi, Yi; Kong, Xiangyin; Zheng, Mingyue; Cai, Yu-Dong

2016-01-01

Lung cancer, characterized by uncontrolled cell growth in the lung tissue, is the leading cause of global cancer deaths. Until now, effective treatment of this disease is limited. Many synthetic compounds have emerged with the advancement of combinatorial chemistry. Identification of effective lung cancer candidate drug compounds among them is a great challenge. Thus, it is necessary to build effective computational methods that can assist us in selecting for potential lung cancer drug compounds. In this study, a computational method was proposed to tackle this problem. The chemical-chemical interactions and chemical-protein interactions were utilized to select candidate drug compounds that have close associations with approved lung cancer drugs and lung cancer-related genes. A permutation test and K-means clustering algorithm were employed to exclude candidate drugs with low possibilities to treat lung cancer. The final analysis suggests that the remaining drug compounds have potential anti-lung cancer activities and most of them have structural dissimilarity with approved drugs for lung cancer.

High-throughput molecular analysis in lung cancer: insights into biology and potential clinical applications.

Science.gov (United States)

Ocak, S; Sos, M L; Thomas, R K; Massion, P P

2009-08-01

During the last decade, high-throughput technologies including genomic, epigenomic, transcriptomic and proteomic have been applied to further our understanding of the molecular pathogenesis of this heterogeneous disease, and to develop strategies that aim to improve the management of patients with lung cancer. Ultimately, these approaches should lead to sensitive, specific and noninvasive methods for early diagnosis, and facilitate the prediction of response to therapy and outcome, as well as the identification of potential novel therapeutic targets. Genomic studies were the first to move this field forward by providing novel insights into the molecular biology of lung cancer and by generating candidate biomarkers of disease progression. Lung carcinogenesis is driven by genetic and epigenetic alterations that cause aberrant gene function; however, the challenge remains to pinpoint the key regulatory control mechanisms and to distinguish driver from passenger alterations that may have a small but additive effect on cancer development. Epigenetic regulation by DNA methylation and histone modifications modulate chromatin structure and, in turn, either activate or silence gene expression. Proteomic approaches critically complement these molecular studies, as the phenotype of a cancer cell is determined by proteins and cannot be predicted by genomics or transcriptomics alone. The present article focuses on the technological platforms available and some proposed clinical applications. We illustrate herein how the "-omics" have revolutionised our approach to lung cancer biology and hold promise for personalised management of lung cancer.

Organotypic Culture of Breast Tumor Explants as a Multicellular System for the Screening of Natural Compounds with Antineoplastic Potential

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Irma Edith Carranza-Torres

2015-01-01

Full Text Available Breast cancer is the leading cause of death in women worldwide. The search for novel compounds with antitumor activity, with less adverse effects and higher efficacy, and the development of methods to evaluate their toxicity is an area of ​​intense research. In this study we implemented the preparation and culture of breast tumor explants, which were obtained from precision-cut breast tumor slices. In order to validate the model we are proposing to screen antineoplastic effect of natural compounds, we selected caffeic acid, ursolic acid, and rosmarinic acid. Using the Krumdieck tissue slicer, precision-cut tissue slices were prepared from breast cancer samples; from these slices, 4 mm explants were obtained and incubated with the selected compounds. Viability was assessed by Alamar Blue assay, LDH release, and histopathological criteria. Results showed that the viability of the explants cultured in the presence of paclitaxel (positive control decreased significantly (P<0.05; however, tumor samples responded differently to each compound. When the explants were coincubated with paclitaxel and compounds, a synergic effect was observed. This study shows that ex vivo culture of breast cancer explants offers a suitable alternative model for evaluating natural or synthetic compounds with antitumor properties within the complex microenvironment of the tumor.

Cancer and non-cancer health effects from food contaminant exposures for children and adults in California: a risk assessment

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Vogt Rainbow

2012-11-01

Full Text Available Abstract Background In the absence of current cumulative dietary exposure assessments, this analysis was conducted to estimate exposure to multiple dietary contaminants for children, who are more vulnerable to toxic exposure than adults. Methods We estimated exposure to multiple food contaminants based on dietary data from preschool-age children (2–4 years, n=207, school-age children (5–7 years, n=157, parents of young children (n=446, and older adults (n=149. We compared exposure estimates for eleven toxic compounds (acrylamide, arsenic, lead, mercury, chlorpyrifos, permethrin, endosulfan, dieldrin, chlordane, DDE, and dioxin based on self-reported food frequency data by age group. To determine if cancer and non-cancer benchmark levels were exceeded, chemical levels in food were derived from publicly available databases including the Total Diet Study. Results Cancer benchmark levels were exceeded by all children (100% for arsenic, dieldrin, DDE, and dioxins. Non-cancer benchmarks were exceeded by >95% of preschool-age children for acrylamide and by 10% of preschool-age children for mercury. Preschool-age children had significantly higher estimated intakes of 6 of 11 compounds compared to school-age children (p Conclusions Dietary strategies to reduce exposure to toxic compounds for which cancer and non-cancer benchmarks are exceeded by children vary by compound. These strategies include consuming organically produced dairy and selected fruits and vegetables to reduce pesticide intake, consuming less animal foods (meat, dairy, and fish to reduce intake of persistent organic pollutants and metals, and consuming lower quantities of chips, cereal, crackers, and other processed carbohydrate foods to reduce acrylamide intake.

A review of phenolic compounds in oil-bearing plants: Distribution, identification and occurrence of phenolic compounds.

Science.gov (United States)

Alu'datt, Muhammad H; Rababah, Taha; Alhamad, Mohammad N; Al-Mahasneh, Majdi A; Almajwal, Ali; Gammoh, Sana; Ereifej, Khalil; Johargy, Ayman; Alli, Inteaz

2017-03-01

Over the last two decades, separation, identification and measurement of the total and individual content of phenolic compounds has been widely investigated. Recently, the presence of a wide range of phenolic compounds in oil-bearing plants has been shown to contribute to their therapeutic properties, including anti-cancer, anti-viral, anti-oxidant, hypoglycemic, hypo-lipidemic, and anti-inflammatory activities. Phenolics in oil-bearing plants are now recognized as important minor food components due to several organoleptic and health properties, and they are used as food or sources of food ingredients. Variations in the content of phenolics in oil-bearing plants have largely been attributed to several factors, including the cultivation, time of harvest and soil types. A number of authors have suggested that the presence phenolics in extracted proteins, carbohydrates and oils may contribute to objectionable off flavors The objective of this study was to review the distribution, identification and occurrence of free and bound phenolic compounds in oil-bearing plants. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bioactive Compounds and Antioxidant Activity in Different Types of Berries

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Sona Skrovankova

2015-10-01

Full Text Available Berries, especially members of several families, such as Rosaceae (strawberry, raspberry, blackberry, and Ericaceae (blueberry, cranberry, belong to the best dietary sources of bioactive compounds (BAC. They have delicious taste and flavor, have economic importance, and because of the antioxidant properties of BAC, they are of great interest also for nutritionists and food technologists due to the opportunity to use BAC as functional foods ingredients. The bioactive compounds in berries contain mainly phenolic compounds (phenolic acids, flavonoids, such as anthocyanins and flavonols, and tannins and ascorbic acid. These compounds, either individually or combined, are responsible for various health benefits of berries, such as prevention of inflammation disorders, cardiovascular diseases, or protective effects to lower the risk of various cancers. In this review bioactive compounds of commonly consumed berries are described, as well as the factors influencing their antioxidant capacity and their health benefits.

Non-canonical programmed cell death mechanisms triggered by natural compounds.

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Diederich, Marc; Cerella, Claudia

2016-10-01

Natural compounds are the fundament of pharmacological treatments and more than 50% of all anticancer drugs are of natural origins or at least derived from scaffolds present in Nature. Over the last 25 years, molecular mechanisms triggered by natural anticancer compounds were investigated. Emerging research showed that molecules of natural origins are useful for both preventive and therapeutic purposes by targeting essential hallmarks and enabling characteristics described by Hanahan and Weinberg. Moreover, natural compounds were able to change the differentiation status of selected cell types. One of the earliest response of cells treated by pharmacologically active compounds is the change of its morphology leading to ultra-structural perturbations: changes in membrane composition, cytoskeleton integrity, alterations of the endoplasmic reticulum, mitochondria and of the nucleus lead to formation of morphological alterations that are a characteristic of both compound and cancer type preceding cell death. Apoptosis and autophagy were traditionally considered as the most prominent cell death or cell death-related mechanisms. By now multiple other cell death modalities were described and most likely involved in response to chemotherapeutic treatment. It can be hypothesized that especially necrosis-related phenotypes triggered by various treatments or evolving from apoptotic or autophagic mechanisms, provide a more efficient therapeutic outcome depending on cancer type and genetic phenotype of the patient. In fact, the recent discovery of multiple regulated forms of necrosis and the initial elucidation of the corresponding cell signaling pathways appear nowadays as important tools to clarify the immunogenic potential of non-canonical forms of cell death induction. Copyright © 2016 Elsevier Ltd. All rights reserved.

Medical Applications and Toxicities of Gallium Compounds

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Christopher R. Chitambar

2010-05-01

Full Text Available Over the past two to three decades, gallium compounds have gained importance in the fields of medicine and electronics. In clinical medicine, radioactive gallium and stable gallium nitrate are used as diagnostic and therapeutic agents in cancer and disorders of calcium and bone metabolism. In addition, gallium compounds have displayed anti-inflammatory and immunosuppressive activity in animal models of human disease while more recent studies have shown that gallium compounds may function as antimicrobial agents against certain pathogens. In a totally different realm, the chemical properties of gallium arsenide have led to its use in the semiconductor industry. Gallium compounds, whether used medically or in the electronics field, have toxicities. Patients receiving gallium nitrate for the treatment of various diseases may benefit from such therapy, but knowledge of the therapeutic index of this drug is necessary to avoid clinical toxicities. Animals exposed to gallium arsenide display toxicities in certain organ systems suggesting that environmental risks may exist for individuals exposed to this compound in the workplace. Although the arsenic moiety of gallium arsenide appears to be mainly responsible for its pulmonary toxicity, gallium may contribute to some of the detrimental effects in other organs. The use of older and newer gallium compounds in clinical medicine may be advanced by a better understanding of their mechanisms of action, drug resistance, pharmacology, and side-effects. This review will discuss the medical applications of gallium and its mechanisms of action, the newer gallium compounds and future directions for development, and the toxicities of gallium compounds in current use.

Carcinogenicity assessment of water-soluble nickel compounds.

Science.gov (United States)

Goodman, Julie E; Prueitt, Robyn L; Dodge, David G; Thakali, Sagar

2009-01-01

IARC is reassessing the human carcinogenicity of nickel compounds in 2009. To address the inconsistencies among results from studies of water-soluble nickel compounds, we conducted a weight-of-evidence analysis of the relevant epidemiological, toxicological, and carcinogenic mode-of-action data. We found the epidemiological evidence to be limited, in that some, but not all, data suggest that exposure to soluble nickel compounds leads to increased cancer risk in the presence of certain forms of insoluble nickel. Although there is no evidence that soluble nickel acts as a complete carcinogen in animals, there is limited evidence that suggests it may act as a tumor promoter. The mode-of-action data suggest that soluble nickel compounds will not be able to cause genotoxic effects in vivo because they cannot deliver sufficient nickel ions to nuclear sites of target cells. Although the mode-of-action data suggest several possible non-genotoxic effects of the nickel ion, it is unclear whether soluble nickel compounds can elicit these effects in vivo or whether these effects, if elicited, would result in tumor promotion. The mode-of-action data equally support soluble nickel as a promoter or as not being a causal factor in carcinogenesis at all. The weight of evidence does not indicate that soluble nickel compounds are complete carcinogens, and there is only limited evidence that they could act as tumor promoters.

Phyto-oestrogens and breast cancer chemoprevention

International Nuclear Information System (INIS)

Limer, Jane L; Speirs, Valerie

2004-01-01

Phytoestrogens are polyphenol compounds of plant origin that exhibit a structural similarity to the mammalian steroid hormone 17β-oestradiol. In Asian nations the staple consumption of phyto-oestrogen-rich foodstuffs correlates with a reduced incidence of breast cancer. Human dietary intervention trials have noted a direct relationship between phyto-oestrogen ingestion and a favourable hormonal profile associated with decreased breast cancer risk. However, these studies failed to ascertain the precise effect of dietary phyto-oestrogens on the proliferation of mammary tissue. Epidemiological and rodent studies crucially suggest that breast cancer chemoprevention by dietary phyto-oestrogen compounds is dependent on ingestion before puberty, when the mammary gland is relatively immature. Phyto-oestrogen supplements are commercially marketed for use by postmenopausal women as natural and safe alternatives to hormone replacement therapy. Of current concern is the effect of phyto-oestrogen compounds on the growth of pre-existing breast tumours. Data are contradictory, with cell culture studies reporting both the oestrogenic stimulation of oestrogen receptor-positive breast cancer cell lines and the antagonism of tamoxifen activity at physiological phyto-oestrogen concentrations. Conversely, phyto-oestrogen ingestion by rodents is associated with the development of less aggressive breast tumours with reduced metastatic potential. Despite the present ambiguity, current data do suggest a potential benefit from use of phyto-oestrogens in breast cancer chemoprevention and therapy. These aspects are discussed

Promising new developments in cancer chemotherapy.

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Ferrante, K; Winograd, B; Canetta, R

1999-01-01

The positive impact on survival of traditional chemotherapeutic agents has renewed interest in developing newer cytotoxic agents and orally active compounds with improved therapeutic indices. In addition, new insights into the pathways of human tumorigenesis have led to novel approaches aimed at specific mechanism-based targets. The taxane class, of which paclitaxel was the first member, has the unique ability to promote and stabilize microtubule function directly, thereby inhibiting mitotic progression and inducing apoptotic cell death. Paclitaxel provides treatment benefit in a broad range of solid tumors including breast, ovarian, and lung cancer. The success with paclitaxel stimulated interest in the microtubule as a new therapeutic target. Taxane analogues with improved preclinical efficacy have been identified and are entering clinical trials. The enthusiasm for oral anticancer agents and the therapeutic importance of platinum compounds has led to the development of JM216 (satraplatin), a novel platinum IV coordination complex with oral activity in cisplatin-resistant cell lines, which is now in phase III trials in prostate cancer. Another compound in late development is DPPE, a chemopotentiator that enhances the in vivo antitumor effects of cytotoxic agents such as doxorubicin, cyclophosphamide, and cisplatin. Agents that inhibit topoisomerase I and II have also been of interest. TAS-103 is a dual topoisomerase I and II inhibitor with preclinical efficacy in a broad spectrum of tumors and in multidrug-resistant tumor cell lines. Vaccination strategies represent a rational therapeutic approach in the minimal residual disease or high-risk adjuvant therapy setting. The GMK and MGV vaccines utilizing ganglioside antigens overexpressed on human tumors such as melanoma and small cell lung cancer appear to induce antibody production reliably at tolerable doses and are under further clinical investigation. Inhibition of matrix metalloproteinases (MMPs) is another

Cancer Cell Cytotoxicities of 1-(4-Substitutedbenzoyl-4-(4-chlorobenzhydrylpiperazine Derivatives

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Mine Yarim

2012-06-01

Full Text Available A series of novel 1-(4-substitutedbenzoyl-4-(4-chlorobenzhydrylpiperazine derivatives 5a–g was designed by a nucleophilic substitution reaction of 1-(4-chlorobenzhydrylpiperazine with various benzoyl chlorides and characterized by elemental analyses, IR and ¹H nuclear magnetic resonance spectra. Cytotoxicity of the compounds was demonstrated on cancer cell lines from liver (HUH7, FOCUS, MAHLAVU, HEPG2, HEP3B, breast (MCF7, BT20, T47D, CAMA-1, colon (HCT-116, gastric (KATO-3 and endometrial (MFE-296 cancer cell lines. Time-dependent cytotoxicity analysis of compound 5a indicated the long-term in situ stability of this compound. All compounds showed significant cell growth inhibitory activity on the selected cancer cell lines.

Screening Some Plants for their Antiproliferative Compounds

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Ufuk Kolak

2012-03-01

Full Text Available This paper covers the screening of the secondary plant products to find a cure against cancer which were piled up during the years. In early stages of these studies highly active antitumor glycoproteins were obtained from native Arizona (USA plants. Later smaller molecules were isolated showing antitumor activity in different test systems. Among these compounds sesquiterpene lactones with an exo-methylene group in the lactone ring, unsaturated diterpenoids and some triterpenoids exhibited activity in vivo and in vitro test systems. A few Colchicum alkaloids showed high activity against murine lymphocytic leukemia (P388. Activity also established in some flavonoidal compounds. Today all around the world research on Natural Products is still going on.

Iron and Reactive Oxygen Species: Friends or Foes of Cancer Cells?

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Bystrom, Laura M.

2014-01-01

Abstract Significance: In this review, the dual nature of both iron and reactive oxygen species (ROS) will be explored in normal and cancer cell metabolism. Although iron and ROS play important roles in cellular homeostasis, they may also contribute to carcinogenesis. On the other hand, many studies have indicated that abrogation of iron metabolism, elevation of ROS, or modification of redox regulatory mechanisms in cancer cells, should be considered as therapeutic approaches for cancer. Recent Advances: Drugs that target different aspects of iron metabolism may be promising therapeutics for cancer. The ability of iron chelators to cause iron depletion and/or elevate ROS levels indicates that these types of compounds have more potential as antitumor medicines than originally expected. Other natural and synthetic compounds that target pathways involved in ROS homeostasis also have potential value alone or in combination with current chemotherapeutics. Critical Issues: Although ROS induction and iron depletion may be targets for cancer therapies, the optimal therapeutic strategies have yet to be identified. This review highlights some of the research that strives to identify such therapeutics. Future Directions: More studies are needed to better understand the role of iron and ROS in carcinogenesis not only as cancer promoters, but also as cytotoxic agents to cancer cells and cancer stem cells (CSCs). Moreover, the structure–activity effects of iron chelators and other compounds that increase ROS and/or disrupt iron metabolism need to be further evaluated to assess the effectiveness and selectivity of these compounds against both cancer and CSCs. Antioxid. Redox Signal. 20, 1917–1924. PMID:23198911

One-year study of polycyclic aromatic compounds at an urban site in Grenoble (France): Seasonal variations, gas/particle partitioning and cancer risk estimation

Energy Technology Data Exchange (ETDEWEB)

Tomaz, Sophie [Institut National de l' Environnement industriel et des RISques (INERIS), Parc Technologique Alata BP2, 60550 Verneuil en Halatte (France); CNRS, EPOC, UMR 5805, F-33405 Talence Cedex (France); Université de Bordeaux, EPOC, UMR 5805, F-33405, Talence Cedex (France); Shahpoury, Pourya [Max Planck Institute for Chemistry, Multiphase Chemistry Department, Mainz (Germany); Jaffrezo, Jean-Luc [Laboratoire de Glaciologie et Géophysiques de l' Environnement (LGGE), Université de Grenoble-Alpes/CNRS, Grenoble (France); Lammel, Gerhard [Max Planck Institute for Chemistry, Multiphase Chemistry Department, Mainz (Germany); Masaryk University, Research Centre for Toxic Compounds in the Environment, Brno (Czech Republic); Perraudin, Emilie; Villenave, Eric [CNRS, EPOC, UMR 5805, F-33405 Talence Cedex (France); Université de Bordeaux, EPOC, UMR 5805, F-33405, Talence Cedex (France); Albinet, Alexandre, E-mail: alexandre.albinet@gmail.com [Institut National de l' Environnement industriel et des RISques (INERIS), Parc Technologique Alata BP2, 60550 Verneuil en Halatte (France)

2016-09-15

21 PAHs, 27 oxy-PAHs and 32 nitro-PAHs were measured every third day over a year in both gaseous (G) and particulate PM{sub 10} (P) phases in ambient air of Grenoble (France). Mean total concentrations (G + P) of PAHs and oxy-PAHs were in the same range and about 10 ng m{sup −3}. Nitro-PAHs were 50 to 100 times less concentrated averaging 100 pg m{sup −3}. Polycyclic aromatic compound (PAC) concentrations were 5 to 7 times higher in “cold” period (October to March) than in “warm” period (April to September). Seasonal variations may be explained by higher primary emissions from residential heating, especially biomass burning in “cold” season. Meteorological conditions and influence of the geomorphology around Grenoble, with the formation of thermal inversion layers leading to the stagnation of pollutants, were additional key parameters. Maximum individual PAC concentrations were observed during two PM{sub 10} pollution events in December and February–March. Chemical processes and secondary formation of oxy- and nitro-PAH were probably enhanced by the accumulation of the pollutants during these events. PAC gas/particle partitioning depended on compound molecular weight and vapour pressure. Gas/particle partitioning of oxy- and nitro-PAHs were evaluated using a multi-phase poly-parameter linear free energy relationship model. The PAC cancer risk was assessed using toxic equivalency factors available in the literature (19 PAHs, 10 nitro-PAHs and 1 oxy-PAH). Overall, particle-bound PACs contributed about 76% of the cancer risk. While PAHs accounted for most of the total PAC cancer risk, oxy- and nitro-PAHs could account for up to 24%. The risk quantification across substance classes is limited by toxicological data availability. - Highlights: • The most comprehensive study about PAH, nitro- and oxy-PAH in ambient air. • 80 species studied in gaseous and particle phases over a year at French urban site. • Concentration seasonality governed by

Helbredsrisici ved eksponering for styren i glasfiberplastindustrien

DEFF Research Database (Denmark)

Kolstad, Henrik Albert; Ebbehøj, Nielse; Bonde, Jens Peter

2012-01-01

system effects with for instance reduced psychological performance, colour discrimination and hearing level following long-term styrene exposure above 10 ppm. There is moderate evidence of a causal association with cancer, but data are not sufficient to allow us to pinpoint specific cancers at risk...

New perspectives of curcumin in cancer prevention

Science.gov (United States)

Park, Wungki; Amin, A.R.M Ruhul; Chen, Zhuo Georgia; Shin, Dong M.

2013-01-01

Numerous natural compounds have been extensively investigated for their potential for cancer prevention over decades. Curcumin, from Curcuma longa, is a highly promising natural compound that can be potentially used for chemoprevention of multiple cancers. Curcumin modulates multiple molecular pathways involved in the lengthy carcinogenesis process to exert its chemopreventive effects through several mechanisms: promoting apoptosis, inhibiting survival signals, scavenging reactive oxidative species (ROS), and reducing the inflammatory cancer microenvironment. Curcumin fulfills the characteristics for an ideal chemopreventive agent with its low toxicity, affordability, and easy accessibility. Nevertheless, the clinical application of curcumin is currently compromised by its poor bioavailability. Here we review the potential of curcumin in cancer prevention, its molecular targets, and action mechanisms. Finally, we suggest specific recommendations to improve its efficacy and bioavailability for clinical applications. PMID:23466484

Clinical trial of pin-point photodynamic therapy using an optic fiber for the improvement of enlarged facial pores: a case study.

Science.gov (United States)

Kim, Sangeun; Cho, Kyeong-Hun

2009-01-01

There are few publications on the treatment options for facial pore size reduction. A focused therapy is needed. To evaluate the efficacy of selective photodynamic therapy (PDT) using an optic fiber for the size reduction of large facial pores. A series of five patients (skin phototypes IV-V) with large facial pores received two successive weekly treatments with an 810-nm diode laser using a fine optic fiber after indocyanine green (ICG) was applied selectively to enlarged pores. Patients were evaluated using digital photography at each treatment session, and at 3 months post-operation. Clinical assessment scores were determined at each treatment session and follow-up visit. Patient satisfaction surveys were obtained at the end of the study. All five participants who completed the 3-month follow-up gave a subjective assessment of reduction of facial pore size. Modest to excellent improvement was achieved. This study demonstrates that treatment with pin-point PDT using an optic fiber is a well-tolerated and effective regimen for the reduction of facial pore size.

Evaluating the Potential Bioactivity of a Novel Compound ER1626

OpenAIRE

Wang, Lijun; Zeng, Yanyan; Wang, Tianling; Liu, Hongyi; Xiao, Hong; Xiang, Hua

2014-01-01

Background ER1626, a novel compound, is a derivate of indeno-isoquinoline ketone. This study was designed to evaluate the biological activity and potential anti-tumor mechanism of ER1626. Method MTT assay, scratch assay and flow cytometry were used to determine cell proliferation, cell migration and cell cycle distribution as well as cell apoptosis on human breast cancer MCF-7 cells and endometrial cancer Ishikawa cells. We also explored the antiangiogenic effect of ER1626 on HUVEC cells and ...

Two novel compounds from the root bark of Morus alba L.

Science.gov (United States)

Li, Ming; Wu, Xuewei; Wang, Xiaoning; Shen, Tao; Ren, Dongmei

2018-01-01

Chemical investigation of the root bark of Morus alba led to the isolation of a new flavone, dioxycudraflavone A (1) and a new 2-arylbenzofuran, 5-hydroxyethyl moracin M (2), together with seven known compounds namely sanggenon V (3), morusin (4), morusignin L (5), licoflavone C (6), moracin C (7), alfafuran (8) and mulberrofuran G (9). The structure elucidation of these compounds was based on analyses of spectroscopic data including 1D, 2D NMR and HR-ESI-MS. All compounds were evaluated for the α-glucosidase inhibitory and cytotoxic activities. Compounds 2-4, 8 and 9 exhibited strong α-glucosidase inhibitory activities with IC 50 less than 10 μM, while only 4 and 9 showed moderate cytotoxic effects against lung cancer cells.

Pharmacokinetics of Dietary Cancer Chemopreventive Compound Dibenzoylmethane in the Rats and Impacts of Nanoemulsion and Genetic knockout of Nrf2 on its Disposition

OpenAIRE

Lin, Wen; Hong, Jin-Liern; Shen, Guoxiang; Wu, Rachel T.; Wu, Yuwen; Huang, Mou-Tuan; Newmark, Harold L.; Huang, Qingrong; Khor, Tin Oo; Heimbach, Tycho; Kong, Ah-Ng

2010-01-01

The pharmacokinetic disposition of a dietary cancer chemopreventive compound dibenzoylmethane (DBM) was studied in male Sprague-Dawley rats after intravenous (i.v.) and oral (p.o.) administrations. Following a single i.v. bolus dose, the mean plasma clearance (CL) of DBM was low as compared to the hepatic blood flow. DBM displayed a high volume of distribution (Vss). The elimination terminal t1/2 was long. The mean CL, Vss and AUC0-∞/dose were similar between the i.v. 10 and 10 mg/kg doses. A...

Iron(III-salophene: an organometallic compound with selective cytotoxic and anti-proliferative properties in platinum-resistant ovarian cancer cells.

Directory of Open Access Journals (Sweden)

Thilo S Lange

2008-05-01

Full Text Available In this pioneer study to the biological activity of organometallic compound Iron(III-salophene (Fe-SP the specific effects of Fe-SP on viability, morphology, proliferation, and cell-cycle progression on platinum-resistant ovarian cancer cell lines were investigated.Fe-SP displayed selective cytotoxicity against SKOV-3 and OVCAR-3 (ovarian epithelial adenocarcinoma cell lines at concentrations between 100 nM and 1 microM, while the viability of HeLa cells (epithelial cervix adenocarcinoma or primary lung or skin fibroblasts was not affected. SKOV-3 cells in contrast to fibroblasts after treatment with Fe-SP revealed apparent hallmarks of apoptosis including densely stained nuclear granular bodies within fragmented nuclei, highly condensed chromatin and chromatin fragmentation. Fe-SP treatment led to the activation of markers of the extrinsic (Caspase-8 and intrinsic (Caspase-9 pathway of apoptosis as well as of executioner Caspase-3 while PARP-1 was deactivated. Fe-SP exerted effects as an anti-proliferative agent with an IC(50 value of 300 nM and caused delayed progression of cells through S-phase phase of the cell cycle resulting in a complete S-phase arrest. When intra-peritoneally applied to rats Fe-SP did not show any systemic toxicity at concentrations that in preliminary trials were determined to be chemotherapeutic relevant doses in a rat ovarian cancer cell model.The present report suggests that Fe-SP is a potent growth-suppressing agent in vitro for cell lines derived from ovarian cancer and a potential therapeutic drug to treat such tumors in vivo.

Berberine Regulated Lipid Metabolism in the Presence of C75, Compound C, and TOFA in Breast Cancer Cell Line MCF-7.

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Tan, Wen; Zhong, Zhangfeng; Wang, Shengpeng; Suo, Zhanwei; Yang, Xian; Hu, Xiaodong; Wang, Yitao

2015-01-01

Berberine interfering with cancer reprogramming metabolism was confirmed in our previous study. Lipid metabolism and mitochondrial function were also the core parts in reprogramming metabolism. In the presence of some energy-related inhibitors, including C75, compound C, and TOFA, the discrete roles of berberine in lipid metabolism and mitochondrial function were elucidated. An altered lipid metabolism induced by berberine was observed under the inhibition of FASN, AMPK, and ACC in breast cancer cell MCF-7. And the reversion of berberine-induced lipid suppression indicated that ACC inhibition might be involved in that process instead of FASN inhibition. A robust apoptosis induced by berberine even under the inhibition of AMPK and lipid synthesis was also indicated. Finally, mitochondrial function regulation under the inhibition of AMPK and ACC might be in an ACL-independent manner. Undoubtedly, the detailed mechanisms of berberine interfering with lipid metabolism and mitochondrial function combined with energy-related inhibitors need further investigation, including the potential compensatory mechanisms for ATP production and the upregulation of ACL.

Berberine Regulated Lipid Metabolism in the Presence of C75, Compound C, and TOFA in Breast Cancer Cell Line MCF-7

Directory of Open Access Journals (Sweden)

Wen Tan

2015-01-01

Full Text Available Berberine interfering with cancer reprogramming metabolism was confirmed in our previous study. Lipid metabolism and mitochondrial function were also the core parts in reprogramming metabolism. In the presence of some energy-related inhibitors, including C75, compound C, and TOFA, the discrete roles of berberine in lipid metabolism and mitochondrial function were elucidated. An altered lipid metabolism induced by berberine was observed under the inhibition of FASN, AMPK, and ACC in breast cancer cell MCF-7. And the reversion of berberine-induced lipid suppression indicated that ACC inhibition might be involved in that process instead of FASN inhibition. A robust apoptosis induced by berberine even under the inhibition of AMPK and lipid synthesis was also indicated. Finally, mitochondrial function regulation under the inhibition of AMPK and ACC might be in an ACL-independent manner. Undoubtedly, the detailed mechanisms of berberine interfering with lipid metabolism and mitochondrial function combined with energy-related inhibitors need further investigation, including the potential compensatory mechanisms for ATP production and the upregulation of ACL.

Anti-lung cancer effects of novel ginsenoside 25-OCH(3)-PPD.

Science.gov (United States)

Wang, Wei; Rayburn, Elizabeth R; Hang, Jie; Zhao, Yuqing; Wang, Hui; Zhang, Ruiwen

2009-09-01

20(S)-25-methoxyl-dammarane-3beta, 12beta, 20-triol (25-OCH(3)-PPD), a newly identified natural product from Panax notoginseng, exhibits activity against a variety of cancer cells. Herein, we report the effects of this compound on human A549, H358, and H838 lung cancer cells, and compare these effects with a control lung epithelial cell line, BEAS-2B. 25-OCH(3)-PPD decreased survival, inhibited proliferation, and induced apoptosis and G1 cell cycle arrest in the lung cancer cell lines. The P. notoginseng compound also decreased the levels of proteins associated with cell proliferation and cell survival. Moreover, 25-OCH(3)-PPD inhibited the growth of A549 lung cancer xenograft tumors. 25-OCH(3)-PPD demonstrated low toxicity to non-cancer cells, and no observable toxicity was seen when the compound was administered to animals. In conclusion, our preclinical data indicate that 25-OCH(3)-PPD is a potential therapeutic agent in vitro and in vivo, and further preclinical and clinical development of this agent for lung cancer is warranted.

MicroRNA dysregulation as a prognostic biomarker in colorectal cancer

International Nuclear Information System (INIS)

Dong, Yujuan; Yu, Jun; Ng, Simon SM

2014-01-01

Colorectal cancer (CRC) is one of the most potentially curable cancers, yet it remains the fourth most common overall cause of cancer death worldwide. The identification of robust molecular prognostic biomarkers can refine the conventional tumor–node–metastasis staging system, avoid understaging of tumor, and help pinpoint patients with early-stage CRC who may benefit from aggressive treatments. Recently, epigenetic studies have provided new molecular evidence to better categorize the CRC subtypes and predict clinical outcomes. In this review, we summarize recent findings concerning the prognostic potential of microRNAs (miRNAs) in CRC. We first discuss the prognostic value of three tissue miRNAs (miR-21-5p, miR-29-3p, miR-148-3p) that have been examined in multiple studies. We also summarize the dysregulation of miRNA processing machinery DICER in CRC and its association with risk for mortality. We also reviewe the potential application of miRNA-associated single-nucleotide polymorphisms as prognostic biomarkers for CRC, especially the miRNA-associated polymorphism in the KRAS gene. Last but not least, we discuss the microsatellite instability-related miRNA candidates. Among all these candidates, miR-21-5p is the most promising prognostic marker, yet further prospective validation studies are required before it can go into clinical usage

Application of the boron neutron capture therapy to undifferentiated thyroid cancer using two boron compounds (BPA and BOPP)

International Nuclear Information System (INIS)

Viaggi, Mabel; Dagrosa, Maria A.; Juvenal, Guillermo J.; Pisarev, Mario A.; Longhino, Juan M.; Blaumann, Hernan R.; Calzetta Larrieu, Osvaldo A.; Kahl, Stephen B.

2004-01-01

We have shown the selective uptake of boronophenylalanine (BPA) by undifferentiated thyroid cancer (UTC) human cell line ARO, both in vitro and in vivo. Moreover, a 50% histologic cure of mice bearing the tumor was observed when the complete boron neutron capture therapy was applied. More recently we have analyzed the biodistribution of BOPP (tetrakis-carborane carboxylate ester of 2,4-bis-(ba-dihydroxyethyl)-deutero-porphyrin IX) and showed that when BOPP was injected 5 days before BPA, and the animals were sacrificed 60 min after the ip injection of BPA, a significant increase in boron uptake by the tumor was found (38-45ppm with both compounds Vs. 20 ppm with BPA alone). Five days post the ip BOPP injection and 1 hr after BPA, the ratios were: tumor/blood 3,75; tumor /distal skin 2. Other important ratios were tumor/thyroid 6,65 and tumor/lung 3,8. The present studies were performed in mice transplanted with ARO cells and injected with BOPP and BPA. Only in mice treated with the neutron beam and injected with the boronated compounds we observed a 100% control of tumor growth. Two groups of mice received different total absorbed doses: 3.00 and 6.01 Gy, but no further improvement in the outcome was found compared to the previous results using BPA alone (4.3 Gy). (author)

Emerging Glycolysis Targeting and Drug Discovery from Chinese Medicine in Cancer Therapy

Directory of Open Access Journals (Sweden)

Zhiyu Wang

2012-01-01

Full Text Available Molecular-targeted therapy has been developed for cancer chemoprevention and treatment. Cancer cells have different metabolic properties from normal cells. Normal cells mostly rely upon the process of mitochondrial oxidative phosphorylation to produce energy whereas cancer cells have developed an altered metabolism that allows them to sustain higher proliferation rates. Cancer cells could predominantly produce energy by glycolysis even in the presence of oxygen. This alternative metabolic characteristic is known as the “Warburg Effect.” Although the exact mechanisms underlying the Warburg effect are unclear, recent progress indicates that glycolytic pathway of cancer cells could be a critical target for drug discovery. With a long history in cancer treatment, traditional Chinese medicine (TCM is recognized as a valuable source for seeking bioactive anticancer compounds. A great progress has been made to identify active compounds from herbal medicine targeting on glycolysis for cancer treatment. Herein, we provide an overall picture of the current understanding of the molecular targets in the cancer glycolytic pathway and reviewed active compounds from Chinese herbal medicine with the potentials to inhibit the metabolic targets for cancer treatment. Combination of TCM with conventional therapies will provide an attractive strategy for improving clinical outcome in cancer treatment.

GRISEOFULVIN ANALOGUES FOR THE TREATMENT OF CANCER BY INHIBITION OF CENTROSOMAL CLUSTERING

DEFF Research Database (Denmark)

2010-01-01

The invention relates to compounds of the formula (I), where the symbols have the meaning given in the specification, for use in a method for treating cancer, to use of these compounds for the manufacture of a pharmaceutical composition for the treatment of cancer, and to methods of treatment...

Bioactive compounds: historical perspectives, opportunities, and challenges.

Science.gov (United States)

Patil, Bhimanagouda S; Jayaprakasha, G K; Chidambara Murthy, K N; Vikram, Amit

2009-09-23

Mom's conventional wisdom of eating fruits and vegetables to lead a healthy life has evolved with scientific, fact-finding research during the past four decades due to advances in science of "Foods for Health". Epidemiological and prospective studies have demonstrated the vital role of fruits, vegetables, and nuts in reducing the risk of cancer and cardiovascular diseases. In recent years, several meta-analyses strongly suggested that by adding one serving of fruits and vegetables to daily diet, the risk of cardiovascular diseases will be decreased up to 7%. The multidisciplinary and partnership efforts of agriculture and medical scientists across the globe stimulated interest in establishing certain interdisciplinary centers and institutes focusing on "Foods for Health". While the consumption of various healthy foods continues, several questions about toxicity, bioavailability, and food-drug interactions of bioactive compounds are yet to be fully understood on the basis of scientific evidence. Recent research on elucidation of the molecular mechanisms to understand the "proof of the concept" will provide the perfect answer when consumers are ready for a "consumer-to-farm" rather than the current "farm-to-consumer" approach. The multidisciplinary research and educational efforts will address the role of healthy foods to improve eye, brain, and heart health while reducing the risk of cancer. Through this connection, this review is an attempt to provide insight and historical perspectives on some of the bioactive compounds from the day of discovery to their current status. The bioactive compounds discussed in this review are flavonoids, carotenoids, curcumin, ascorbic acid, and citrus limonoids.

Garlic and onions: Their cancer prevention properties

Science.gov (United States)

Nicastro, Holly L.; Ross, Sharon A.; Milner, John A.

2015-01-01

The Allium genus includes garlic, onions, shallots, leeks, and chives. These vegetables are popular in cuisines worldwide and are valued for their potential medicinal properties. Epidemiological studies, while limited in their abilities to assess Allium consumption, indicate some associations of Allium vegetable consumption with decreased risk of cancer, particularly cancers of the gastrointestinal tract. Limited intervention studies have been conducted to support these associations. The majority of supportive evidence on Allium vegetables cancer preventive effects comes from mechanistic studies. These studies highlight potential mechanisms of individual sulfur-containing compounds and of various preparations and extracts of these vegetables, including decreased bioactivation of carcinogens, antimicrobial activities, and redox modification. Allium vegetables and their components have effects at each stage of carcinogenesis and affect many biological processes that modify cancer risk. This review discusses the cancer preventive effects of Allium vegetables, particularly garlic and onions, and their bioactive sulfur compounds and highlights research gaps. PMID:25586902

Lung cancer

DEFF Research Database (Denmark)

Hansen, H H; Rørth, M

1999-01-01

The results of the many clinical trials published in 1997 had only modest impact on the treatment results using either cytostatic agents alone or combined with radiotherapy in lung cancer. In SCLC, combination chemotherapy including platin-compounds (cisplatin, carboplatin) and the podophyllotoxins...

Synthesis of Chromonylthiazolidines and Their Cytotoxicity to Human Cancer Cell Lines

Directory of Open Access Journals (Sweden)

Hoang Le Tuan Anh

2015-01-01

Full Text Available Nine new chromonylthiazolidine derivatives were successfully semi-synthesized from paeonol. All of the compounds, including starting materials, the intermediate compound and products, were evaluated for their cytotoxic effects toward eight human cancer cell lines. The synthesized chromonylthiazolidines displayed weak cytotoxic effects against the tested cancer cell lines, but selective cytotoxic effects were observed. Compounds 3a and 3b showed the most selective cytotoxic effects against human epidermoid carcinoma (IC50 44.1 ± 3.6 μg/mL and breast cancer (IC50 32.8 ± 1.4 μg/mL cell lines, respectively. The results suggest that chromoylthiazolidines are potential low-cost, and selective anticancer agents.

Isolation and characterization of an anticancer catechol compound from Semecarpus anacardium.

Science.gov (United States)

Nair, P K Raveedran; Melnick, Steven J; Wnuk, Stanislaw F; Rapp, Magdalena; Escalon, Enrique; Ramachandran, Cheppail

2009-04-21

The fruits and seeds of Semecarpus anacardium are used widely for the treatment of human cancers and other diseases in the Ayurvedic and Sidda systems of medicine in India. The principal aim of this investigation was to isolate and characterize the anticancer compound from the kernel of Semecarpus anacardium nut. The bioactivity-tailored isolation and detailed chemical characterization were used to identify the active compound. Cytotoxicity, apoptosis, cell cycle arrest as well as synergism between the identified anticancer compound and doxorubicin in human tumor cell lines were analyzed. GC/MS, IR, proton NMR, carbon NMR and collisionally induced dissociation (CID) spectra analysis showed that the isolated active compound is 3-(8'(Z),11'(Z)-pentadecadienyl) catechol (SA-3C). SA-3C is cytotoxic to tumor cell lines with IC(50) values lower than doxorubicin and even multidrug resistant tumor cell lines were equally sensitive to SA-3C. SA-3C induced apoptosis in human leukemia cell lines in a dose-dependent manner and showed synergistic cytotoxicity with doxorubicin. The cell cycle arrest induced by SA-3C at S- and G(2)/M-phases correlated with inhibition of checkpoint kinases. SA-3C isolated from the kernel of Semecarpus anacardium can be developed as an important anticancer agent for single agent and/or multiagent cancer therapy.

Domesticating Cancer: An Evolutionary Strategy in the War on Cancer

Directory of Open Access Journals (Sweden)

Gustav van Niekerk

2017-12-01

Full Text Available Since cancer shares the same molecular machinery as the host, most therapeutic interventions that aim to target cancer would inadvertently also adversely affect the host. In addition, cancer continuously evolves, streamlining its host-derived genome for a new single-celled existence. In particular, short-term clinical success observed with most antineoplastic therapies directly relate to the fact that cancer is constantly evolving. However, the clonal evolution of cancer occasionally also render cancer cells uniquely susceptible to therapeutic interventions, as is exemplified by the clinical relevance of synthetic lethality. Synthetic lethality describes a situation where the simultaneous loss of function in two genes results in lethality, but where a loss of function in either single gene is tolerated. This observation suggests that the evolution of cancer, usually seen as a major clinical challenge, may also afford a key opportunity in lowering on-target toxicities accosted with chemotherapy. As an example, by subjecting cancer to specific selection regimes, cancer can in effect be placed on evolutionary trajectories leading to the development of “targetable” phenotypes such as synthetic lethal interactions. However, such a selection regime would have to overcome a range of obstacles such as on-target toxicity and the selection of an evolvable trait. Since the majority of cancer evolution manifests as a loss of function, we suggest that the induction of auxotrophic phenotypes (i.e., where an organism lose the ability to synthesize specific organic compounds required for growth and thus become dependent on it from dietary sources may represent an attractive therapeutic option. As an example, animals can obtain vitamin C either by de novo synthesis or from their diet. However, since the maintenance of synthetic pathways is costly, such pathways are often lost if no longer necessary, resulting in the organism being auxotrophic toward the

Potential anticancer activity of curcumin analogs containing sulfone on human cancer cells

Directory of Open Access Journals (Sweden)

Zhang Qiuyan

2016-01-01

Full Text Available Three curcumin analogs(S1-S3 containing sulfone were investigated for their effects on human prostate cancer PC-3, colon cancer HT-29, lung cancer H1299 and pancreatic cancer BxPC-3 cells. The three compounds were approximately 16-to 96-fold more active than curcumin in these cell lines as determined by the MTT assay. The effects of these compounds on cell growth were further studied in prostate cancer PC-3 cells in both two dimensional (2D and three dimensional (3D cultures. S1-S3strongly inhibited the growth and induced cell death in PC-3 cells, and the effects of these compounds were associated with suppression of nuclear factor kappa B (NF-κB transcriptional activity. Moreover, treatment of PC-3 cells with all three compounds caused a decrease in the level of phosphorylated signal transducer and activator of transcription-3 (p-STAT3 (Tyr705,but not p-STAT3(Ser727. Only S1and S2decreased the presence of phosphorylated Akt (p-Akt in PC-3 cells. These curcumin analogs warrant further in vivo studies for anticancer activities in suitable animal models.

Cytotoxic and Antimigratory Activities of Phenolic Compounds from Dendrobium brymerianum

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Pornprom Klongkumnuankarn

2015-01-01

Full Text Available Chromatographic separation of a methanol extract prepared from the whole plant of Dendrobium brymerianum led to the isolation of eight phenolic compounds. Among the isolated compounds (1–8, moscatilin (1, gigantol (3, lusianthridin (4, and dendroflorin (6 showed appreciable cytotoxicity against human lung cancer cell lines with IC50 values of 196.7, 23.4, 65.0, and 125.8 μg/mL, respectively, and exhibited antimigratory property at nontoxic concentrations. This study is the first report on the biological activities of this plant.

Hybrid optical navigation by crater detection for lunar pin-point landing: trajectories from helicopter flight tests

Science.gov (United States)

Trigo, Guilherme F.; Maass, Bolko; Krüger, Hans; Theil, Stephan

2018-01-01

Accurate autonomous navigation capabilities are essential for future lunar robotic landing missions with a pin-point landing requirement, since in the absence of direct line of sight to ground control during critical approach and landing phases, or when facing long signal delays the herein before mentioned capability is needed to establish a guidance solution to reach the landing site reliably. This paper focuses on the processing and evaluation of data collected from flight tests that consisted of scaled descent scenarios where the unmanned helicopter of approximately 85 kg approached a landing site from altitudes of 50 m down to 1 m for a downrange distance of 200 m. Printed crater targets were distributed along the ground track and their detection provided earth-fixed measurements. The Crater Navigation (CNav) algorithm used to detect and match the crater targets is an unmodified method used for real lunar imagery. We analyze the absolute position and attitude solutions of CNav obtained and recorded during these flight tests, and investigate the attainable quality of vehicle pose estimation using both CNav and measurements from a tactical-grade inertial measurement unit. The navigation filter proposed for this end corrects and calibrates the high-rate inertial propagation with the less frequent crater navigation fixes through a closed-loop, loosely coupled hybrid setup. Finally, the attainable accuracy of the fused solution is evaluated by comparison with the on-board ground-truth solution of a dual-antenna high-grade GNSS receiver. It is shown that the CNav is an enabler for building autonomous navigation systems with high quality and suitability for exploration mission scenarios.

Dietary Supplements and Cancer Treatment: A Risky Mixture

Science.gov (United States)

Some patients with cancer turn to dietary supplements advertised as having anticancer effects or being supportive of general health. But these biologically active compounds may interact dangerously with chemotherapy, radiation, or other cancer treatments.

Cytotoxic compounds from the leaves of Combretum paniculatum Vent

African Journals Online (AJOL)

It is used locally in the treatment of carcinomous tumors. The cytotoxic activity of pheophorbide a and pheophorbide a-methyl ester isolated from the leaves of C. paniculatum were investigated. In vitro cytotoxicity of the compounds were evaluated against HT-29, MCF-7 and HeLa cancer cell lines using the methyl thiazolyl ...

[Compound K suppresses myeloid-derived suppressor cells in a mouse model bearing CT26 colorectal cancer xenograft].

Science.gov (United States)

Wang, Rong; Li, Yalin; Wang, Wuzhou; Zhou, Meijuan; Cao, Zhaohui

2015-05-01

To investigate the effect of ginseng-derived compound K (C-K) on apoptosis, immunosuppressive activity, and pro-inflammatory cytokine production of myeloid-derived suppressor cells (MDSCs) from mice bearing colorectal cancer xenograft. Flow-sorted bone marrow MDSCs from Balb/c mice bearing CT26 tumor xenograft were treated with either C-K or PBS for 96 h and examined for apoptosis with Annexin V/7-AAD, Cox-2 and Arg-1 expressions using qRT-PCR, and supernatant IL-1β, IL-6, and IL-17 levels with ELISA. C-K- or PBS-treated MDSCs were subcutaneously implanted along with CT26 tumor cells in WT Balb/c mice, and the tumor size and morphology were evaluated 21 days later. C-K treatment significantly increased the percentages of early and late apoptotic MDSCs in vitro (Pimmunosuppresive effect of MDSCs to inhibit tumor cell proliferation in mice, which suggests a new strategy of tumor therapy by targeting MDSCs.

Withaferin A and sulforaphane regulate breast cancer cell cycle progression through epigenetic mechanisms.

Science.gov (United States)

Royston, Kendra J; Paul, Bidisha; Nozell, Susan; Rajbhandari, Rajani; Tollefsbol, Trygve O

2018-07-01

Little is known about the effects of combinatorial dietary compounds on the regulation of epigenetic mechanisms involved in breast cancer prevention. The human diet consists of a multitude of components, and there is a need to elucidate how certain compounds interact in collaboration. Withaferin A (WA), found in the Indian winter cherry and documented as a DNA methyltransferase (DNMT) inhibitor, and sulforaphane (SFN), a well-known histone deacetylase (HDAC) inhibitor found in cruciferous vegetables, are two epigenetic modifying compounds that have only recently been studied in conjunction. The use of DNMT and HDAC inhibitors to reverse the malignant expression of certain genes in breast cancer has shown considerable promise. Previously, we found that SFN + WA synergistically promote breast cancer cell death. Herein, we determined that these compounds inhibit cell cycle progression from S to G2 phase in MDA-MB-231 and MCF-7 breast cancer. Furthermore, we demonstrate that this unique combination of epigenetic modifying compounds down-regulates the levels of Cyclin D1 and CDK4, and pRB; conversely, the levels of E2F mRNA and tumor suppressor p21 are increased independently of p53. We find these events coincide with an increase in unrestricted histone methylation. We propose SFN + WA-induced breast cancer cell death is attributed, in part, to epigenetic modifications that result in the modulated expression of key genes responsible for the regulation of cancer cell senescence. Copyright © 2018 Elsevier Inc. All rights reserved.

Qualitative comparison of active compounds between red and green Mariposa Christia Vespertillonis leaves extracts

Science.gov (United States)

Osman, M. S.; Ghani, Z. A.; Ismail, N. F.; Razak, N. A. A.; Jaapar, J.; Ariff, M. A. M.

2017-09-01

At present time, Mariposa Christia Vespertillonis (MCV) leave has become popular for its anti-cancer and thus is used widely among the traditional medicine in Malaysia. There are several types of MCV plants and the one that is currently well-known for traditional medicine in Malaysia is the green MCV (GMCV). Red MCV (RMCV) is another type of MCV plant which can also be found easily in Malaysia. In this study, the active compounds for GMCV and RMCV will be compared and analyzed by using Liquid Chromatography - Mass Spectrometry (LC-MS). The active compounds will be extracted from the MCV leaves by using Supercritical Fluid Extraction (SFE). The findings of this study indicates the global yield of the MCV oils is 31 mg/g while the compound identification indicates the presence of anti-cancer, anti-inflammatory and beneficial phytochemicals. This work is an explorative study to reveal the potential of MCV to be extracted using SFE method as potential therapeutic plants for the traditional medicine in Malaysia.

Colon cancer chemoprevention with ginseng and other botanicals.

OpenAIRE

Wargovich, M J

2001-01-01

Colorectal cancer is becoming increasingly common in Asian countries and still remains the second leading cause of cancer deaths in the United States. Efforts to prevent colon cancer have targeted early detection through screening and chemoprevention. For the last ten years our laboratory has utilized an in vivo screening assay for the testing of potential cancer preventives for colon cancer. We have conducted investigations on over 150 compounds including many with botanical or herbal origin...

Epigenetic diet: impact on the epigenome and cancer

Science.gov (United States)

Hardy, Tabitha M; Tollefsbol, Trygve O

2011-01-01

A number of bioactive dietary components are of particular interest in the field of epigenetics. Many of these compounds display anticancer properties and may play a role in cancer prevention. Numerous studies suggest that a number of nutritional compounds have epigenetic targets in cancer cells. Importantly, emerging evidence strongly suggests that consumption of dietary agents can alter normal epigenetic states as well as reverse abnormal gene activation or silencing. Epigenetic modifications induced by bioactive dietary compounds are thought to be beneficial. Substantial evidence is mounting proclaiming that commonly consumed bioactive dietary factors act to modify the epigenome and may be incorporated into an ‘epigenetic diet’. Bioactive nutritional components of an epigenetic diet may be incorporated into one’s regular dietary regimen and used therapeutically for medicinal or chemopreventive purposes. This article will primarily focus on dietary factors that have been demonstrated to influence the epigenome and that may be used in conjunction with other cancer prevention and chemotherapeutic therapies. PMID:22022340

Synthesis, Antiproliferative, and Multidrug Resistance Reversal Activities of Heterocyclic α,β-Unsaturated Carbonyl Compounds.

Science.gov (United States)

Sun, Ju-Feng; Hou, Gui-Ge; Zhao, Feng; Cong, Wei; Li, Hong-Juan; Liu, Wen-Shuai; Wang, Chunhua

2016-10-01

A series of heterocyclic α,β-unsaturated carbonyl compounds (1a-1d, 2a-2d, 3a-3d, 4a-3d, and 5a-5d) with 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore were synthesized for the development of anticancer and multidrug resistance reverting agents. The antiproliferative activities were tested against nine human cancer cell lines. Approximately 73% of the IC50 values were below 5 μm, while 35% of these figures were submicromolar, and compounds 3a-3d with 4-trifluoro methyl in the arylidene benzene rings were the most potent, since their IC50 values are between 0.06 and 3.09 μm against all cancer cell lines employed. Meanwhile, their multidrug resistance reversal properties and cellular uptake were further examined. The data displayed that all of these compounds could reverse multidrug resistance, particularly, compounds 3a and 4a demonstrated both potent multidrug resistance reverting properties and strong antiproliferative activities, which can be taken as leading molecules for further research of dual effect agents in tumor chemotherapy. © 2016 John Wiley & Sons A/S.

Anti-cancer effects of bioactive compounds from rose hip fruit in human breast cancer cell lines

OpenAIRE

Zhong, Lijie

2017-01-01

Rose hips have long been used in human diets as a food ingredient and supplement. Their multiple medical properties, which have been attributed to their abundant carotenoid composition, have attracted widespread scientific attention. This thesis examined the carotenoid composition in rose hips from five rose species. The anti-cancer effect of different carotenoid fractions from rose hips was investigated in human breast cancer cell lines, using the natural variation in carotenoid content in h...

Nanoencapsulation of bioactive compounds for food applications

OpenAIRE

Sessa, Mariarenata

2012-01-01

2010 - 2011 The increase in dietary-intake-related illnesses, such as obesity, cardiovascular diseases, hypertension, diabetes and cancer, have made in recent years the development of health-and-wellness promoting foods a priority of the food industry. Clinical studies have demonstrated tangible health benefits that may be derived from the intake of bioactive compounds. However many difficulties are associated with their inclusion in food matrices, due to a very low solubility in water and...

The redox biology network in cancer pathophysiology and therapeutics

Directory of Open Access Journals (Sweden)

Gina Manda

2015-08-01

Full Text Available The review pinpoints operational concepts related to the redox biology network applied to the pathophysiology and therapeutics of solid tumors. A sophisticated network of intrinsic and extrinsic cues, integrated in the tumor niche, drives tumorigenesis and tumor progression. Critical mutations and distorted redox signaling pathways orchestrate pathologic events inside cancer cells, resulting in resistance to stress and death signals, aberrant proliferation and efficient repair mechanisms. Additionally, the complex inter-cellular crosstalk within the tumor niche, mediated by cytokines, redox-sensitive danger signals (HMGB1 and exosomes, under the pressure of multiple stresses (oxidative, inflammatory, metabolic, greatly contributes to the malignant phenotype. The tumor-associated inflammatory stress and its suppressive action on the anti-tumor immune response are highlighted. We further emphasize that ROS may act either as supporter or enemy of cancer cells, depending on the context. Oxidative stress-based therapies, such as radiotherapy and photodynamic therapy, take advantage of the cytotoxic face of ROS for killing tumor cells by a non-physiologically sudden, localized and intense oxidative burst. The type of tumor cell death elicited by these therapies is discussed. Therapy outcome depends on the differential sensitivity to oxidative stress of particular tumor cells, such as cancer stem cells, and therefore co-therapies that transiently down-regulate their intrinsic antioxidant system hold great promise. We draw attention on the consequences of the damage signals delivered by oxidative stress-injured cells to neighboring and distant cells, and emphasize the benefits of therapeutically triggered immunologic cell death in metastatic cancer. An integrative approach should be applied when designing therapeutic strategies in cancer, taking into consideration the mutational, metabolic, inflammatory and oxidative status of tumor cells, cellular

Induction of apoptosis in human ovarian cancer cells by new anticancer compounds, epothilone A and B.

Science.gov (United States)

Rogalska, Aneta; Marczak, Agnieszka; Gajek, Arkadiusz; Szwed, Marzena; Śliwińska, Agnieszka; Drzewoski, Józef; Jóźwiak, Zofia

2013-02-01

Epothilones are a new group of compounds with action mechanisms similar to taxanes. The aim of this study was to compare the effects of epothilone A (Epo A) and epothilone B (Epo B) on ovarian cancer cell line SKOV-3 with those of paclitaxel (PTX), a classic taxane. We evaluate glycoprotein P (P-gp) activity in the ovarian cancer cell line. Apoptotic and necrotic cell levels were measured by double staining with Hoechst 33258 and propidium iodide (PI) as well as Annexin V staining. The production of reactive oxygen species (ROS) and changes in mitochondrial membrane potential (ΔΨm) in cells exposed to Epo A, Epo B and PTX were studied using specific fluorescence probes, DCFH(2)-DA (2',7'-dichlorodihydrofluorescein diacetate) and JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine). The cytotoxic activity of the drugs was determined by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) test. All probes were analyzed in both the presence and absence of the antioxidant N-acetylcysteine (NAC). The results obtained demonstrated that the antiproliferative capacity of Epo A and Epo B in SKOV-3 cell line (measured as IC(50) after 72 h continuous treatment) was six and five times greater than that of PTX's respectively. Epothilones induced timecourse-dependent apoptosis and necrosis. Apoptotic and necrotic events were partially blocked by NAC, indicating ROS played a substantial role in epothilone-induced apoptosis. Cell death was also associated with a decrease in mitochondrial membrane potential, which was more pronounced after treatment with epothilones as compared to paclitaxel. Copyright © 2012 Elsevier Ltd. All rights reserved.

The protective effect of some Thai plants and their bioactive compounds in UV light-induced skin carcinogenesis.

Science.gov (United States)

de Silva, Madhura B; Tencomnao, Tewin

2018-05-02

Skin cancer, represents a major public health concern. While the vast majority is non-melanoma skin cancers, melanomas are mostly responsible for mortality. Solar UVB radiation is mutagenic and carcinogenic. It is primarily responsible for both non-melanoma and melanoma skin cancers via excessive production of reactive oxygen species (ROS), which mediate changes in inflammation and immunity, and have been implicated in all three stages of skin cancer development. Due to their regulatory role in numerous functions of cells, signaling pathways are targets for chemoprevention. The current standards in melanoma therapy are targeted and combination therapies, which, albeit prolong survival responses, are still prone to development of drug resistance. To this extent, drugs of natural origin continue to spark great interest. Thailand has a rich biodiversity of indigenous flora, which have traditionally been used to treat a variety of pathologies. The active components in plant extracts that have medicinal properties, termed 'bioactive compounds,' are efficient chemopreventive agents due to their antioxidant, antimutagenic, anticarcinogenic, and carcinogen detoxification properties. Thai plants and their bioactive compounds have shown protective effects on UV light-induced skin cancer in different experimental models. This warrants further in vivo investigations and translation to clinical studies to determine efficacy and safety, for use as lead compounds in targeted/combination therapy or adjuvant therapy with existing regimes. Coupled with a strategy for prevention, this offers a promising outlook for protection against photocarcinogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

Stages of Gastric Cancer

Science.gov (United States)

... liquid that contains barium (a silver-white metallic compound ). The liquid coats the esophagus and stomach, and ... tissues so they can be viewed under a microscope to check for signs of cancer. A biopsy ...

Stages of Esophageal Cancer

Science.gov (United States)

... liquid that contains barium (a silver-white metallic compound ). The liquid coats the esophagus and stomach, and ... remove tissue samples, which are checked under a microscope for signs of cancer. When the esophagus and ...

Coincidence of lung cancer and silicosis in Czechoslovak uranium miners

International Nuclear Information System (INIS)

Urban, S.; Urbanova, S.

1988-01-01

27 patients with established coincidence of lung cancer and silicosis from a group of 1607 cases of lung cancer from radioactive compounds, and 166 cases of pneumoconiosis were reported by the Occupational Diseases Ward of the works Institute of National Health in Uranium Industry in the 1962 to 1986 years. Lung cancer was found in 16% of reported silicosis patients, in 81% it was simple silicosis, in 50% of cases in was an epidermoid type of cancer. In two cases the malignant process originated in the silicotic node, in one case from a tuberculoma. Lung cancer occurred most frequently in the right lower lung region. The mean age of the silicosis group was 48.6 years and 56.0 years for the lung cancer group. No difference was thus seen from the mean age of patients with lung cancer from radioactive compounds diagnosed in the years 1976 to 1980 but it was significantly lower that the reported average age of patients with coincidence of lung cancer and pneumoconiosis in the population not exposed to ionizing radiation. (author). 2 figs., 1 tab., 18 refs

Flavonoids and Wnt/β-Catenin Signaling: Potential Role in Colorectal Cancer Therapies

Directory of Open Access Journals (Sweden)

Nathália G. Amado

2014-07-01

Full Text Available It is now well documented that natural products have played an important role in anticancer therapy. Many studies focus on the ability of these natural compounds to modulate tumor-related signaling pathways and the relationship of these properties to an anticancer effect. According to the World Health Organization (WHO, colorectal cancer (CRC is the third most common cancer and the fourth leading cause of cancer death among men and women. Therefore, finding strategies to fight against CRC is an emergent health problem. CRC has a strong association with deregulation of Wnt/β-catenin signaling pathway. As some types of natural compounds are capable of modulating the Wnt/β-catenin signaling, one important question is whether they could counteract CRC. In this review, we discuss the role of flavonoids, a class of natural compounds, on Wnt/β-catenin regulation and its possible potential for therapeutic usage on colorectal cancer.

Cucurbitacin: Ancient Compound Shedding New Light on Cancer Treatment

Directory of Open Access Journals (Sweden)

Dhong Hyun Lee

2010-01-01

Full Text Available Cucurbitacins and their derivatives are triterpenoids found in medicinal plants known for their diverse pharmacological and biological activities, including anticancer effects, throughout human history. Although initial attention to cucurbitacin as a potential anticancer drug withered for decades, recent discoveries showing that cucurbitacin is a strong STAT3 (Signal Transducers and Activators of Transcription-3 inhibitor have reclaimed the attention of the drug industry one more time. There is increasing evidence showing that some cucurbitacins not only inhibit the JAK-STAT pathway, but also affect other signaling pathways, such as the MAPK pathway, which are also known to be important for cancer cell proliferation and survival. Moreover, some reports have shown the synergistic effect of cucurbitacins with known chemotherapeutic agents, such as doxorubicin and gemcitabine. In this review, we will summarize the recent discoveries regarding molecular mechanisms of action of cucurbitacins in human cancer cells and discuss the possibilities of cucurbitacin as a future anticancer drug in clinical settings.

Cytotoxic cardiac glycosides and other compounds from Asclepias syriaca.

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Araya, Juan J; Kindscher, Kelly; Timmermann, Barbara N

2012-03-23

Phytochemical investigation of the dried biomass of Asclepias syriaca afforded five new compounds (1-5), along with 19 known structures. Overall, the secondary metabolites isolated and identified from this plant showed a wide structural diversity including pentacyclic triterpenes, cardiac glycosides, flavonoid glycosides, lignans, a phenylethanoid, and a glycosylated megastigmane. In addition, the isolates were tested against the cancer breast cell line Hs578T, and those showing IC(50) values lower than 50 μM (1 and 6-9) were further investigated in three additional breast cancer cell lines (MCF-7, T47D, and Sk-Br-3) and the normal breast cell line Hs578Bst.

Exploring the molecular targets of dietary flavonoid fisetin in cancer

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Syed, Deeba N.; Adhami, Vaqar Mustafa; Khan, Naghma; Khan, Mohammad Imran; Mukhtar, Hasan

2016-01-01

The last few decades have seen a resurgence of interest among the scientific community in exploring the efficacy of natural compounds against various human cancers. Compounds of plant origin belonging to different groups such as alkaloids, flavonoids and polyphenols evaluated for their cancer preventive effects have yielded promising data, thereby offering a potential therapeutic alternative against this deadly disease. The flavonol fisetin (3,3′,4′,7-tetrahydroxyflavone), present in fruits a...

In Silico and In Vitro Anticancer Activity of Isolated Novel Marker Compound from Chemically Modified Bioactive Fraction from Curcuma longa (NCCL).

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Naqvi, Arshi; Malasoni, Richa; Gupta, Swati; Srivastava, Akansha; Pandey, Rishi R; Dwivedi, Anil Kumar

2017-10-01

Turmeric ( Curcuma longa ) is reported to possess wide array of biological activities. Herbal Medicament (HM) is a standardized hexane-soluble fraction of C. longa and is well known for its neuroprotective effect. In this study, we attempted to synthesize a novel chemically modified bioactive fraction from HM (NCCL) along with isolation and characterization of a novel marker compound (I). NCCL was prepared from HM. The chemical structure of the marker compound isolated from NCCL was determined from 1D/2D nuclear magnetic resonance, mass spectroscopy, and Fourier transform infrared. The compound so isolated was subjected to in silico and in vitro screenings to test its inhibitory effect on estrogen receptors. Molecular docking studies revealed that the binding poses of the compound I was energetically favorable. Among NCCL and compound I taken for in vitro studies, NCCL had exhibited good anti-cancer activity over compound I against MCF-7, MDA-MB-231, DU-145, and PC-3 cells. This is the first study about the synthesis of a chemically modified bioactive fraction which used a standardized extract since the preparation of the HM. It may be concluded that NCCL fraction having residual components induce more cell death than compound I alone. Thus, NCCL may be used as a potent therapeutic drug. In the present paper, a standardized hexane soluble fraction of Curcuma longa (HM) was chemically modified to give a novel bioactive fraction (NCCL). A novel marker compound was isolated from NCCL and was characerized using various spectral techniques. The compound so isolated was investigated for in-silico screenings. NCCL and isolated compound was subjected to in-vitro anti-cancer screenings against MCF 7, MDA MB 231 (breast adenocarcinoma) and DU 145 and PC 3 cell lines (androgen independent human prostate cancer cells). The virtual screenings reveals that isolated compound has shown favourable drug like properties. NCCL fraction having residual components induces more cell

Targeting Anti-Cancer Active Compounds: Affinity-Based Chromatographic Assays

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de Moraes, Marcela Cristina; Cardoso, Carmen Lucia; Seidl, Claudia; Moaddel, Ruin; Cass, Quezia Bezerra

2016-01-01

Affinity-based chromatography assays encompass the use of solid supports containing immobilized biological targets to monitor binding events in the isolation , identification and/or characterization of bioactive compounds. This powerful bioanalytical technique allows the screening of potential binders through fast analyses that can be directly performed using isolated substances or complex matrices. An overview of the recent researches in frontal and zonal affinity-based chromatography screen...

Imidazoles and benzimidazoles as tubulin-modulators for anti-cancer therapy.

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Torres, Fernando C; García-Rubiño, M Eugenia; Lozano-López, César; Kawano, Daniel F; Eifler-Lima, Vera L; von Poser, Gilsane L; Campos, Joaquín M

2015-01-01

Imidazoles and benzimidazoles are privileged heterocyclic bioactive compounds used with success in the clinical practice of innumerous diseases. Although there are many advancements in cancer therapy, microtubules remain as one of the few macromolecular targets validated for planning active anti-cancer compounds, and the design of drugs that modulate microtubule dynamics in unknown sites of tubulin is one of the goals of the medicinal chemistry. The discussion of the role of new and commercially available imidazole and benzimidazole derivatives as tubulin modulators is scattered throughout scientific literature, and indicates that these compounds have a tubulin modulation mechanism different from that of tubulin modulators clinically available, such as paclitaxel, docetaxel, vincristine and vinblastine. In fact, recent literature indicates that these derivatives inhibit microtubule formation binding to the colchicine site, present good pharmacokinetic properties and are capable of overcoming multidrug resistance in many cell lines. The understanding of the mechanisms involved in the imidazoles/benzimidazoles modulation of microtubule dynamics is very important to develop new strategies to overcome the resistance to anti-cancer drugs and to discover new biomarkers and targets for cancer chemotherapy.

Immense Essence of Excellence: Marine Microbial Bioactive Compounds

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Ira Bhatnagar; Se-Kwon Kim

2010-01-01

Oceans have borne most of the biological activities on our planet. A number of biologically active compounds with varying degrees of action, such as anti-tumor, anti-cancer, anti-microtubule, anti-proliferative, cytotoxic, photo protective, as well as antibiotic and antifouling properties, have been isolated to date from marine sources. The marine environment also represents a largely unexplored source for isolation of new microbes (bacteria, fungi, actinomycetes, microalgae-cyanobacteria and...

Novel Anthra[1,2-c][1,2,5]Thiadiazole-6,11-Diones as Promising Anticancer Lead Compounds: Biological Evaluation, Characterization & Molecular Targets Determination.

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Ahmed Atef Ahmed Ali

Full Text Available The novel compounds NSC745885 and NSC757963 developed at our laboratory were tested against a panel of 60 cancer cell lines at the National Cancer Institute, USA, and a panel of 39 cancer cell lines at the Japanese Foundation of Cancer Research. Both compounds demonstrated selective unique multi-log differential patterns of activity, with GI50 values in the sub-micro molar range against cancer cells rather than normal cardiac cells. NSC757963 showed high selectivity towards the leukemia subpanel. Activities of both compounds strongly correlated to expression of NFKB1 and CSNK2B genes, implying that they may inhibit the NF-κB pathway. Immunocytochemical microscopy of OVCAR-3 cells showed clear cytosolic accumulation of the NF-κB p65 subunit following treatment. Western blotting showed dose dependent inhibition of the nuclear expression of the NF-κB p65 subunit with subsequent accumulation in the cytosol following treatment. Docking experiments showed binding of both compounds to the NF-κB activator IKKβ subunit preventing its translocation to the nucleus. Collectively, these results confirm the ability of our compounds to inhibit the constitutively active NF-κB pathway of OVCAR-3 cells. Furthermore, COMPARE analysis indicated that the activity of NSC757963 is similar to the antituberculosis agent rifamycin SV, this was confirmed by testing the antimycobacterial activity of NSC757963 against Mycobacterium tuberculosis, results revealed potent activity suitable for use in clinical practice. Molecular properties and Lipinski's parameters predicted acceptable bioavailability properties with no indication of mutagenicity, tumorigenicity, irritability and reproductive effects. Oral absorption experiments using the human Caco-2 model showed high intestinal absorption of NSC745885 by passive transport mechanism with no intestinal efflux or active transport mechanisms. The unique molecular characterization as well as the illustrated anticancer

Functional food productions: release the potential of bioactive compounds through food processing

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Epidemiological studies of bioactive compounds from plant-based foods have consistently pointed to undisputed benefits of consumption of plant-based foods on human health particularly regarding cardiovascular diseases and cancers. However, in order to attain the dosage required from these studies, p...

Small-molecule synthetic compound norcantharidin reverses multi-drug resistance by regulating Sonic hedgehog signaling in human breast cancer cells.

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Yu-Jen Chen

Full Text Available Multi-drug resistance (MDR, an unfavorable factor compromising treatment efficacy of anticancer drugs, involves upregulated ATP binding cassette (ABC transporters and activated Sonic hedgehog (Shh signaling. By preparing human breast cancer MCF-7 cells resistant to doxorubicin (DOX, we examined the effect and mechanism of norcantharidin (NCTD, a small-molecule synthetic compound, on reversing multidrug resistance. The DOX-prepared MCF-7R cells also possessed resistance to vinorelbine, characteristic of MDR. At suboptimal concentration, NCTD significantly inhibited the viability of DOX-sensitive (MCF-7S and DOX-resistant (MCF-7R cells and reversed the resistance to DOX and vinorelbine. NCTD increased the intracellular accumulation of DOX in MCF-7R cells and suppressed the upregulated the mdr-1 mRNA, P-gp and BCRP protein expression, but not the MRP-1. The role of P-gp was strengthened by partial reversal of the DOX and vinorelbine resistance by cyclosporine A. NCTD treatment suppressed the upregulation of Shh expression and nuclear translocation of Gli-1, a hallmark of Shh signaling activation in the resistant clone. Furthermore, the Shh ligand upregulated the expression of P-gp and attenuated the growth inhibitory effect of NCTD. The knockdown of mdr-1 mRNA had not altered the expression of Shh and Smoothened in both MCF-7S and MCF-7R cells. This indicates that the role of Shh signaling in MDR might be upstream to mdr-1/P-gp, and similar effect was shown in breast cancer MDA-MB-231 and BT-474 cells. This study demonstrated that NCTD may overcome multidrug resistance through inhibiting Shh signaling and expression of its downstream mdr-1/P-gp expression in human breast cancer cells.

Cyanobacteria as a Source for Novel Anti-Leukemic Compounds.

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Humisto, Anu; Herfindal, Lars; Jokela, Jouni; Karkman, Antti; Bjørnstad, Ronja; Choudhury, Romi R; Sivonen, Kaarina

2016-01-01

Cyanobacteria are an inspiring source of bioactive secondary metabolites. These bioactive agents are a diverse group of compounds which are varying in their bioactive targets, the mechanisms of action, and chemical structures. Cyanobacteria from various environments, especially marine benthic cyanobacteria, are found to be rich sources for the search for novel bioactive compounds. Several compounds with anticancer activities have been discovered from cyanobacteria and some of these have succeeded to enter the clinical trials. Varying anticancer agents are needed to overcome increasing challenges in cancer treatments. Different search methods are used to reveal anticancer compounds from natural products, but cell based methods are the most common. Cyanobacterial bioactive compounds as agents against acute myeloid leukemia are not well studied. Here we examined our new results combined with previous studies of anti-leukemic compounds from cyanobacteria with emphasis to reveal common features in strains producing such activity. We report that cyanobacteria harbor specific anti-leukemic compounds since several studied strains induced apoptosis against AML cells but were inactive against non-malignant cells like hepatocytes. We noted that particularly benthic strains from the Baltic Sea, such as Anabaena sp., were especially potential AML apoptosis inducers. Taken together, this review and re-analysis of data demonstrates the power of maintaining large culture collections for the search for novel bioactivities, and also how anti-AML activity in cyanobacteria can be revealed by relatively simple and low-cost assays.

Human exposure to endocrine disrupting compounds: Their role in reproductive systems, metabolic syndrome and breast cancer. A review.

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Giulivo, Monica; Lopez de Alda, Miren; Capri, Ettore; Barceló, Damià

2016-11-01

Endocrine disrupting chemicals (EDCs) are released into the environment from different sources. They are mainly used in packaging industries, pesticides and food constituents. Clinical evidence, experimental models, and epidemiological studies suggest that EDCs have major risks for humans by targeting different organs and systems in the body (e.g. reproductive system, breast tissue, adipose tissue, pancreas, etc.). Due to the ubiquity of human exposure to these compounds the aim of this review is to describe the most recent data on the effects induced by phthalates, bisphenol A and parabens in a critical window of exposure: in utero, during pregnancy, infants, and children. The interactions and mechanisms of toxicity of EDCs in relation to human general health problems, especially those broadening the term of endocrine disruption to 'metabolic disruption', should be deeply investigated. These include endocrine disturbances, with particular reference to reproductive problems and breast, testicular and ovarian cancers, and metabolic diseases such as obesity or diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical biology drug sensitivity screen identifies sunitinib as synergistic agent with disulfiram in prostate cancer cells.

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Kirsi Ketola

Full Text Available Current treatment options for castration- and treatment-resistant prostate cancer are limited and novel approaches are desperately needed. Our recent results from a systematic chemical biology sensitivity screen covering most known drugs and drug-like molecules indicated that aldehyde dehydrogenase inhibitor disulfiram is one of the most potent cancer-specific inhibitors of prostate cancer cell growth, including TMPRSS2-ERG fusion positive cancers. However, the results revealed that disulfiram alone does not block tumor growth in vivo nor induce apoptosis in vitro, indicating that combinatorial approaches may be required to enhance the anti-neoplastic effects.In this study, we utilized a chemical biology drug sensitivity screen to explore disulfiram mechanistic details and to identify compounds potentiating the effect of disulfiram in TMPRSS2-ERG fusion positive prostate cancer cells. In total, 3357 compounds including current chemotherapeutic agents as well as drug-like small molecular compounds were screened alone and in combination with disulfiram. Interestingly, the results indicated that androgenic and antioxidative compounds antagonized disulfiram effect whereas inhibitors of receptor tyrosine kinase, proteasome, topoisomerase II, glucosylceramide synthase or cell cycle were among compounds sensitizing prostate cancer cells to disulfiram. The combination of disulfiram and an antiangiogenic agent sunitinib was studied in more detail, since both are already in clinical use in humans. Disulfiram-sunitinib combination induced apoptosis and reduced androgen receptor protein expression more than either of the compounds alone. Moreover, combinatorial exposure reduced metastatic characteristics such as cell migration and 3D cell invasion as well as induced epithelial differentiation shown as elevated E-cadherin expression.Taken together, our results propose novel combinatorial approaches to inhibit prostate cancer cell growth. Disulfiram

Polyphenols in Food: Cancer Prevention and Apoptosis Induction.

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Sharma, Ashita; Kaur, Mandeep; Katnoria, Jatinder Kaur; Nagpal, Avinash Kaur

2017-10-06

Polyphenols are group of water-soluble organic compounds, mainly of natural origin. The compounds having about 5-7 aromatic rings and more than 12 phenolic hydroxyl groups are classified as polyphenols. These are the antioxidants which protect the body from oxidative damage. In plants, they are the secondary metabolites produced as a defense mechanism against stress factors. Antioxidant property of polyphenols is suggested to provide protection against many diseases associated with reactive oxygen species (ROS), including cancer. Various studies carried out across the world have suggested that polyphenols can inhibit the tumor generation, induce apoptosis in cancer cells and interfere in progression of tumors. This group of wonder compounds is present in surplus in natural plants and food products. Intake of polyphenols through diet can scavenge ROS and thus can help in cancer prevention. The plant derived products can also be used along with conventional chemotherapy to enhance the chemopreventive effects. The present review focuses on various in vitro and in vivo studies carried out to assess the anti-carcinogenic potential of polyphenols present in our food. Also, the pathways involved in cancer chemopreventive effects of various subclasses (flavonoids, lignans, stilbenes and phenolic acids) of polyphenols are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Synthesis and antiproliferative activity of novel polynuclear heterocyclic compounds derived from 2,3-diaminophenazine.

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Mahran, Asma M; Ragab, Sherif Sh; Hashem, Ahmed I; Ali, Mamdouh M; Nada, Afaf A

2015-01-27

2,3-Diaminophenazine 1 was used as a precursor for the preparation of some novel phenazine derivatives such as imidazo[4,5-b]phenazine-2-thione 2, its methylthio 3, ethyl 1-aryl-3H-[1,2,4]triazolo[2,3-a]imidazo[4,5-b]phenazines 8a-c, ethyl (2Z)-[3-aminophenazin-2-yl)amino](phenylhydrazono)ethanoate 9, pyrazino[2,3-b]phenazine derivatives 10, 12, 15-17, [1,4]diazepino[2,3-b]phenazine derivatives 13, 14, 2,3-dibenzoylaminophenazine 18, 1H-Imidazo[4,5-b]phenazine derivatives 20, 23a-c, 24, 25 and 4-[(E)-(3-amino phenazin-2-yl)diazenyl] derivatives 27-29. All compounds were tested as inhibitors of the proliferation of human lung carcinoma and colorectal cancer cell lines through inhibition of Tyrosine Kinases. Most of compounds exert good activity against the two cancer cell lines. Five compounds (1, 2, 3, 25 and 28) were found to possess the same activity as the standard drug Cisplatin. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Urinary acylcarnitines are altered in human kidney cancer.

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Ganti, Sheila; Taylor, Sandra L; Kim, Kyoungmi; Hoppel, Charles L; Guo, Lining; Yang, Joy; Evans, Christopher; Weiss, Robert H

2012-06-15

Kidney cancer often diagnosed at late stages when treatment options are severely limited. Thus, greater understanding of tumor metabolism leading ultimately to novel approaches to diagnosis is needed. Our laboratory has been utilizing metabolomics to evaluate compounds appearing in kidney cancer patients' biofluids at concentrations different from control patients. Here, we collected urine samples from kidney cancer patients and analyzed them by chromatography coupled to mass spectrometry. Once normalized to control for urinary concentration, samples were analyzed by two independent laboratories. After technical validation, we now show differential urinary concentrations of several acylcarnitines as a function of both cancer status and kidney cancer grade, with most acylcarnitines being increased in the urine of cancer patients and in those patients with high cancer grades. This finding was validated in a mouse xenograft model of human kidney cancer. Biological validation shows carbon chain length-dependent effects of the acylcarnitines on cytotoxicity in vitro, and higher chain length acylcarnitines demonstrated inhibitory effects on NF-κB activation, suggesting an immune modulatory effect of these compounds. Thus, acylcarnitines in the kidney cancer urine may reflect alterations in metabolism, cell component synthesis and/or immune surveillance, and may help explain the profound chemotherapy resistance seen with this cancer. This study shows for the first time the value of a novel class of metabolites which may lead to new therapeutic approaches for cancer and may prove useful in cancer biomarker studies. Furthermore, these findings open up a new area of investigation into the metabolic basis of kidney cancer. Copyright © 2011 UICC.

Meat, dairy, and cancer1234

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Abid, Zaynah; Cross, Amanda J; Sinha, Rashmi

2014-01-01

In 2007 the World Cancer Research Fund and American Institute for Cancer Research (WCRF/AICR) report judged that the evidence for an association between red and processed meat consumption and colorectal cancer was convincing. In addition, the effect of other animal products on cancer risk has been studied, and the WCRF/AICR report concluded that milk probably decreases the risk of colorectal cancer but diets high in calcium probably increase the risk of prostate cancer, whereas there was limited evidence for an association between milk and bladder cancer and insufficient evidence for other cancers. There are several potential mechanisms relating meat to cancer, including heterocyclic amines, polycyclic aromatic hydrocarbons, N-nitroso compounds, and heme iron. Although the evidence in favor of a link between red and processed meat and colorectal cancer is convincing, the relations with other cancers are unclear. In this review, we summarize cohort studies conducted by the National Cancer Institute on meat and dairy intake in relation to cancer since the 2007 WCRF/AICR report. We also report the findings of meta-analyses published since 2007. PMID:24847855

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

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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 breast

Exposure to organic compounds during heat treatment of cooking oils

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Marzena Zaciera

2012-09-01

Full Text Available Fumes from cooking oils were found to be genotoxic in several short-term tests. Epidemiological research among Taiwanese and Chinese women has shown high incidence of lung cancer. These women were not smoking or rarely smoking , but they cooked meals every day. A lot of organic compounds have been identified from cooking oils including PAH.

Discovery of nonsteroidal 17beta-hydroxysteroid dehydrogenase 1 inhibitors by pharmacophore-based screening of virtual compound libraries.

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Schuster, Daniela; Nashev, Lyubomir G; Kirchmair, Johannes; Laggner, Christian; Wolber, Gerhard; Langer, Thierry; Odermatt, Alex

2008-07-24

17Beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) plays a pivotal role in the local synthesis of the most potent estrogen estradiol. Its expression is a prognostic marker for the outcome of patients with breast cancer and inhibition of 17beta-HSD1 is currently under consideration for breast cancer prevention and treatment. We aimed to identify nonsteroidal 17beta-HSD1 inhibitor scaffolds by virtual screening with pharmacophore models built from crystal structures containing steroidal compounds. The most promising model was validated by comparing predicted and experimentally determined inhibitory activities of several flavonoids. Subsequently, a virtual library of nonsteroidal compounds was screened against the 3D pharmacophore. Analysis of 14 selected compounds yielded four that inhibited the activity of human 17beta-HSD1 (IC 50 below 50 microM). Specificity assessment of identified 17beta-HSD1 inhibitors emphasized the importance of including related short-chain dehydrogenase/reductase (SDR) members to analyze off-target effects. Compound 29 displayed at least 10-fold selectivity over the related SDR enzymes tested.

Anti-cancer agents in Saudi Arabian herbals revealed by automated high-content imaging

KAUST Repository

Hajjar, Dina

2017-06-13

Natural products have been used for medical applications since ancient times. Commonly, natural products are structurally complex chemical compounds that efficiently interact with their biological targets, making them useful drug candidates in cancer therapy. Here, we used cell-based phenotypic profiling and image-based high-content screening to study the mode of action and potential cellular targets of plants historically used in Saudi Arabia\\'s traditional medicine. We compared the cytological profiles of fractions taken from Juniperus phoenicea (Arar), Anastatica hierochuntica (Kaff Maryam), and Citrullus colocynthis (Hanzal) with a set of reference compounds with established modes of action. Cluster analyses of the cytological profiles of the tested compounds suggested that these plants contain possible topoisomerase inhibitors that could be effective in cancer treatment. Using histone H2AX phosphorylation as a marker for DNA damage, we discovered that some of the compounds induced double-strand DNA breaks. Furthermore, chemical analysis of the active fraction isolated from Juniperus phoenicea revealed possible anti-cancer compounds. Our results demonstrate the usefulness of cell-based phenotypic screening of natural products to reveal their biological activities.

Metal complexes in cancer therapy – an update from drug design perspective

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Ndagi U

2017-03-01

Full Text Available Umar Ndagi, Ndumiso Mhlongo, Mahmoud E Soliman Molecular Modelling and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, South Africa Abstract: In the past, metal-based compounds were widely used in the treatment of disease conditions, but the lack of clear distinction between the therapeutic and toxic doses was a major challenge. With the discovery of cisplatin by Barnett Rosenberg in 1960, a milestone in the history of metal-based compounds used in the treatment of cancers was witnessed. This forms the foundation for the modern era of the metal-based anticancer drugs. Platinum drugs, such as cisplatin, carboplatin and oxaliplatin, are the mainstay of the metal-based compounds in the treatment of cancer, but the delay in the therapeutic accomplishment of other metal-based compounds hampered the progress of research in this field. Recently, however, there has been an upsurge of activities relying on the structural information, aimed at improving and developing other forms of metal-based compounds and nonclassical platinum complexes whose mechanism of action is distinct from known drugs such as cisplatin. In line with this, many more metal-based compounds have been synthesized by redesigning the existing chemical structure through ligand substitution or building the entire new compound with enhanced safety and cytotoxic profile. However, because of increased emphasis on the clinical relevance of metal-based complexes, a few of these drugs are currently on clinical trial and many more are awaiting ethical approval to join the trial. In this review, we seek to give an overview of previous reviews on the cytotoxic effect of metal-based complexes while focusing more on newly designed metal-based complexes and their cytotoxic effect on the cancer cell lines, as well as on new approach to metal-based drug design and molecular target in cancer therapy. We are optimistic that the concept of selective

P52 Activation and Enzalutamide Therapy in Prostate Cancer

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2017-10-01

c-Myc:hnRNPA1 pathway regulates expression of androgen receptor splice variants and enzalutamide sensitivity in prostate cancer . Castration resistant... prostate cancer (CRPC) remains dependent on androgen receptor (AR) signaling. Alternative splicing of the AR to generate constitutively active... receptor splice variants and enzalutamide sensitivity in prostate cancer . • We discovered that quercetin, a naturally occurring polyphenolic compound

Synthesis, SAR and biological evaluation of a novel series of 1-(2-chloroethyl)-1-nitroso-3-(2-(3-oxobenzoelenazol-2(3H)-yl)ethyl) urea: Organoselenium compounds for cancer therapy.

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Ye, S; Zheng, X; Hu, T; Zeng, H

2016-06-30

Thioredoxin reductase 1 (TrxR1) is an important potential anticancer drug target and closely related to both carcinogenesis and cancer progression. Ethaselen (BBSKE), a novel organoselenium compound inhibiting TrxR1 with selective antitumor effect, while its symmetrical structure results in poor solubility. Carmustine (BCNU), a DNA cross-link agent and also a deactivator of TrxR, is with high toxicity and low selectivity which limit its clinical application to some extents. Herein, a novel compound, 1-(2-chloroethyl)-1-nitroso-3-(2-(3-oxobenzoelenazol-2(3H)-yl)ethyl)urea(4a-1), which was designed through the combination of Ethaselen and Carmustine, showed good solubility, good tagetability, low toxicity and excellent antitumor activity by synergism. Using the structure of 4a-1 as a key active scaffold, a series of novel 1-(2-chloroethyl)-1-nitroso-3-(2-(3-oxobenzoelenazol-2(3H)-yl)ethyl)urea was designed, synthesized and evaluated to explore the structure-activity relationships (SARs) of these inhibitors and to improve their antitumor activities. Notably, 1-(2-chloroethyl)-3-(2-(6-fluoro-3-oxobenzoselenazol-2(3H)-yl)ethyl)-1-nitrosourea(4b-1) was found to exhibit more potent antitumor activities comparable to 4a-1 against all the four cancer cell lines, including Mia PaCa-2, PANC-1, RKO, LoVo. These results have highlighted compound 4b-1 as a new potential lead candidate for future development of novel potent broad-spectrum antitumor agents. In addition, a SAR model was established to conduct further structural modification.

The apoptotic machinery as a biological complex system: analysis of its omics and evolution, identification of candidate genes for fourteen major types of cancer, and experimental validation in CML and neuroblastoma

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Li Destri Giovanni

2009-04-01

Full Text Available Abstract Background Apoptosis is a critical biological phenomenon, executed under the guidance of the Apoptotic Machinery (AM, which allows the physiologic elimination of terminally differentiated, senescent or diseased cells. Because of its relevance to BioMedicine, we have sought to obtain a detailed characterization of AM Omics in Homo sapiens, namely its Genomics and Evolution, Transcriptomics, Proteomics, Interactomics, Oncogenomics, and Pharmacogenomics. Methods This project exploited the methodology commonly used in Computational Biology (i.e., mining of many omics databases of the web as well as the High Throughput biomolecular analytical techniques. Results In Homo sapiens AM is comprised of 342 protein-encoding genes (possessing either anti- or pro-apoptotic activity, or a regulatory function and 110 MIR-encoding genes targeting them: some have a critical role within the system (core AM nodes, others perform tissue-, pathway-, or disease-specific functions (peripheral AM nodes. By overlapping the cancer type-specific AM mutation map in the fourteen most frequent cancers in western societies (breast, colon, kidney, leukaemia, liver, lung, neuroblastoma, ovary, pancreas, prostate, skin, stomach, thyroid, and uterus to their transcriptome, proteome and interactome in the same tumour type, we have identified the most prominent AM molecular alterations within each class. The comparison of the fourteen mutated AM networks (both protein- as MIR-based has allowed us to pinpoint the hubs with a general and critical role in tumour development and, conversely, in cell physiology: in particular, we found that some of these had already been used as targets for pharmacological anticancer therapy. For a better understanding of the relationship between AM molecular alterations and pharmacological induction of apoptosis in cancer, we examined the expression of AM genes in K562 and SH-SY5Y after anticancer treatment. Conclusion We believe that our data

Ghrelin receptor agonists as novel breast cancer therapeutics

OpenAIRE

CHEUK MAN CHERIE AU

2017-01-01

The human cell studies and the live mouse studies are intended to provide the information that is needed to apply therapies to treat breast cancer patients, based on our novel discoveries. We believe that des-acyl ghrelin-like compounds will be novel breast cancer therapeutics while avoiding well-documented serious side effects, including joint pain, osteoporosis or endometrial cancer. Our findings could therefore improve the quality of life of women treated for breast cancer, improve complia...

Antioxidant activity assays on-line with liquid chromatography

NARCIS (Netherlands)

Niederlander, Harm A. G.; van Beek, Teris A.; Bartasiute, Aiste; Koieva, Irina I.

2008-01-01

Screening for antioxidants requires simple in vitro model systems to investigate antioxidant activity. High resolution screening (HRS), combining a separation technique like HPLC with fast post-column (bio)chemical detection can rapidly pinpoint active compounds in complex mixtures. In this paper

Molecular screening of compounds to the predicted Protein-Protein Interaction site of Rb1-E7 with p53- E6 in HPV

Science.gov (United States)

Shaikh, Faraz; Sanehi, Parvish; Rawal, Rakesh

2012-01-01

Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. Human Papillomaviruses (HPVs) which are heterogeneous groups of small double stranded DNA viruses are considered as the primary cause of cervical cancer, involved in 90% of all Cervical Cancers. Two early HPV genes, E6 and E7, are known to play crucial role in tumor formation. E6 binds with p53 and prevents its translocation and thereby inhibit the ability of p53 to activate or repress target genes. E7 binds to hypophosphorylated Rb and thereby induces cells to enter into premature S-phase by disrupting Rb-E2F complexes. The strategy of the research work was to target the site of interaction of Rb1 -E7 & p53-E6. A total of 88 compounds were selected for molecular screening, based on comprehensive literature survey for natural compounds with anti-cancer activity. Molecular docking analysis was carried out with Molegro Virtual Docker, to screen the 88 chosen compounds and rank them according to their binding affinity towards the site of interaction of the viral oncoproteins and human tumor suppressor proteins. The docking result revealed that Nicandrenone a member of Withanolides family of chemical compounds as the most likely molecule that can be used as a candidate drug against HPV induced cervical cancer. Abbreviations HPV - Human Papiloma Virus, HTSP - Human Tumor Suppressor Proteins, VOP - Viral oncoproteins. PMID:22829740

Tetrahydroisoquinolines as novel histone deacetylase inhibitors for treatment of cancer

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Danqi Chen

2016-01-01

Full Text Available Histone acetylation is a critical process in the regulation of chromatin structure and gene expression. Histone deacetylases (HDACs remove the acetyl group, leading to chromatin condensation and transcriptional repression. HDAC inhibitors are considered a new class of anticancer agents and have been shown to alter gene transcription and exert antitumor effects. This paper describes our work on the structural determination and structure-activity relationship (SAR optimization of tetrahydroisoquinoline compounds as HDAC inhibitors. These compounds were tested for their ability to inhibit HDAC 1, 3, 6 and for their ability to inhibit the proliferation of a panel of cancer cell lines. Among these, compound 82 showed the greatest inhibitory activity toward HDAC 1, 3, 6 and strongly inhibited growth of the cancer cell lines, with results clearly superior to those of the reference compound, vorinostat (SAHA. Compound 82 increased the acetylation of histones H3, H4 and tubulin in a concentration-dependent manner, suggesting that it is a broad inhibitor of HDACs.

Statins augment the chemosensitivity of colorectal cancer cells inducing epigenetic reprogramming and reducing colorectal cancer cell 'stemness' via the bone morphogenetic protein pathway

NARCIS (Netherlands)

Kodach, L.L.; Jacobs, R.J.; Voorneveld, P.W.; Wildenberg, M.E.; Verspaget, H.W.; van Wezel, T.; Morreau, H.; Hommes, D.W.; Peppelenbosch, M.P.; van den Brink, G.R.; Hardwick, J.C.H.

2011-01-01

Promoter hypermethylation is an important and potentially reversible mechanism of tumour suppressor gene silencing in cancer. Compounds that demethylate tumour suppressor genes and induce differentiation of cancer cells, but do not have toxic side effects, would represent an exciting option in

New strategies for the treatment of undifferentiated thyroid cancer and poorly differentiated thyroid cancer

International Nuclear Information System (INIS)

Juvenal, Guillermo J.

2006-01-01

Undifferentiated thyroid cancer, which accounts for about 5-10% of thyroid cancer cases, is a very aggressive tumor with no effective treatment, since it lacks iodine uptake and does not respond to radio or chemotherapy. The prognosis of these patients is bad, due to the rapid growth of the tumor and the early development of metastasis. Oncogenes and tumor suppressor genes are involved in the genetic changes that underlie thyroid cancer, as all kinds of tumors. The characterization of these proteins is being exploited to delineate new therapeutic strategies for the treatment of this cancer. This work is focused on those compounds or therapeutic approaches that are being used in clinical essays or in animal models. (author) [es

Prospective study of blood metabolites associated with colorectal cancer risk.

Science.gov (United States)

Shu, Xiang; Xiang, Yong-Bing; Rothman, Nathaniel; Yu, Danxia; Li, Hong-Lan; Yang, Gong; Cai, Hui; Ma, Xiao; Lan, Qing; Gao, Yu-Tang; Jia, Wei; Shu, Xiao-Ou; Zheng, Wei

2018-02-26

Few prospective studies, and none in Asians, have systematically evaluated the relationship between blood metabolites and colorectal cancer risk. We conducted a nested case-control study to search for risk-associated metabolite biomarkers for colorectal cancer in an Asian population using blood samples collected prior to cancer diagnosis. Conditional logistic regression was performed to assess associations of metabolites with cancer risk. In this study, we included 250 incident cases with colorectal cancer and individually matched controls nested within two prospective Shanghai cohorts. We found 35 metabolites associated with risk of colorectal cancer after adjusting for multiple comparisons. Among them, 12 metabolites were glycerophospholipids including nine associated with reduced risk of colorectal cancer and three with increased risk [odds ratios per standard deviation increase of transformed metabolites: 0.31-1.98; p values: 0.002-1.25 × 10 -10 ]. The other 23 metabolites associated with colorectal cancer risk included nine lipids other than glycerophospholipid, seven aromatic compounds, five organic acids and four other organic compounds. After mutual adjustment, nine metabolites remained statistically significant for colorectal cancer. Together, these independently associated metabolites can separate cancer cases from controls with an area under the curve of 0.76 for colorectal cancer. We have identified that dysregulation of glycerophospholipids may contribute to risk of colorectal cancer. © 2018 UICC.

Targeting progesterone metabolism in breast cancer with l-proline derived new 14-azasteroids.

Science.gov (United States)

Singh, Jyotsana; Singh, Ritesh; Gupta, Preeti; Rai, Smita; Ganesher, Asha; Badrinarayan, Preethi; Sastry, G Narahari; Konwar, Rituraj; Panda, Gautam

2017-08-15

Breast cancer cell proliferation is promoted by a variety of mitogenic signals. Classically estrogen is considered as most predominant mitogenic signal in hormone-dependent breast cancer and progesterone is primarily considered to have protective effect. However, it is suggested that some progesterone metabolite may promote breast cancer and progesterone metabolites like 5α-pregnane and 4-pregnene could serve as regulators of estrogen-responsiveness of breast cancer cells. Here, we estimated the potential of alternate targeting of breast cancer via progesterone signalling. l-Proline derived novel 14-azasteroid compounds were screened against MCF-7 and MDA-MB-231 cell lines using MTT assay. In silico studies, cell cycle, Annexin-V-FITC/PI, JC-1 mitochondrial assay, ROS analysis were performed to analyse the impact of hit compound 3b on breast cancer cells. Further, we analysed the impact of hit 3b on the progesterone, its metabolites and enzymes responsible for the conversion of progesterone and its metabolites using ELISA. Data suggests that compound 3b binds and down regulates of 5α-reductase by specifically inhibiting production of progesterone metabolites that are capable of promoting breast cancer proliferation, epithelial mesenchymal transition and migration. This study establishes the proof of concept and generation of new leads for additional targeting of breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Compounding local invariant features and global deformable geometry for medical image registration.

Directory of Open Access Journals (Sweden)

Jianhua Zhang

Full Text Available Using deformable models to register medical images can result in problems of initialization of deformable models and robustness and accuracy of matching of inter-subject anatomical variability. To tackle these problems, a novel model is proposed in this paper by compounding local invariant features and global deformable geometry. This model has four steps. First, a set of highly-repeatable and highly-robust local invariant features, called Key Features Model (KFM, are extracted by an effective matching strategy. Second, local features can be matched more accurately through the KFM for the purpose of initializing a global deformable model. Third, the positional relationship between the KFM and the global deformable model can be used to precisely pinpoint all landmarks after initialization. And fourth, the final pose of the global deformable model is determined by an iterative process with a lower time cost. Through the practical experiments, the paper finds three important conclusions. First, it proves that the KFM can detect the matching feature points well. Second, the precision of landmark locations adjusted by the modeled relationship between KFM and global deformable model is greatly improved. Third, regarding the fitting accuracy and efficiency, by observation from the practical experiments, it is found that the proposed method can improve 6~8% of the fitting accuracy and reduce around 50% of the computational time compared with state-of-the-art methods.

3-Dimensional culture systems for anti-cancer compound profiling and high-throughput screening reveal increases in EGFR inhibitor-mediated cytotoxicity compared to monolayer culture systems.

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Howes, Amy L; Richardson, Robyn D; Finlay, Darren; Vuori, Kristiina

2014-01-01

3-dimensional (3D) culture models have the potential to bridge the gap between monolayer cell culture and in vivo studies. To benefit anti-cancer drug discovery from 3D models, new techniques are needed that enable their use in high-throughput (HT) screening amenable formats. We have established miniaturized 3D culture methods robust enough for automated HT screens. We have applied these methods to evaluate the sensitivity of normal and tumorigenic breast epithelial cell lines against a panel of oncology drugs when cultured as monolayers (2D) and spheroids (3D). We have identified two classes of compounds that exhibit preferential cytotoxicity against cancer cells over normal cells when cultured as 3D spheroids: microtubule-targeting agents and epidermal growth factor receptor (EGFR) inhibitors. Further improving upon our 3D model, superior differentiation of EC50 values in the proof-of-concept screens was obtained by co-culturing the breast cancer cells with normal human fibroblasts and endothelial cells. Further, the selective sensitivity of the cancer cells towards chemotherapeutics was observed in 3D co-culture conditions, rather than as 2D co-culture monolayers, highlighting the importance of 3D cultures. Finally, we examined the putative mechanisms that drive the differing potency displayed by EGFR inhibitors. In summary, our studies establish robust 3D culture models of human cells for HT assessment of tumor cell-selective agents. This methodology is anticipated to provide a useful tool for the study of biological differences within 2D and 3D culture conditions in HT format, and an important platform for novel anti-cancer drug discovery.

General Information about Hypopharyngeal Cancer

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... liquid that contains barium (a silver-white metallic compound ). The liquid coats the esophagus and x-rays ... tissues so they can be viewed under a microscope to check for signs of cancer. Certain factors ...

Treatment Option Overview (Gastric Cancer)

Science.gov (United States)

... liquid that contains barium (a silver-white metallic compound ). The liquid coats the esophagus and stomach, and ... tissues so they can be viewed under a microscope to check for signs of cancer. A biopsy ...

General Information about Esophageal Cancer

Science.gov (United States)

... liquid that contains barium (a silver-white metallic compound ). The liquid coats the esophagus and stomach, and ... remove tissue samples, which are checked under a microscope for signs of cancer. When the esophagus and ...

Radiosensitization of high-Z compounds by medium-energy 160 kV vs. high-energy 6 MV X-rays for radiation therapy: Theoretical, in vitro and in vivo studies of platinum compounds activating glioma F98 cancer cells

Science.gov (United States)

Lim, S.; Pradhan, A.; Nahar, S.; Montenegro, M.; Barth, R.; Nakkula, R.; Turro, C.

2013-03-01

Energy dependence of X-ray irradiation of high-Z compounds for enhanced radiosensitization is explored thoeretically and via in vitro and in vivo experiments. The cell killing ability of medium-energy X-rays from 160 kV source are found to be more effective than 6 MV X-rays in activating high-Z contrast agents. Results are presented for a newly synthesized Pt compound, Pyridine Terpyridine Pt(II) Nitrate ([Pt(typ)(py)]) and carboplatin in treating F98 rat glioma. In-vitro results show considerable reduction in cell viability for radiosensitized cells irradiated with a 160 kV irradiator. Cells treated with 6 MV LINAC radiation find little variation with radiation dose. Maximum dose enhancement factors (DEFs) and minimum cancer cell survival fractions correspond to 50-200 keV range, and fall rapidly at higher energies. Theoretical calculations of photoelectric absorption vis-a-vis total scattering demonstrates this energy dependence. However, in vivo studies of rats treated with [Pt(tpy)(py)] had a severe negative neurotoxic response, confirmed by histopathological analysis. But subsequent in vivo studies using carboplatin showed very positive results in the treatment of F98 glioma bearing rats and potential clinical radiation therapy.

Structural trends in off stoichiometric chalcopyrite type compound semiconductors

Energy Technology Data Exchange (ETDEWEB)

Stephan, Christiane

2011-03-15

Energy supply is one of the most controversial topics that are currently discussed in our global community. Most of the energy delivered to the customer today has its origin in fossil and nuclear power plants. Indefinable risks and the radioactive waste repository problem of the latter as well as the global scarcity of fossil resources cause the renewable energies to grow more and more important for achieving sustainability. The main renewable energy sources are wind power, hydroelectric power and solar energy. On the photovoltaic (PV) market different materials are competing as part of different kinds of technologies, with the largest contribution still coming from wafer based crystalline silicon solar cells (95 %). Until now thin film solar cells only contribute a small portion to the whole PV market, but large capacities are under construction. Thin film photovoltaic shows a number of advantages in comparison to wafer based crystalline silicon PV. Among these material usage and production cost reduction are two prominent examples. The type of PV materials, which are analyzed in this work, are high potential compounds that are widely used as absorber layer in thin film solar cells. These are compound semiconductors of the type CuB{sup III}C{sup VI}{sub 2} (B{sup III} = In, Ga and C{sup VI} = Se, S). Several years of research have already gone into understanding the efficiency limiting factors for solar cell devices fabricated from this compound. Most of the studies concerning electronic defects are done by spectroscopic methods mostly performed using thin films from different kinds of synthesis, without any real knowledge regarding the structural origin of these defects. This work shows a systematic fundamental structural study of intrinsic point defects that are present within the material at various compositions in CuB{sup III}C{sup VI}{sub 2} compound semiconductors. The study is done on reference powder samples with well determined chemical composition and

Structural trends in off stoichiometric chalcopyrite type compound semiconductors

International Nuclear Information System (INIS)

Stephan, Christiane

2011-01-01

Energy supply is one of the most controversial topics that are currently discussed in our global community. Most of the energy delivered to the customer today has its origin in fossil and nuclear power plants. Indefinable risks and the radioactive waste repository problem of the latter as well as the global scarcity of fossil resources cause the renewable energies to grow more and more important for achieving sustainability. The main renewable energy sources are wind power, hydroelectric power and solar energy. On the photovoltaic (PV) market different materials are competing as part of different kinds of technologies, with the largest contribution still coming from wafer based crystalline silicon solar cells (95 %). Until now thin film solar cells only contribute a small portion to the whole PV market, but large capacities are under construction. Thin film photovoltaic shows a number of advantages in comparison to wafer based crystalline silicon PV. Among these material usage and production cost reduction are two prominent examples. The type of PV materials, which are analyzed in this work, are high potential compounds that are widely used as absorber layer in thin film solar cells. These are compound semiconductors of the type CuB III C VI 2 (B III = In, Ga and C VI = Se, S). Several years of research have already gone into understanding the efficiency limiting factors for solar cell devices fabricated from this compound. Most of the studies concerning electronic defects are done by spectroscopic methods mostly performed using thin films from different kinds of synthesis, without any real knowledge regarding the structural origin of these defects. This work shows a systematic fundamental structural study of intrinsic point defects that are present within the material at various compositions in CuB III C VI 2 compound semiconductors. The study is done on reference powder samples with well determined chemical composition and using advanced diffraction techniques

Identification of cancer specific ligands from one-bead one compound combinatorial libraries to develop theranostics agents against oral squamous cell carcinoma

Science.gov (United States)

Yang, Frances Fan

Background: Oral squamous cell carcinoma (OSCC) is one of the most prevalent disease worldwide. One-bead one-compound (OBOC) combinatorial technology is a powerful method to identify peptidomimetic ligands against a variety of receptors on cell surfaces. We therefore hypothesized that cancer specific ligands against OSCC might be identified and can be conjugated to optical dyes or nanocarriers to develop theranostic agents against OSCC. Material and methods: Different OSCC cell lines were incubated with OBOC libraries and beads with cell binding were sorted and then screened with normal human cells to identify peptide-beads binding to different OSCC cell lines but not binding to normal human cells. The molecular probes of OSCC were developed by biotinylating the carboxyl end of the ligands. OSCC theranostic agents were developed by decorating LLY13 with NPs and evaluated by using orthotopic bioluminescent oral cancer model. Results: Six OSCC specific ligands were discovered. Initial peptide-histochemistry study indicated that LLY12 and LLY13 were able to specifically detect OSCC cells grown on chamber slides at the concentration of 1 muM. In addition, LLY13 was found to penetrate into the OSCC cells and accumulate in the cytoplasm, and nucleus. After screened with a panel of integrin antibodies, only anti-alpha3 antibody was able to block most of OSCC cells binding to the LLY13 beads. OSCC theranostic agents developed using targeting LLY13 micelles (25+/- 4nm in diameter) were more efficient in binding to HSC-3 cancer cells compared to non-targeting micelles. Ex vivo images demonstrated that xenografts from the mice with targeting micelles appeared to have higher signals than the non-targeting groups. Conclusion: LLY13 has promising in vitro and in vivo targeting activity against OSCC. In addition, LLY13 is also able to penetrate into cancer cells via endocytosis. Initial study indicated that alpha3 integrin might partially be the corresponding receptor involved

Profiling cancer gene mutations in clinical formalin-fixed, paraffin-embedded colorectal tumor specimens using targeted next-generation sequencing.

Science.gov (United States)

Zhang, Liangxuan; Chen, Liangjing; Sah, Sachin; Latham, Gary J; Patel, Rajesh; Song, Qinghua; Koeppen, Hartmut; Tam, Rachel; Schleifman, Erica; Mashhedi, Haider; Chalasani, Sreedevi; Fu, Ling; Sumiyoshi, Teiko; Raja, Rajiv; Forrest, William; Hampton, Garret M; Lackner, Mark R; Hegde, Priti; Jia, Shidong

2014-04-01

The success of precision oncology relies on accurate and sensitive molecular profiling. The Ion AmpliSeq Cancer Panel, a targeted enrichment method for next-generation sequencing (NGS) using the Ion Torrent platform, provides a fast, easy, and cost-effective sequencing workflow for detecting genomic "hotspot" regions that are frequently mutated in human cancer genes. Most recently, the U.K. has launched the AmpliSeq sequencing test in its National Health Service. This study aimed to evaluate the clinical application of the AmpliSeq methodology. We used 10 ng of genomic DNA from formalin-fixed, paraffin-embedded human colorectal cancer (CRC) tumor specimens to sequence 46 cancer genes using the AmpliSeq platform. In a validation study, we developed an orthogonal NGS-based resequencing approach (SimpliSeq) to assess the AmpliSeq variant calls. Validated mutational analyses revealed that AmpliSeq was effective in profiling gene mutations, and that the method correctly pinpointed "true-positive" gene mutations with variant frequency >5% and demonstrated high-level molecular heterogeneity in CRC. However, AmpliSeq enrichment and NGS also produced several recurrent "false-positive" calls in clinically druggable oncogenes such as PIK3CA. AmpliSeq provided highly sensitive and quantitative mutation detection for most of the genes on its cancer panel using limited DNA quantities from formalin-fixed, paraffin-embedded samples. For those genes with recurrent "false-positive" variant calls, caution should be used in data interpretation, and orthogonal verification of mutations is recommended for clinical decision making.

Doping-assisted low-pressure photoionization mass spectrometry for the real-time detection of lung cancer-related volatile organic compounds.

Science.gov (United States)

Li, Zhen; Xu, Ce; Shu, Jinian; Yang, Bo; Zou, Yao

2017-04-01

Real-time detection of lung cancer-related volatile organic compounds (VOCs) is a promising, non-intrusive technique for lung cancer (LC) prescreening. In this study, a novel method was designed to enhance the detection selectivity and sensitivity of LC-related polar VOCs by dichloromethane (CH 2 Cl 2 ) doping-assisted low-pressure photoionization mass spectrometry (LPPI-MS). Compared with conventional LPPI-MS, CH 2 Cl 2 doping-assisted LPPI-MS boosted the peak intensities of n-propanol, n-pentanal, acetone, and butyl acetate in nitrogen specifically by 53, 18, 16, and 43 times, respectively. The signal intensities of their daughter ions were inhibited or reduced. At relative humidity (RH) of 20%, the sensitivities of n-propanol, n-pentanal, acetone, and butyl acetate detection ranged from 116 to 452 counts/ppbv with a detection time of 10s and R 2 >0.99 for the linear calibration curves. The method was also applicable under higher RH levels of 50% and 90%. Breath samples obtained from 10 volunteers and spiked samples were investigated. Eight-fold enhancements in the signal intensities of polar VOCs were observed in the normal and spiked samples. These preliminary results demonstrate the efficacy of the dichloromethane doping-assisted LPPI technique for the detection of LC-related polar VOCs. Further studies are indispensible to illustrating the detailed mechanism and applying the technique to breath diagnosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Prostate cancer and inflammation: the evidence

Science.gov (United States)

Sfanos, Karen S; De Marzo, Angelo M

2014-01-01

Chronic inflammation is now known to contribute to several forms of human cancer, with an estimated 20% of adult cancers attributable to chronic inflammatory conditions caused by infectious agents, chronic noninfectious inflammatory diseases and / or other environmental factors. Indeed, chronic inflammation is now regarded as an ‘enabling characteristic’ of human cancer. The aim of this review is to summarize the current literature on the evidence for a role for chronic inflammation in prostate cancer aetiology, with a specific focus on recent advances regarding the following: (i) potential stimuli for prostatic inflammation; (ii) prostate cancer immunobiology; (iii) inflammatory pathways and cytokines in prostate cancer risk and development; (iv) proliferative inflammatory atrophy (PIA) as a risk factor lesion to prostate cancer development; and (v) the role of nutritional or other antiinflammatory compounds in reducing prostate cancer risk. PMID:22212087

The Role of Resveratrol in Cancer Therapy

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Jeong-Hyeon Ko

2017-12-01

Full Text Available Abstract: Natural product compounds have recently attracted significant attention from the scientific community for their potent effects against inflammation-driven diseases, including cancer. A significant amount of research, including preclinical, clinical, and epidemiological studies, has indicated that dietary consumption of polyphenols, found at high levels in cereals, pulses, vegetables, and fruits, may prevent the evolution of an array of diseases, including cancer. Cancer development is a carefully orchestrated progression where normal cells acquires mutations in their genetic makeup, which cause the cells to continuously grow, colonize, and metastasize to other organs such as the liver, lungs, colon, and brain. Compounds that modulate these oncogenic processes can be considered as potential anti-cancer agents that may ultimately make it to clinical application. Resveratrol, a natural stilbene and a non-flavonoid polyphenol, is a phytoestrogen that possesses anti-oxidant, anti-inflammatory, cardioprotective, and anti-cancer properties. It has been reported that resveratrol can reverse multidrug resistance in cancer cells, and, when used in combination with clinically used drugs, it can sensitize cancer cells to standard chemotherapeutic agents. Several novel analogs of resveratrol have been developed with improved anti-cancer activity, bioavailability, and pharmacokinetic profile. The current focus of this review is resveratrol’s in vivo and in vitro effects in a variety of cancers, and intracellular molecular targets modulated by this polyphenol. This is also accompanied by a comprehensive update of the various clinical trials that have demonstrated it to be a promising therapeutic and chemopreventive agent.

Review: Biflavonoid compounds of Selaginella Pal. Beauv. and its benefit

Directory of Open Access Journals (Sweden)

AHMAD DWI SETYAWAN

2008-10-01

Full Text Available In the present day, medicinal plants increasingly play important role in human health, while about 60-75% of world population depending on plants and their extracts for medication. Selaginella Pal. Beauv. (Selaginellaceae Reichb. is a potent medicinal plant source. This plant contains biflavonoid compounds, a dimeric form of flavonoids. Flavonoids are secondary metabolite that is most used in medical purposes. They are often occurred in daily consumed vegetables and fruits. Chemical constituents of flavonoids are very diverse, because they are generated in many biosynthetic methods. There are many biflavonoid compounds of Selaginella, i.e. amentoflavone, 2',8''-biapigenin, ginkgetin, heveaflavone, hinokiflavone, isocryptomerine, kayaflavone, podocarpusflavone A, robustaflavone, sumaflavone, and taiwaniaflavone. For the plants, these biflavonoid are used to response environmental condition such as defense against pests, diseases, herbivory, and competitions; while for the people, these compounds are used as antioxidant, anti-inflammatory, anti cancer, antimicrobial (antivirus, antibacterial, anti fungal, antiprotozoan, neuroprotective, vasorelaxant, anti UV-irradiation, antispasmodic, anti allergic, antihaemorrhagic, antinociceptive, etc. The antioxidant purpose of biflavonoid is the most important activities of this secondary metabolite. It is related to the anti cancer and anti-inflammatory functions. The antioxidant of biflavonoid is more powerful than β-carotene, vitamin C and E. In the future, Selaginella research exhaustively needs to be conducted on morphological and molecular characteristics. It deeply needs to explore on biflavonoid and other natural products constituents, and it also needs to search on their bioactivities.

A flavonoid isolated from Streptomyces sp. (ERINLG-4) induces apoptosis in human lung cancer A549 cells through p53 and cytochrome c release caspase dependant pathway.

Science.gov (United States)

Balachandran, C; Sangeetha, B; Duraipandiyan, V; Raj, M Karunai; Ignacimuthu, S; Al-Dhabi, N A; Balakrishna, K; Parthasarathy, K; Arulmozhi, N M; Arasu, M Valan

2014-12-05

The aim of this study was to investigate the anticancer activity of a flavonoid type of compound isolated from soil derived filamentous bacterium Streptomyces sp. (ERINLG-4) and to explore the molecular mechanisms of action. Cytotoxic properties of ethyl acetate extract was carried out against A549 lung cancer cell line using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cytotoxic properties of isolated compound were investigated in A549 lung cancer cell line, COLO320DM cancer cell line and Vero cells. The compound showed potent cytotoxic properties against A549 lung cancer cell line and moderate cytotoxic properties against COLO320DM cancer cell line. Isolated compound showed no toxicity up to 2000 μg/mL in Vero cells. So we have chosen the A549 lung cancer cell line for further anticancer studies. Intracellular visualization was done by using a laser scanning confocal microscope. Apoptosis was measured using DNA fragmentation technique. Treatment of the A549 cancer cells with isolated compound significantly reduced cell proliferation, increased formation of fragmented DNA and apoptotic body. Activation of caspase-9 and caspase-3 indicated that compound may be inducing intrinsic and extrinsic apoptosis pathways. Bcl-2, p53, pro-caspases, caspase-3, caspase-9 and cytochrome c release were detected by western blotting analysis after compound treatment (123 and 164 μM). The activities of pro-caspases-3, caspase-9 cleaved to caspase-3 and caspase-9 gradually increased after the addition of isolated compound. But Bcl-2 protein was down regulated after treatment with isolated compound. Molecular docking studies showed that the compound bound stably to the active sites of caspase-3 and caspase-9. These results strongly suggest that the isolated compound induces apoptosis in A549 cancer cells via caspase activation through cytochrome c release from mitochondria. The present results might provide helpful suggestions for the design of

Gold-Based Medicine: A Paradigm Shift in Anti-Cancer Therapy?

Science.gov (United States)

Yeo, Chien Ing; Ooi, Kah Kooi; Tiekink, Edward R T

2018-06-11

A new era of metal-based drugs started in the 1960s, heralded by the discovery of potent platinum-based complexes, commencing with cisplatin [(H₃N)₂PtCl₂], which are effective anti-cancer chemotherapeutic drugs. While clinical applications of gold-based drugs largely relate to the treatment of rheumatoid arthritis, attention has turned to the investigation of the efficacy of gold(I) and gold(III) compounds for anti-cancer applications. This review article provides an account of the latest research conducted during the last decade or so on the development of gold compounds and their potential activities against several cancers as well as a summary of possible mechanisms of action/biological targets. The promising activities and increasing knowledge of gold-based drug metabolism ensures that continued efforts will be made to develop gold-based anti-cancer agents.

Effect of Wasabi Component 6-(Methylsulfinylhexyl Isothiocyanate and Derivatives on Human Pancreatic Cancer Cells

Directory of Open Access Journals (Sweden)

Yu-Jen Chen

2014-01-01

Full Text Available The naturally occurring compound 6-(methylsulfinylhexyl isothiocyanate (6-MITC was isolated from Wasabia japonica (Wasabi, a pungent spice used in Japanese food worldwide. The synthetic derivatives 6-(methylsulfenylhexyl isothiocyanate (I7447 and 6-(methylsulfonylhexyl isothiocyanate (I7557 are small molecule compounds derived from 6-MITC. This study aimed to evaluate the effect of these compounds on human pancreatic cancer cells. Human pancreatic cancer cell lines PANC-1 and BxPC-3 were used to perform an MTT assay for cell viability and Liu’s stain for morphological observation. The cell cycle was analyzed by DNA histogram. Aldehyde dehydrogenase (ALDH activity was used as a marker for cancer stem cells (CSC. Western blotting was performed for the expression of proteins related to CSC signaling. The results showed that compounds 6-MITC and I7557, but not I7447, inhibited viability of both PANC-1 and BxPC-3 cells. Morphological observation showed mitotic arrest and apoptosis in 6-MITC- and I7557-treated cells. These two compounds induced G2/M phase arrest and hypoploid population. Percentages of ALDH-positive PANC-1 cells were markedly reduced by 6-MITC and I7557 treatment. The expression of CSC signaling molecule SOX2, but not NOTCH1, ABCG2, Sonic hedgehog, or OCT4, was inhibited by 6-MITC and I7557. In conclusion, wasabi compounds 6-MITC and I7557 may possess activity against the growth and CSC phenotypes of human pancreatic cancer cells.

Targeting Apoptosis Pathways in Cancer with Alantolactone and Isoalantolactone

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Azhar Rasul

2013-01-01

Full Text Available Alantolactone and isoalantolactone, main bioactive compounds that are present in many medicinal plants such as Inula helenium, L. Inula japonica, Aucklandia lappa, Inula racemosa, and Radix inulae, have been found to have various pharmacological actions including anti-inflammatory, antimicrobial, and anticancer properties, with no significant toxicity. Recently, the anticancer activity of alantolactone and isoalantolactone has been extensively investigated. Here, our aim is to review their natural sources and their anticancer activity with specific emphasis on mechanism of actions, by which these compounds act on apoptosis pathways. Based on the literature and also on our previous results, alantolactone and isoalantolactone induce apoptosis by targeting multiple cellular signaling pathways that are frequently deregulated in cancers and suggest that their simultaneous targeting by these compounds could result in efficacious and selective killing of cancer cells. This review suggests that alantolactone and isoalantolactone are potential promising anticancer candidates, but additional studies and clinical trials are required to determine their specific intracellular sites of actions and derivative targets in order to fully understand the mechanisms of therapeutic effects to further validate in cancer chemotherapy.

Exploring the physicochemical profile and the binding patterns of selected novel anticancer Himalayan plant derived active compounds with macromolecular targets

Directory of Open Access Journals (Sweden)

Arun Bahadur Gurung

Full Text Available Plants are vital source of compounds offering plethora of therapeutic effects against various ailments without much side effects. Due to wide spread prevalence and drug resistance in cancer; there is an urgent need for discovery of new anti-cancer drugs. In the present study, selected novel anti-cancer plants derived compounds (cmpd1 to cmpd15 from Himalayan region were docked with defined molecular targets that regulate cell proliferation and apoptosis. The binding energies of best docked compounds ranged between −8.0 kcal/mol and −11.71 kcal/mol. Further analysis revealed critical hydrogen bonds and hydrophobic interactions between compounds and targets. The best docked compounds viz., cmpd15 against cyclin-dependent kinase-2 (CDK-2, cmpd8 against CDK-6 and cmpd9 against Topoisomerase I and II showed higher binding affinities than the native co-crystal ligands. The root mean square deviation (RMSD and potential energy plot clearly indicates the stability of the complexes during 20 ns molecular dynamics (MD simulation. The Molecular Mechanics/Poisson Boltzmann Surface Area (MM/PBSA binding energy analysis revealed Van der Waals energy component which is the principal stabilizing energy for their interactions except CDK-2/cmpd15 complex. The polar solvation energy did not have favorable contribution to their stabilization. The binding energy decomposition analysis revealed per residue contribution for each docked complexes. Physicochemical profile studies showed that majority of the compounds conform to Lipinski's rule of five (ROF having low to high blood brain barrier (BBB penetration, human intestinal absorption, plasma binding protein inhibition and P glycoprotein inhibition. Keywords: ADMET, Anticancer, MM/PBSA, Molecular docking, Molecular dynamics simulation and plant derived compounds

Diet Therapy for Cancer Prevention and Treatment Based on Traditional Persian Medicine.

Science.gov (United States)

Javadi, Behjat

2018-04-01

Cancer is the second leading cause of death with profound socio-economic consequences worldwide. Growing evidence suggests the crucial role of diet on cancer prevention and treatment. In Traditional Persian Medicine (TPM) there is a major focus on contribution of special diet and foods to cancer management. In the present article, the cytotoxic and antitumor activities of several food items including plants and animal products recommended by TPM as anticancer agents are discussed. Strong evidence supports the anticancer effects of beetroot (Beta vulgris) and its major compound betanin, cinnamon and cinnamaldehyde, barley (H. vulgare) and its products, extra-virgin olive oil, black pepper (P. nigrum) and its piperine, grapes (V. vinifera) and its compound resveratrol, ginger and its compound 6-gingerol, whey protein, fish, and honey. However, additional pharmacological studies and clinical trials are needed to elucidate their molecular and cellular mechanisms of actions, frequency, and amount of consumption, possible adverse effects, and optimum preparation methods. Moreover, studying mechanisms of actions of the bioactive compounds present in the discussed food items can be helpful in identifying and development of new anticancer agents.

Role of phytochemicals in colon cancer prevention. A nutrigenomics approach

NARCIS (Netherlands)

Erk, van M.J.

2004-01-01

Specific food compounds, especially from fruits and vegetables, may protect against development of colon cancer. In this thesis effects and mechanisms of various phytochemicals in relation to colon cancer prevention were studied through application of large-scale gene expression profiling.

Titanocene–Gold Complexes Containing N-Heterocyclic Carbene Ligands Inhibit Growth of Prostate, Renal, and Colon Cancers in Vitro

Science.gov (United States)

2016-01-01

We report on the synthesis, characterization, and stability studies of new titanocene complexes containing a methyl group and a carboxylate ligand (mba = −OC(O)-p-C6H4-S−) bound to gold(I)–N-heterocyclic carbene fragments through the thiolate group: [(η5-C5H5)2TiMe(μ-mba)Au(NHC)]. The cytotoxicities of the heterometallic compounds along with those of novel monometallic gold–N-heterocyclic carbene precursors [(NHC)Au(mbaH)] have been evaluated against renal, prostate, colon, and breast cancer cell lines. The highest activity and selectivity and a synergistic effect of the resulting heterometallic species was found for the prostate and colon cancer cell lines. The colocalization of both titanium and gold metals (1:1 ratio) in PC3 prostate cancer cells was demonstrated for the selected compound 5a, indicating the robustness of the heterometallic compound in vitro. We describe here preliminary mechanistic data involving studies on the interaction of selected mono- and bimetallic compounds with plasmid (pBR322) used as a model nucleic acid and the inhibition of thioredoxin reductase in PC3 prostate cancer cells. The heterometallic compounds, which are highly apoptotic, exhibit strong antimigratory effects on the prostate cancer cell line PC3. PMID:27182101

Ganoderma spp.: A Promising Adjuvant Treatment for Breast Cancer

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Suárez-Arroyo, Ivette J.; Loperena-Alvarez, Yaliz; Rosario-Acevedo, Raysa; Martínez-Montemayor, Michelle M.

2017-01-01

For the past several decades, cancer patients in the U.S. have chosen the use of natural products as an alternative or complimentary medicine approach to treat or improve their quality of life via reduction or prevention of the side effects during or after cancer treatment. The genus Ganoderma includes about 80 species of mushrooms, of which several have been used for centuries in traditional Asian medicine for their medicinal properties, including anticancer and immunoregulatory effects. Numerous bioactive compounds seem to be responsible for their healing effects. Among the approximately 400 compounds produced by Ganoderma spp., triterpenes, peptidoglycans and polysaccharides are the major physiologically-active constituents. Ganoderma anticancer effects are attributed to its efficacy in reducing cancer cell survival and growth, as well as by its chemosensitizing role. In vitro and in vivo studies have been conducted in various cancer cells and animal models; however, in this review, we focus on Ganoderma’s efficacy on breast cancers. Evidence shows that some species of Ganoderma have great potential as a natural therapeutic for breast cancer. Nevertheless, further studies are needed to investigate their potential in the clinical setting and to translate our basic scientific findings into therapeutic interventions for cancer patients. PMID:28758107

Effect of constituents from samaras of Austroplenckia populnea (Celastraceae) on human cancer cells.

Science.gov (United States)

Caneschi, Carolina Milagres; Muniyappa, Mohan K; Duarte, Lucienir P; Silva, Grácia D F; Dos Santos, Orlando David Henrique; Spillane, Charles; Filho, Sidney Augusto Vieira

2015-01-01

Aiming the continuity of the studies of Austroplenckia populnea, Brazilian species of the Celastraceae family, in the present study, it was investigated the effect of crude extracts obtained with ethanol, ethyl acetate and chloroform and two purified constituents, proanthocyanidin A and 4'-O-methylepigallocatechin, both isolated from its samaras, on cancer cell proliferation assays. The human cancer cells lines MCF-7 (ductal breast carcinoma), A549 (lung cancer), HS578T (ductal breast carcinoma) and non-cancer HEK293 (embryonic kidney cells) were treated with different concentrations of extracts and constituents and the effect was observed through the acid phosphatase method. The chemical structures of the purified compounds were identified by the respective IR and (1)H and (13)C nuclear magnetic resonance spectral data. While crude extracts from samaras of the folk medicine A. populnea can trigger cell proliferative effects in human cell lines, the purified compounds (proanthocyanidin A and 4'-O-methyl-epigallocatechin) isolated from the same extracts can have an opposite (anti-proliferative) effect. Based on the results, it was possible to suggest that extracts from samaras of A. populnea should be further investigated for possible cancer-promoting activities; and the active extracts can also represent a source of compounds that have anti-cancer properties.

Anti-photoaging and Photoprotective Compounds Derived from Marine Organisms

Directory of Open Access Journals (Sweden)

Ramjee Pallela

2010-04-01

Full Text Available Marine organisms form a prominent component of the oceanic population, which significantly contribute in the production of cosmeceutical and pharmaceutical molecules with biologically efficient moieties. In addition to the molecules of various biological activities like anti-bacterial, anti-cancerous, anti-inflammatory and anti-oxidative etc., these organisms also produce potential photoprotective or anti-photoaging agents, which are attracting present day researchers. Continuous exposure to UV irradiation (both UV-A and UV-B leads to the skin cancer and other photoaging complications, which are typically mediated by the reactive oxygen species (ROS, generated in the oxidative pathways. Many of the anti-oxidative and anti-photoaging compounds have been identified previously, which work efficiently against photodamage of the skin. Recently, marine originated photoprotective or anti-photoaging behavior was observed in the methanol extracts of Corallina pilulifera (CPM. These extracts were found to exert potent antioxidant activity and protective effect on UV-A-induced oxidative stress in human dermal fibroblast (HDF cells by protecting DNA and also by inhibiting matrix metalloproteinases (MMPs, a key component in photoaging of the skin due to exposure to UV-A. The present review depicts various other photoprotective compounds from algae and other marine sources for further elaborative research and their probable use in cosmeceutical and pharmaceutical industries.

Redox-Active Selenium Compounds—From Toxicity and Cell Death to Cancer Treatment

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Sougat Misra

2015-05-01

Full Text Available Selenium is generally known as an antioxidant due to its presence in selenoproteins as selenocysteine, but it is also toxic. The toxic effects of selenium are, however, strictly concentration and chemical species dependent. One class of selenium compounds is a potent inhibitor of cell growth with remarkable tumor specificity. These redox active compounds are pro-oxidative and highly cytotoxic to tumor cells and are promising candidates to be used in chemotherapy against cancer. Herein we elaborate upon the major forms of dietary selenium compounds, their metabolic pathways, and their antioxidant and pro-oxidant potentials with emphasis on cytotoxic mechanisms. Relative cytotoxicity of inorganic selenite and organic selenocystine compounds to different cancer cells are presented as evidence to our perspective. Furthermore, new novel classes of selenium compounds specifically designed to target tumor cells are presented and the potential of selenium in modern oncology is extensively discussed.

Assessment of the potential activity of major dietary compounds as selective estrogen receptor modulators in two distinct cell models for proliferation and differentiation

Energy Technology Data Exchange (ETDEWEB)

Lecomte, Sylvain; Lelong, Marie; Bourgine, Gaëlle [Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes (France); Efstathiou, Theo [Laboratoire Nutrinov, Technopole Atalante Champeaux, 8 rue Jules Maillard de la Gournerie, 35012 Rennes Cedex (France); Saligaut, Christian [Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes (France); Pakdel, Farzad, E-mail: farzad.pakdel@univ-rennes1.fr [Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes (France)

2017-06-15

Estrogen receptors (ERs) α and β are distributed in most tissues of women and men. ERs are bound by estradiol (E2), a natural hormone, and mediate the pleiotropic and tissue-specific effects of E2, such as proliferation of breast epithelial cells or protection and differentiation of neuronal cells. Numerous environmental molecules, called endocrine disrupting compounds, also interact with ERs. Phytoestrogens belong to this large family and are considered potent therapeutic molecules that act through their selective estrogen receptor modulator (SERM) activity. Using breast cancer cell lines as a model of estrogen-dependent proliferation and a stably ER-expressing PC12 cell line as a model of neuronal differentiating cells, we studied the SERM activity of major dietary compounds, such as apigenin, liquiritigenin, daidzein, genistein, coumestrol, resveratrol and zearalenone. The ability of these compounds to induce ER-transactivation and breast cancer cell proliferation and enhance Nerve Growth Factor (NGF) -induced neuritogenesis was assessed. Surprisingly, although all compounds were able to activate the ER through an estrogen responsive element reporter gene, they showed differential activity toward proliferation or differentiation. Apigenin and resveratrol showed a partial or no proliferative effect on breast cancer cells but fully contributed to the neuritogenesis effect of NGF. However, daidzein and zearalenone showed full effects on cellular proliferation but did not induce cellular differentiation. In summary, our results suggest that the therapeutic potential of phytoestrogens can diverge depending on the molecule and the phenotype considered. Hence, apigenin and resveratrol might be used in the development of therapeutics for breast cancer and brain diseases. - Highlights: • SERM activity of dietary compounds on proliferation and differentiation is studied. • All the dietary compounds tested transactivate estrogen receptors. • Apigenin and

A New Acetylenic Compound and Other Bioactive Metabolites from a Shark Gill-derived Penicillium Strain

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Yi Zhang

2017-01-01

Full Text Available Nine chiral compounds (1−9 were isolated from the static fermentation culture of a shark gill-derived fungus Penicillium polonicum AP2T1. These compounds include a new acetylenic aromatic ether (1 , (--WA , four alkaloids ( a urantiomide C ( 2 , fructigenine A (3, cyclopenin (4 and cyclopenol (5 and four oxygenated compounds ((R-penipratynolene (6, (3S,4S-3,4-dihydro-3,4,8-trihydroxyl-naphthalenone (7, verrucosidin (8 and norverrucosidin (9. Their structures were elucidated by MS, NMR , optical rotation and circular dichroism (CD . In antimicrobial tests , compounds 1–4, 6 and 8–9 showed weak antibacterial activity against Staphylococcus aureus, Bacillus subtilis, and/or Escherichia coli.Compounds 3, 8 and 9 also exhibited moderate toxicity against Artemia salina larva , and showed cytotoxicity against human colon cancer cell line HCT116.

New Gold(I) Organometallic Compounds with Biological Activity in Cancer Cells

NARCIS (Netherlands)

Bertrand, Benoit; de Almeida, Andreia; van der Burgt, Evelien P. M.; Picquet, Michel; Citta, Anna; Folda, Alessandra; Rigobello, Maria Pia; Le Gendre, Pierre; Bodio, Ewen; Casini, Angela

N-Heterocyclic carbene gold(I) complexes bearing a fluorescent coumarin ligand were synthesized and characterized by various techniques. The compounds were examined for their antiproliferative effects in normal and tumor cells in vitro; they demonstrated moderate activity and a certain degree of

Evaluation of the impact of interdisciplinarity in cancer care

Science.gov (United States)

2011-01-01

Background Teamwork is a key component of the health care renewal strategy emphasized in Quebec, elsewhere in Canada and in other countries to enhance the quality of oncology services. While this innovation would appear beneficial in theory, empirical evidences of its impact are limited. Current efforts in Quebec to encourage the development of local interdisciplinary teams in all hospitals offer a unique opportunity to assess the anticipated benefits. These teams working in hospital outpatient clinics are responsible for treatment, follow-up and patient support. The study objective is to assess the impact of interdisciplinarity on cancer patients and health professionals. Methods/Design This is a quasi-experimental study with three comparison groups distinguished by intensity of interdisciplinarity: strong, moderate and weak. The study will use a random sample of 12 local teams in Quebec, stratified by intensity of interdisciplinarity. The instrument to measure the intensity of the interdisciplinarity, developed in collaboration with experts, encompasses five dimensions referring to aspects of team structure and process. Self-administered questionnaires will be used to measure the impact of interdisciplinarity on patients (health care utilization, continuity of care and cancer services responsiveness) and on professionals (professional well-being, assessment of teamwork and perception of teamwork climate). Approximately 100 health professionals working on the selected teams and 2000 patients will be recruited. Statistical analyses will include descriptive statistics and comparative analysis of the impact observed according to the strata of interdisciplinarity. Fixed and random multivariate statistical models (multilevel analyses) will also be used. Discussion This study will pinpoint to what extent interdisciplinarity is linked to quality of care and meets the complex and varied needs of cancer patients. It will ascertain to what extent interdisciplinary teamwork

GRISEOFULVIN ANALOGUES FOR THE TREATMENT OF CANCER BY INHIBITION OF CENTROSOMAL CLUSTERING

DEFF Research Database (Denmark)

2008-01-01

The present invention relates to uses of compounds having a structure as shown by formula (I) for the manufacture of a pharmaceutical composition for the treatment of cancer. Moreover, the present invention encompasses methods of treatment for said diseases.......The present invention relates to uses of compounds having a structure as shown by formula (I) for the manufacture of a pharmaceutical composition for the treatment of cancer. Moreover, the present invention encompasses methods of treatment for said diseases....

The in Vitro Structure-Related Anti-Cancer Activity of Ginsenosides and Their Derivatives

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Liang Liu

2011-12-01

Full Text Available Panax ginseng has long been used in Asia as a herbal medicine for the prevention and treatment of various diseases, including cancer. The current study evaluated the cytotoxic potency against a variety of cancer cells by using ginseng ethanol extracts (RSE, protopanaxadiol (PPD-type, protopanaxatriol (PPT-type ginsenosides fractions, and their hydrolysates, which were prepared by stepwise hydrolysis of the sugar moieties of the ginsenosides. The results showed that the cytotoxic potency of the hydrolysates of RSE and total PPD-type or PPT-type ginsenoside fractions was much stronger than the original RSE and ginsenosides; especially the hydrolysate of PPD-type ginsenoside fractions. Subsequently, two derivatives of protopanaxadiol (1, compounds 2 and 3, were synthesized via hydrogenation and dehydration reactions of compound 1. Using those two derivatives and the original ginsenosides, a comparative study on various cancer cell lines was conducted; the results demonstrated that the cytotoxic potency was generally in the descending order of compound 3 > 20(S-dihydroprotopanaxadiol (2 > PPD (1 > 20(S-Rh2 > 20(R-Rh2 ≈ 20(R-Rg3 ≈ 20(S-Rg3. The results clearly indicate the structure-related activities in which the compound with less polar chemical structures possesses higher cytotoxic activity towards cancer cells.

Synthesis and structure-activity relationship exploration of some potent anti-cancer phenyl amidrazone derivatives.

Science.gov (United States)

Habashneh, Almeqdad Y; El-Abadelah, Mustafa M; Bardaweel, Sanaa K; Taha, Mutasem O

2017-12-04

Amidrazones have been reported to have significant anti-tumor properties against several cancer cell lines. The current project aims to profile the structure-anticancer activity relationship of phenyl-amidrazons. Fifteen phenyl-amidrazone-piperazine derivatives were prepared and tested against four cancer cell lines (leukemia, prostate, breast and colon cancers). Six compounds illustrated low micromolar anticancer IC50 values, while the remaining compounds were either inactive or of moderate potencies. All compounds were virtually nontoxic against normal fibroblast cells. Docking into the oncogenic kinase bcr/abl illustrated the critical importance of (i) p-halogen substituent on the ligand's phenyl ring and (ii) the presence of positive ionizable moiety at the ligand's piperazine fragment for anticancer activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Fused Heterocyclic Compounds as Potent Indoleamine-2,3-dioxygenase 1 Inhibitors.

Science.gov (United States)

Panda, Subhankar; Roy, Ashalata; Deka, Suman Jyoti; Trivedi, Vishal; Manna, Debasis

2016-12-08

Uncontrolled metabolism of l-tryptophan (l-Trp) in the immune system has been recognized as a critical cellular process in immune tolerance. Indoleamine 2,3-dioxygenase 1 (IDO1) enzyme plays an important role in the metabolism of a local l-Trp through the kynurenine pathway in the immune systems. In this regard, IDO1 has emerged as a therapeutic target for the treatment of diseases that are associated with immune suppression like chronic infections, cancer, and others. In this study, we synthesized a series of pyridopyrimidine, pyrazolopyranopyrimidine, and dipyrazolopyran derivatives. Further lead optimizations directed to the identification of potent compounds, 4j and 4l (IC 50 = 260 and 151 nM, respectively). These compounds also exhibited IDO1 inhibitory activities in the low nanomolar range in MDA-MB-231 cells with very low cytotoxicity. Stronger selectivity for the IDO1 enzyme (>300-fold) over tryptophan 2,3-dioxygenase (TDO) enzyme was also observed for these compounds. Hence, these fused heterocyclic compounds are attractive candidates for the advanced study of IDO1-dependent cellular function and immunotherapeutic applications.

Early onset of colorectal cancer in a 13-year-old girl with Lynch syndrome.

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Ahn, Do Hee; Rho, Jung Hee; Tchah, Hann; Jeon, In-Sang

2016-01-01

Lynch syndrome is the most common inherited colon cancer syndrome. Patients with Lynch syndrome develop a range of cancers including colorectal cancer (CRC) and carry a mutation on one of the mismatched repair (MMR) genes. Although CRC usually occurs after the fourth decade in patients with Lynch syndrome harboring a heterozygous MMR gene mutation, it can occur in children with Lynch syndrome who have a compound heterozygous or homozygous MMR gene mutation. We report a case of CRC in a 13-year-old patient with Lynch syndrome and congenital heart disease. This patient had a heterozygous mutation in MLH1 (an MMR gene), but no compound MMR gene defects, and a K-RAS somatic mutation in the cancer cells.

Natural Compounds from Herbs that can Potentially Execute as Autophagy Inducers for Cancer Therapy

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Shian-Ren Lin

2017-07-01

Full Text Available Accumulated evidence indicates that autophagy is a response of cancer cells to various anti-cancer therapies. Autophagy is designated as programmed cell death type II, and is characterized by the formation of autophagic vacuoles in the cytoplasm. Numerous herbs, including Chinese herbs, have been applied to cancer treatments as complementary and alternative medicines, supplements, or nutraceuticals to dampen the side or adverse effects of chemotherapy drugs. Moreover, the tumor suppressive actions of herbs and natural products induced autophagy that may lead to cell senescence, increase apoptosis-independent cell death or complement apoptotic processes. Hereby, the underlying mechanisms of natural autophagy inducers are cautiously reviewed in this article. Additionally, three natural compounds—curcumin, 16-hydroxycleroda-3,13-dien-15,16-olide, and prodigiosin—are presented as candidates for autophagy inducers that can trigger cell death in a supplement or alternative medicine for cancer therapy. Despite recent advancements in therapeutic drugs or agents of natural products in several cancers, it warrants further investigation in preclinical and clinical studies.

The scent of colorectal cancer: detection by volatile organic compound analysis

NARCIS (Netherlands)

de Boer, Nanne K. H.; de Meij, Tim G. J.; Oort, Frank A.; Ben Larbi, Ilhame; Mulder, Chris J. J.; van Bodegraven, Adriaan A.; van der Schee, Marc P.

2014-01-01

The overall metabolic state of an individual is reflected by emitted volatile organic compounds (VOCs), which are gaseous carbon-based chemicals. In this review, we will describe the potential of VOCs as fully noninvasive markers for the detection of neoplastic lesions of the colon. VOCs are

Targeting Epithelial-Mesenchymal Transition for Identification of Inhibitors for Pancreatic Cancer Cell Invasion and Tumor Spheres Formation.

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Kishore Polireddy

Full Text Available Pancreatic cancer has an enrichment of stem-like cancer cells (CSCs that contribute to chemoresistant tumors prone to metastasis and recurrence. Drug screening assays based on cytotoxicity cannot identify specific CSC inhibitors, because CSCs comprise only a small portion of cancer cell population, and it is difficult to propagate stable CSC populations in vitro for high-throughput screening (HTS assays. Based on the important role of cancer cell epithelial-to-mesenchymal transition (EMT in promoting CSCs, we hypothesized that inhibition of EMT can be a useful strategy for inhibiting CSCs, and therefore a feasible approach for HTS can be built for identification of CSC inhibitors, based on assays detecting EMT inhibition.An immunofluorescent assay was established and optimized for HTS to identify compounds that enhance E-cadherin expression, as a hallmark of inhibition of EMT. Four chemical libraries containing 41,472 compounds were screened in PANC-1 pancreatic cancer cell line. Positive hits were validated for EMT and CSC inhibition in vitro using sphere formation assay, western blotting, immune fluorescence, and scratch assay.Initial hits were refined to 73 compounds with a secondary screening, among which 17 exhibited concentration dependent induction of E-cadherin expression. Six compounds were selected for further study which belonged to 2 different chemical structural clusters. A novel compound 1-(benzylsulfonyl indoline (BSI, Compound #38 significantly inhibited pancreatic cancer cell migration and invasion. BSI inhibited histone deacetylase, increased histone 4 acetylation preferably, resulting in E-cadherin up-regulation. BSI effectively inhibited tumor spheres formation. Six more analogues of BSI were tested for anti-migration and anti-CSC activities.This study demonstrated a feasible approach for discovery of agents targeting EMT and CSCs using HTS, and identified a class of novel chemicals that could be developed as anti-EMT and

Primary and acquired resistance to biologic therapies in gastrointestinal cancers.

Science.gov (United States)

Lubner, Sam J; Uboha, Nataliya V; Deming, Dustin A

2017-06-01

Improvements in the understanding of cancer biology have led to therapeutic advances in the treatment of gastrointestinal cancers. Drugs which target the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways have led the way in colon cancer. Monoclonal antibodies (mAbs) such as bevacizumab, ramucirumab, cetuximab, and panitumumab, have improved progression free survival and overall survival (OS) for colorectal cancers and were quickly adopted. Human epidermal growth factor receptor 2 (HER2) has demonstrated significant benefit for gastroesophageal cancers and in the setting of HER2 amplification, trastuzumab in combination with chemotherapy has become the standard of care. However, responses have not been as durable nor as robust as once hoped. Mechanisms of resistance for each of these biologic compounds have been hypothesized and are in the process of being better elucidated. This review will approach the innate and acquired mechanisms of resistance of the above compounds. Additionally, we will explore some ongoing clinical trials to capitalize on the mechanisms of resistance in the hopes of retaining the promise of targeting these pathways.

Prediction of drug efficacy for cancer treatment based on comparative analysis of chemosensitivity and gene expression data

DEFF Research Database (Denmark)

Wan, Peng; Li, Qiyuan; Larsen, Jens Erik Pontoppidan

2012-01-01

The NCI60 database is the largest available collection of compounds with measured anti-cancer activity. The strengths and limitations for using the NCI60 database as a source of new anti-cancer agents are explored and discussed in relation to previous studies. We selected a sub-set of 2333...... and in a data set of expression profiles of 1901 genes for the corresponding tumor cell lines. Five clusters were identified based on the gene expression data using self-organizing maps (SOM), comprising leukemia, melanoma, ovarian and prostate, basal breast, and luminal breast cancer cells, respectively....... The strong difference in gene expression between basal and luminal breast cancer cells was reflected clearly in the chemosensitivity data. Although most compounds in the data set were of low potency, high efficacy compounds that showed specificity with respect to tissue of origin could be found. Furthermore...

Nanoencapsulation of polyphenols for protective effect against colon-rectal cancer.

Science.gov (United States)

Santos, Isis S; Ponte, Bruno M; Boonme, Prapaporn; Silva, Amélia M; Souto, Eliana B

2013-01-01

The human population at large is exposed to many critical factors (e.g. bad food habits, chemical substances, and stress) leading to the development of serious diseases. Colon or colorectal cancer is one of the most prevalent types of cancer in many countries. Despite being a multi-factorial chronic disease, resulting from the interaction of multiple genetic and environmental factors, the critical factor is mostly a poor diet regimen. Therefore, an accumulation of constant mutations leads to a complex arrangement of events during tumor initiation, development and propagation. It is well known that many plants are rich in polyphenols with anti-oxidant, anti-atherogenic, anti-diabetic, anti-cancer, anti-viral, and anti-inflammatory properties. These compounds are secondary metabolites with the ability to donate electrons to free radicals through different mechanisms. In recent years, a large number of studies have attributed a protective effect to polyphenols and foods containing these compounds (e.g. plants, vegetables, cereals, tea, coffee or chocolate). Polyphenolic compounds have been described to inhibit cancer development and propagation, being used as chemopreventive agents. Some polyphenols reported a preventive action against colon cancer, e.g. curcumin, gallic acid, ellagic acid, and epigallocatechin-3-gallate. The present article focuses on the properties of these molecules as chemopreventive agents and the recent advances on their formulation in nanoparticulate systems for targeted therapy and increased bioavailability. Copyright © 2012 Elsevier Inc. All rights reserved.

Exploiting Epigenetic Alterations in Prostate Cancer.

Science.gov (United States)

Baumgart, Simon J; Haendler, Bernard

2017-05-09

Prostate cancer affects an increasing number of men worldwide and is a leading cause of cancer-associated deaths. Beside genetic mutations, many epigenetic alterations including DNA and histone modifications have been identified in clinical prostate tumor samples. They have been linked to aberrant activity of enzymes and reader proteins involved in these epigenetic processes, leading to the search for dedicated inhibitory compounds. In the wake of encouraging anti-tumor efficacy results in preclinical models, epigenetic modulators addressing different targets are now being tested in prostate cancer patients. In addition, the assessment of microRNAs as stratification biomarkers, and early clinical trials evaluating suppressor microRNAs as potential prostate cancer treatment are being discussed.

Exploiting Epigenetic Alterations in Prostate Cancer

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Simon J. Baumgart

2017-05-01

Full Text Available Prostate cancer affects an increasing number of men worldwide and is a leading cause of cancer-associated deaths. Beside genetic mutations, many epigenetic alterations including DNA and histone modifications have been identified in clinical prostate tumor samples. They have been linked to aberrant activity of enzymes and reader proteins involved in these epigenetic processes, leading to the search for dedicated inhibitory compounds. In the wake of encouraging anti-tumor efficacy results in preclinical models, epigenetic modulators addressing different targets are now being tested in prostate cancer patients. In addition, the assessment of microRNAs as stratification biomarkers, and early clinical trials evaluating suppressor microRNAs as potential prostate cancer treatment are being discussed.

Elucidation of the antibacterial mechanism of the Curvularia haloperoxidase system by DNA microarray profiling

DEFF Research Database (Denmark)

Hansen, E.H.; Schembri, Mark; Klemm, Per

2004-01-01

was the wild type. Our results demonstrate that DNA microarray technology cannot be used as the only technique to investigate the mechanisms of action of new antimicrobial compounds. However, by combining DNA microarray analysis with the subsequent creation of knockout mutants, we were able to pinpoint one...

Understanding drugs in breast cancer through drug sensitivity screening.

Science.gov (United States)

Uhr, Katharina; Prager-van der Smissen, Wendy J C; Heine, Anouk A J; Ozturk, Bahar; Smid, Marcel; Göhlmann, Hinrich W H; Jager, Agnes; Foekens, John A; Martens, John W M

2015-01-01

With substantial numbers of breast tumors showing or acquiring treatment resistance, it is of utmost importance to develop new agents for the treatment of the disease, to know their effectiveness against breast cancer and to understand their relationships with other drugs to best assign the right drug to the right patient. To achieve this goal drug screenings on breast cancer cell lines are a promising approach. In this study a large-scale drug screening of 37 compounds was performed on a panel of 42 breast cancer cell lines representing the main breast cancer subtypes. Clustering, correlation and pathway analyses were used for data analysis. We found that compounds with a related mechanism of action had correlated IC50 values and thus grouped together when the cell lines were hierarchically clustered based on IC50 values. In total we found six clusters of drugs of which five consisted of drugs with related mode of action and one cluster with two drugs not previously connected. In total, 25 correlated and four anti-correlated drug sensitivities were revealed of which only one drug, Sirolimus, showed significantly lower IC50 values in the luminal/ERBB2 breast cancer subtype. We found expected interactions but also discovered new relationships between drugs which might have implications for cancer treatment regimens.

Effect of constituents from samaras of Austroplenckia populnea (Celastraceae on human cancer cells

Directory of Open Access Journals (Sweden)

Carolina Milagres Caneschi

2015-03-01

Full Text Available Background. Aiming the continuity of the studies of Austroplenckia populnea, Brazilian species of the Celastraceae family, in the present study was investigated the effect of crude extracts obtained with ethanol, ethyl acetate and chloroform and two purified constituents, proanthocyanidin A and 4'-O-methylepigallocatechin, both isolated from its samaras, on cancer cell proliferation assays. Material and methods. The human cancer cells lines MCF-7 (ductal breast carcinoma, A549 (lung cancer, HS578T (ductal breast carcinoma and non-cancer HEK293 (embryonic kidney cells were treated with different concentration of extracts and constituents and the effect was observed through acid phosphatase method. The chemical structures of the purified compounds were identified by the respective IR and 1H and 13C NMR spectral data. Results. While crude extracts from samaras of the folk medicine A. populnea can trigger cell proliferative effects in human cell lines, the purified compounds (Proanthocyanidin A and 4'-O-methyl-epigallocatechin isolated from the same extracts can have an opposite (anti-proliferative effect. Conclusion. Based on the results was possible to suggest that extracts from samaras of A. populnea should be investigated further for possible cancer-promoting activities; such extracts can also represent a source of compounds that have anti-cancer properties. [J Intercult Ethnopharmacol 2015; 4(1.000: 6-11

Disruption of focal adhesion kinase and p53 interaction with small molecule compound R2 reactivated p53 and blocked tumor growth

International Nuclear Information System (INIS)

Golubovskaya, Vita M; Ho, Baotran; Zheng, Min; Magis, Andrew; Ostrov, David; Morrison, Carl; Cance, William G

2013-01-01

Focal Adhesion Kinase (FAK) is a 125 kDa non-receptor kinase that plays a major role in cancer cell survival and metastasis. We performed computer modeling of the p53 peptide containing the site of interaction with FAK, predicted the peptide structure and docked it into the three-dimensional structure of the N-terminal domain of FAK involved in the complex with p53. We screened small molecule compounds that targeted the site of the FAK-p53 interaction and identified compounds (called Roslins, or R compounds) docked in silico to this site. By different assays in isogenic HCT116p53 + / + and HCT116 p53 - / - cells we identified a small molecule compound called Roslin 2 (R2) that bound FAK, disrupted the binding of FAK and p53 and decreased cancer cell viability and clonogenicity in a p53-dependent manner. In addition, dual-luciferase assays demonstrated that the R2 compound increased p53 transcriptional activity that was inhibited by FAK using p21, Mdm-2, and Bax-promoter targets. R2 also caused increased expression of p53 targets: p21, Mdm-2 and Bax proteins. Furthermore, R2 significantly decreased tumor growth, disrupted the complex of FAK and p53, and up-regulated p21 in HCT116 p53 + / + but not in HCT116 p53 - / - xenografts in vivo. In addition, R2 sensitized HCT116p53 + / + cells to doxorubicin and 5-fluorouracil. Thus, disruption of the FAK and p53 interaction with a novel small molecule reactivated p53 in cancer cells in vitro and in vivo and can be effectively used for development of FAK-p53 targeted cancer therapy approaches

A cohort study of intra-urban variations in volatile organic compounds and mortality, Toronto, Canada

International Nuclear Information System (INIS)

Villeneuve, Paul J.; Jerrett, Michael; Su, Jason; Burnett, Richard T.; Chen, Hong; Brook, Jeffrey; Wheeler, Amanda J.; Cakmak, Sabit; Goldberg, Mark S.

2013-01-01

This study investigated associations between long-term exposure to ambient volatile organic compounds (VOCs) and mortality. 58,760 Toronto residents (≥35 years of age) were selected from tax filings and followed from 1982 to 2004. Death information was extracted using record linkage to national mortality data. Land-use regression surfaces for benzene, n-hexane, and total hydrocarbons were generated from sampling campaigns in 2002 and 2004 and assigned to residential addresses in 1982. Cox regression was used to estimate relationships between each VOC and non-accidental, cardiovascular, and cancer mortality. Positive associations were observed for each VOC. In multi-pollutant models the benzene and total hydrocarbon signals were strongest for cancer. The hazard ratio for cancer that corresponded to an increase in the interquartile range of benzene (0.13 μg/m 3 ) was 1.06 (95% CI = 1.02–1.11). Our findings suggest ambient concentrations of VOCs were associated with cancer mortality, and that these exposures did not confound our previously reported associations between NO 2 and cardiovascular mortality. -- Highlights: ► We studied associations between long-term exposure to volatile organic compounds and mortality. ► The study was a population-based cohort of Toronto adults followed for up to 22 years. ► We used land-use regression estimates of benzene, total hydrocarbons and n-hexane. ► Benzene and total hydrocarbons were positively associated with cancer mortality. ► VOCs did not confound associations between NO 2 and cardiovascular mortality. -- Long-term exposure to ambient benzene was associated with non-accidental and cancer causes of death, and did not attenuate associations between NO 2 and cardiovascular mortality

The Clinical Application of Raman Spectroscopy for Breast Cancer Detection

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Pin Gao

2017-01-01

Full Text Available Raman spectroscopy has been widely used as an important clinical tool for real-time in vivo cancer diagnosis. Raman information can be obtained from whole organisms and tissues, at the cellular level and at the biomolecular level. The aim of this paper is to review the newest developments of Raman spectroscopy in the field of breast cancer diagnosis and treatment. Raman spectroscopy can distinguish malignant tissues from noncancerous/normal tissues and can assess tumor margins or sentinel lymph nodes during an operation. At the cellular level, Raman spectra can be used to monitor the intracellular processes occurring in blood circulation. At the biomolecular level, surface-enhanced Raman spectroscopy techniques may help detect the biomarker on the tumor surface as well as evaluate the efficacy of anticancer drugs. Furthermore, Raman images reveal an inhomogeneous distribution of different compounds, especially proteins, lipids, microcalcifications, and their metabolic products, in cancerous breast tissues. Information about these compounds may further our understanding of the mechanisms of breast cancer.

A Flavone Constituent from Myoporum bontioides Induces M-Phase Cell Cycle Arrest of MCF-7 Breast Cancer Cells

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Jing-Ru Weng

2017-03-01

Full Text Available Abstract: Myoporum bontioides is a traditional medicinal plant in Asia with various biological activities, including anti-inflammatory and anti-bacterial characteristics. To identify the bioactive constituents from M. bontioides, a newly-identified flavone, 3,4′-dimethoxy-3′,5,7-trihydroxyflavone (compound 1, along with eight known compounds, were investigated in human MCF-7 breast cancer, SCC4 oral cancer, and THP-1 monocytic leukemia cells. Among these compounds, compound 1 exhibited the strongest antiproliferative activity with half-maximal inhibitory concentration (IC50 values ranging from 3.3 μM (MCF-7 to 8.6 μM (SCC4. Flow cytometric analysis indicated that compound 1 induced G2/M cell cycle arrest in MCF-7 cells. Mechanistic evidence suggests that the G2/M arrest could be attributable to compound 1’s modulatory effects on the phosphorylation and expression of numerous key signaling effectors, including cell division cycle 2 (CDC2, CDC25C, and p53. Notably, compound 1 downregulated the expression of histone deacetylase 2 (HDAC2 and HDAC4, leading to increased histone H3 acetylation and p21 upregulation. Together, these findings suggest the translational potential of compound 1 as a breast cancer treatment.

Chemistry-First Approach for Nomination of Personalized Treatment in Lung Cancer. | Office of Cancer Genomics

Science.gov (United States)

Diversity in the genetic lesions that cause cancer is extreme. In consequence, a pressing challenge is the development of drugs that target patient-specific disease mechanisms. To address this challenge, we employed a chemistry-first discovery paradigm for de novo identification of druggable targets linked to robust patient selection hypotheses. In particular, a 200,000 compound diversity-oriented chemical library was profiled across a heavily annotated test-bed of >100 cellular models representative of the diverse and characteristic somatic lesions for lung cancer.

Evaluation of in vitro anti-proliferative and immunomodulatory activities of compounds isolated from Curcuma longa

Science.gov (United States)

Yue, Grace G. L.; Chan, Ben C. L.; Hon, Po-Ming; Lee, Mavis Y. H.; Fung, Kwok-Pui; Leung, Ping-Chung; Lau, Clara B. S.

2010-01-01

The rhizome of Curcuma longa (CL) has been commonly used in Asia as a potential candidate for the treatment of different diseases, including inflammatory disorders and cancers. The present study evaluated the anti-proliferative activities of the isolated compounds (3 curcuminoids and 2 turmerones) from CL, using human cancer cell lines HepG2, MCF-7 and MDA-MB-231. The immunomodulatory activities of turmerones (α and aromatic) isolated from CL were also examined using human peripheral blood mononuclear cells (PBMC). Our results showed that the curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) and α-turmerone significantly inhibited proliferation of cancer cells in dose-dependent manner. The IC50 values of these compounds in cancer cells ranged from 11.0–41.8 μg/ml. Alpha-turmerone induced MDA-MB-231 cells to undergo apoptosis, which was confirmed by annexin-V & propidium iodide staining, and DNA fragmentation assay. The caspase cascade was activated as shown by a significant decrease of procaspases-3, -8 and -9 in α-turmerone treated cells. Both α-turmerone and aromatic-turmerone showed stimulatory effects on PBMC proliferation and cytokine production. The anti-proliferative effect of α-turmerone and immunomodulatory activities of ar-turmerone were shown for the first time. The findings revealed the potential use of CL crude extract (containing curcuminoids and volatile oil including turmerones) as chemopreventive agent. PMID:20438793

Impact of Saccharomyces cerevisiae Strains on Health-Promoting Compounds in Wine

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Simona Guerrini

2018-04-01

Full Text Available Moderate wine consumption is associated with human health benefits (reduction of cardiovascular risk and neurodegenerative diseases, decrease of onset of certain cancers attributed to a series of bioactive compounds, mainly polyphenols, with antioxidant power capable of counteracting the negative action of free radicals. Polyphenols are naturally present in the grapes, but an additional amount originates during winemaking. The aim of this work was to assess the ability of four commercial and two indigenous Saccharomyces cerevisiae strains to produce bioactive compounds (tyrosol, hydroxytyrosol, tryptophol, melatonin and glutathione during alcoholic fermentation. In order to exclude the fraction of antioxidant compounds naturally occurring in grapes, the strains were inoculated in a synthetic must. At the end of fermentation the bioactive compounds were analysed by High-Performance Liquid Chromatography, while antioxidant activity was measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH assay. Moreover, freeze-dried samples, originating from the experimental wines, were used to perform ex-vivo assays on cultured cells (RAW 264.7 murine macrophages with the aim to evaluate their antioxidant and anti-inflammatory activities. The results indicated that the production of the considered bioactive compounds is a strain-specific property; therefore, the different yeast strains utilized during fermentation have different capabilities to modify the antioxidant and anti-inflammatory properties of the wine.

Amplexicaule A exerts anti-tumor effects by inducing apoptosis in human breast cancer

Science.gov (United States)

Shu, Guangwen; Wan, Dingrong; He, Feng; Loaec, Morgann; Ding, Yali; Li, Jun; Dovat, Sinisa; Yang, Gaungzhong; Song, Chunhua

2016-01-01

Chemotherapy is the main treatment for patients with breast cancer metastases, but natural alternatives have been receiving attention for their potential as novel anti-tumor reagents. Amplexicaule A (APA) is a flavonoid glucoside isolated from rhizomes of Polygonum amplexicaule D. Don var. sinense Forb (PADF). We found that APA has anti-tumor effects in a breast cancer xenograft mouse model and induces apoptosis in breast cancer cell lines. APA increased levels of cleaved caspase-3,-8,-9 and PARP, which resulted from suppression of MCL-1 and BCL-2 expression in the cells. APA also inactivated the Akt/mTOR pathway in breast cancer cells. Thus, APA exerts a strong anti-tumor effect on breast cancer cells, most likely through induction of apoptosis. Our study is the first to identify this novel anti-tumor compound and provides a new strategy for isolation and separation of single compounds from herbs. PMID:26943775

Mutagenic and antimutagenic activity of food compounds : Application of a dynamic in vitro gastrointestinal model

NARCIS (Netherlands)

Krul, Cyrille Anna Maria

2001-01-01

Exposure of humans to potential mutagenic and carcinogenic food compounds through the diet is unavoidable. On the other hand, there is epidemiological evidence for antimutagenic and anticarcinogenic properties of food as well (such as vegetables and fruit). The assessment of carcinogenic and cancer

24-Methylenecycloartanyl ferulate, a major compound of γ-oryzanol, promotes parvin-beta expression through an interaction with peroxisome proliferator-activated receptor-gamma 2 in human breast cancer cells.

Science.gov (United States)

Kim, Heon Woong; Lim, Eun Joung; Jang, Hwan Hee; Cui, XueLei; Kang, Da Rae; Lee, Sung Hyen; Kim, Haeng Ran; Choe, Jeong Sook; Yang, Young Mok; Kim, Jung Bong; Park, Jong Hwan

2015-12-25

Parvin-β is an adaptor protein that binds to integrin-linked kinase (ILK) and is significantly downregulated in breast tumors and breast cancer cell lines. We treated the breast cancer cell line MCF7 with 24-methylenecycloartanyl ferulate (24-MCF), a γ-oryzanol compound. We observed upregulation of parvin-β (GenBank Accession No. AF237769) and peroxisome proliferator-activated receptor (PPAR)-γ2 (GenBank Accession No. NM_015869). Among γ-oryzanol compounds, only treatment with 24-MCF led to the formation of reverse transcription-PCR products of parvin-β (650 and 500 bp) and PPAR-γ2 (580 bp) in MCF7 cells, but not in T47D, SK-BR-3, or MDA-MB-231 cells. 24-MCF treatment increased the mRNA and protein levels of parvin-β in MCF7 cells in a dose-dependent manner. We hypothesized that there is a correlation between parvin-β expression and induction of PPAR-γ2. This hypothesis was investigated by using a promoter-reporter assay, chromatin immunoprecipitation, and an electrophoretic mobility shift assay. 24-MCF treatment induced binding of PPAR-γ2 to a peroxisome proliferator response element-like cis-element (ACTAGGACAAAGGACA) in the parvin-β promoter in MCF7 cells in a dose-dependent manner. 24-MCF treatment significantly decreased anchorage-independent growth and inhibited cell movement in comparison to control treatment with dimethyl sulfoxide. 24-MCF treatment reduced the levels of GTP-bound Rac1 and Cdc42. Evaluation of Akt1 inhibition by 24-MCF revealed that the half maximal effective concentration was 33.3 μM. Docking evaluations revealed that 24-MCF binds to the ATP-binding site of Akt1(PDB ID: 3OCB) and the compound binding energy is -8.870 kcal/mol. Taken together, our results indicate that 24-MCF treatment increases parvin-β expression, which may inhibit ILK downstream signaling. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Targeted Therapies in Epithelial Ovarian Cancer

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Jurjees Hasan

2010-02-01

Full Text Available Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer.

Targeted Therapies in Epithelial Ovarian Cancer

Energy Technology Data Exchange (ETDEWEB)

Dean, Emma; El-Helw, Loaie; Hasan, Jurjees, E-mail: jurjees.hasan@christie.nhs.uk [Christie Hospital NHS Foundation Trust / Wilmslow Road, Manchester, M20 4BX (United Kingdom)

2010-02-23

Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer.

Identification of cancer cytotoxic modulators of PDE3A by predictive chemogenomics

Science.gov (United States)

de Waal, Luc; Lewis, Timothy A.; Rees, Matthew G.; Tsherniak, Aviad; Wu, Xiaoyun; Choi, Peter S.; Gechijian, Lara; Hartigan, Christina; Faloon, Patrick W.; Hickey, Mark J.; Tolliday, Nicola; Carr, Steven A.; Clemons, Paul A.; Munoz, Benito; Wagner, Bridget K.; Shamji, Alykhan F.; Koehler, Angela N.; Schenone, Monica; Burgin, Alex B.; Schreiber, Stuart L.; Greulich, Heidi; Meyerson, Matthew

2015-01-01

High cancer death rates indicate the need for new anti-cancer therapeutic agents. Approaches to discover new cancer drugs include target-based drug discovery and phenotypic screening. Here, we identified phosphodiesterase 3A modulators as cell-selective cancer cytotoxic compounds by phenotypic compound library screening and target deconvolution by predictive chemogenomics. We found that sensitivity to 6-(4-(diethylamino)-3-nitrophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one, or DNMDP, across 766 cancer cell lines correlates with expression of the phosphodiesterase 3A gene, PDE3A. Like DNMDP, a subset of known PDE3A inhibitors kill selected cancer cells while others do not. Furthermore, PDE3A depletion leads to DNMDP resistance. We demonstrated that DNMDP binding to PDE3A promotes an interaction between PDE3A and Schlafen 12 (SLFN12), suggesting a neomorphic activity. Co-expression of SLFN12 with PDE3A correlates with DNMDP sensitivity, while depletion of SLFN12 results in decreased DNMDP sensitivity. Our results implicate PDE3A modulators as candidate cancer therapeutic agents and demonstrate the power of predictive chemogenomics in small-molecule discovery. PMID:26656089

Cancer Chemoprevention by Carotenoids

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Takuji Tanaka

2012-03-01

Full Text Available Carotenoids are natural fat-soluble pigments that provide bright coloration to plants and animals. Dietary intake of carotenoids is inversely associated with the risk of a variety of cancers in different tissues. Preclinical studies have shown that some carotenoids have potent antitumor effects both in vitro and in vivo, suggesting potential preventive and/or therapeutic roles for the compounds. Since chemoprevention is one of the most important strategies in the control of cancer development, molecular mechanism-based cancer chemoprevention using carotenoids seems to be an attractive approach. Various carotenoids, such as β-carotene, a-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, fucoxanthin, canthaxanthin and astaxanthin, have been proven to have anti-carcinogenic activity in several tissues, although high doses of β-carotene failed to exhibit chemopreventive activity in clinical trials. In this review, cancer prevention using carotenoids are reviewed and the possible mechanisms of action are described.

Review of carcinogenicity of hexavalent chrome and proposal of revising approval standards for an occupational cancers in Korea.

Science.gov (United States)

Kim, Jungwon; Seo, Sangyun; Kim, Yangho; Kim, Dae Hwan

2018-01-01

to chromium (VI) or compounds thereof (exposure for two years or longer), or nickel compounds" should be changed to "Lung cancer caused by exposure to chromium (VI) or compounds thereof, and lung cancer or nasal and paranasal sinus cancer caused by exposure to nickel compounds".

Antiproliferative Compounds of Cyphostemma greveana from a Madagascar Dry Forest[1

Science.gov (United States)

Cao, Shugeng; Hou, Yanpeng; Brodie, Peggy; Miller, James S.; Randrianaivo, Richard; Rakotobe, Etienne; Rasamison, Vincent E.

2011-01-01

Bioassay-guided fractionation of the EtOH extracts obtained from a plant identified as Cyphostemma greveana Desc. (Vitaceae) led to the identification of one macrolide, lasiodiplodin (1), three sesquiterpenoids, 12-hydroxy-15-oxo-selina-4,1l-diene (2), 1β,6α-dihydroxyeudesm-4(15)-ene (3), and (7R*)-opposit-4(15)-ene-1β,7-diol (5), and the new diterpenoid, 16,18-dihydroxykolavenic acid lactone (4). All the isolates were tested against the A2780 human ovarian cancer cell line, and compound 4 and a fraction containing 5 as the major constituent showed antiproliferative activities with IC50 values of 0.44 μM (0.14 μg/mL) and 0.045 μg/mL, respectively. A semisynthesis of compound 5 was carried out, but the pure synthetic compound was inactive, indicating that the activity of the fraction containing it must be due to a very minor and as yet unidentified substance. PMID:21480509

Investigation of the selenium metabolism in cancer cell lines

DEFF Research Database (Denmark)

Lunøe, Kristoffer; Gabel-Jensen, Charlotte; Stürup, Stefan

2011-01-01

The aim of this work was to compare different selenium species for their ability to induce cell death in different cancer cell lines, while investigating the underlying chemistry by speciation analysis. A prostate cancer cell line (PC-3), a colon cancer cell line (HT-29) and a leukaemia cell line...... (Jurkat E6-1) were incubated with five selenium compounds representing inorganic as well as organic Se compounds in different oxidation states. Selenomethionine (SeMet), Se-methylselenocysteine (MeSeCys), methylseleninic acid (MeSeA), selenite and selenate in the concentration range 5-100 mu M were...... incubated with cells for 24 h and the induction of cell death was measured using flow cytometry. The amounts of total selenium in cell medium, cell lysate and the insoluble fractions was determined by ICP-MS. Speciation analysis of cellular fractions was performed by reversed phase, anion exchange and size...

Checkpoint inhibitors in breast cancer

DEFF Research Database (Denmark)

Polk, Anne; Svane, Inge-Marie; Andersson, Michael

2018-01-01

INTRODUCTION: An increasing number of compounds directed against immune checkpoints are currently under clinical development. In this review we summarize current research in breast cancer. MATERIAL AND METHODS: A computer-based literature search was carried out using PubMed and EMBASE; data...... reported at international meetings and clinicaltrials.gov were included as well. RESULTS: The obtained overall response rate of PD-1/PD-L1 monotherapy varied from 5 to 30% in heavily pretreated triple negative breast cancer (TNBC). The median duration of progression free survival and overall survival were...... and induce long standing anti-tumor immunity in a subgroup of breast cancer patients. However, the identification of predictive biomarkers is crucial for further development of this treatment modality....

Garlic-derived compound S-allylmercaptocysteine (SAMC) is active against anaplastic thyroid cancer cell line 8305C (HPACC).

Science.gov (United States)

Liu, Yuexin; Yan, Jinyin; Han, Xiaochen; Hu, Wanning

2015-01-01

Epidemiological and experimental carcinogenesis studies provide evidence that components of garlic have anticancer activity. In this study, the apoptotic effects of Garlic-derived compound S-allylmercaptocysteine (SAMC) were investigated in 8305C human anaplastic thyroid carcinoma cells. The cell line 8305C (HPACC) were treated with SAMC and the MTT assay, flow cytometry (FCM), electron microscope method were used to test cell cycle, inhibitory rate and morphologic changes respectively. HPACC-8305C cells were suppressed after exposure to SAMC of 0.02 mg/ml, 0.06 mg/ml, and 0.1 mg/ml for 48 h. Compared with the control, the difference was significant (P< 0.05). SAMC could induce apoptosis of the cells in a dose-dependent and non-linear manner and increase the proportion of cells in the G2/M phase. Compared with the control, the difference was significant in terms of the percentage of cells in the G2/M phase (P< 0.05). After exposure to SAMC at 0.02 mg/ml for 24 hours, HPACC-8305C cells showed typical morphologic change. SAMC inhibits the growth of HPACC-8305C cells by induction of apoptotic cell death and inhibit telomerase activity, which appears to account for its anti-cancer activity.

Risk of breast cancer among enlisted Army women occupationally exposed to volatile organic compounds.

Science.gov (United States)

Rennix, Christopher P; Quinn, Margaret M; Amoroso, Paul J; Eisen, Ellen A; Wegman, David H

2005-09-01

The military presents a unique opportunity to study the incidence of disease in a population with complete knowledge of person-time and occupation. Women in the Army are employed more frequently in non-traditional, industrial jobs such as auto mechanic and motor transport operators than in the general US population, increasing the probability of exposure to industrial chemicals. A cohort to investigate the risk of breast cancer among active duty Army women occupationally exposed to volatile organic chemicals (VOCs) was constructed. Age-adjusted incidence rates for breast cancer were calculated for more than 270,000 enlisted women who served between 1980-1996. Twenty-one VOCs, described in previously published literature as having a potential risk of breast cancer, were identified in an Army industrial hygiene survey database. Job title histories were linked to workplace chemical evaluations conducted by Army industrial hygienists, which included a subjective exposure potential rating (high, medium, low, and none) for each VOC. Poisson regression analysis was used to evaluate the association between the exposure rating by job title and breast cancer. The incidence of breast cancer in the cohort was significantly elevated in women younger than 35 years of age, especially among black women, when compared to the age-specific rates in the general population. Women who worked in occupations with a moderate to high exposure potential to at least one VOC had a 48% increased risk (P women with low to no exposure potential. This study provides preliminary evidence that exposure to one or more of the study VOCs is associated with an increased risk of breast cancer. Further substance-specific, quantitative analyses are warranted.

Marine Fungi: A Source of Potential Anticancer Compounds

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Sunil K. Deshmukh

2018-01-01

Full Text Available Metabolites from marine fungi have hogged the limelight in drug discovery because of their promise as therapeutic agents. A number of metabolites related to marine fungi have been discovered from various sources which are known to possess a range of activities as antibacterial, antiviral and anticancer agents. Although, over a thousand marine fungi based metabolites have already been reported, none of them have reached the market yet which could partly be related to non-comprehensive screening approaches and lack of sustained lead optimization. The origin of these marine fungal metabolites is varied as their habitats have been reported from various sources such as sponge, algae, mangrove derived fungi, and fungi from bottom sediments. The importance of these natural compounds is based on their cytotoxicity and related activities that emanate from the diversity in their chemical structures and functional groups present on them. This review covers the majority of anticancer compounds isolated from marine fungi during 2012–2016 against specific cancer cell lines.

Phenolic Compounds of Cereals and Their Antioxidant Capacity.

Science.gov (United States)

Van Hung, Pham

2016-01-01

Phenolic compounds play an important role in health benefits because of their highly antioxidant capacity. In this review, total phenolic contents (TPCs), phenolic acid profile and antioxidant capacity of the extracted from wheat, corn, rice, barley, sorghum, rye, oat, and millet, which have been recently reported, are summarized. The review shows clearly that cereals contain a number of phytochemicals including phenolics, flavonoids, anthocyanins, etc. The phytochemicals of cereals significantly exhibit antioxidant activity as measured by trolox equivalent antioxidant capacity (TEAC), 2,2-diphenyl-1-picrylhydrazyl radical scavenging, reducing power, oxygen radical absorbance capacity (ORAC), inhibition of oxidation of human low-density lipoprotein (LDL) cholesterol and DNA, Rancimat, inhibition of photochemilumenescence (PCL), and iron(II) chelation activity. Thus, the consumption of whole grains is considered to have significantly health benefits in prevention from chronic diseases such as cardiovascular disease, diabetes, and cancer because of the contribution of phenolic compounds existed. In addition, the extracts from cereal brans are considered to be used as a source of natural antioxidants.

Heterocyclic organobismuth (III) compounds containing an eight-membered ring: Inhibitory effects on cell cycle progression.

Science.gov (United States)

Iuchi, Katsuya; Yagura, Tatsuo

2018-03-21

We previously showed that heterocyclic organobismuth compounds have excellent antimicrobial and antitumor potential. These compounds structurally consist of either six- or eight-membered rings. Previous research has shown that bi-chlorodibenzo[c,f][1,5]thiabismocine (Compound 3), an eight-membered ring, induced G 2 /M arrest via inhibition of tubulin polymerization in HeLa cells. Additionally, N-tert-butyl-bi-chlorodi-benzo[c,f][1,5]azabismocine (Compound 1), another eight-membered ring, exhibited higher cytotoxicity than Compound 3 against several cancer cell lines, including HeLa and K562. Finally, bi-chlorophenothiabismin-S,S-dioxide (Compound 5), a six-membered ring, exhibited lower antitumor activity than eight-membered ring compounds. In this study, we investigated the antimitotic activity of Compounds 1 and 5 in HeLa cells. At low concentrations, (0.1 and 0.25 μM), Compound 1 inhibited cell growth and arrested the cell cycle in mitosis. However, 0.5 μM Compound 1 exhibited no antimitotic activity. Conversely, Compound 5 weakly inhibited cell growth and did not markedly arrest the cell cycle. Flow cytometry showed that Compound 1 arrested the cell cycle at G 2 /M, resulting in apoptosis. Compound 1 inhibited tubulin polymerization as revealed by a cell-free assay, and both Compounds 1 and 3 inhibited microtubule spindle formation and chromosome alignment during prometaphase. These results suggest that eight-membered ring-containing organobismuth compounds can induce mitotic arrest by perturbing spindle dynamics. Copyright © 2018. Published by Elsevier Ltd.

Antiproliferative compounds of Cyphostemma greveana from a Madagascar dry forest.

Science.gov (United States)

Cao, Shugeng; Hou, Yanpeng; Brodie, Peggy; Miller, James S; Randrianaivo, Richard; Rakotobe, Etienne; Rasamison, Vincent E; Kingston, David G I

2011-04-01

Bioassay-guided fractionation of the EtOH extracts obtained from a plant identified as Cyphostemma greveana Desc. (Vitaceae) led to the identification of one macrolide, lasiodiplodin (1), three sesquiterpenoids, 12-hydroxy-15-oxoselina-4,11-diene (2), 1β,6α-dihydroxyeudesm-4(15)-ene (3), and (7R*)-opposit-4(15)-ene-1β,7-diol (5), and a new diterpenoid, 16,18-dihydroxykolavenic acid lactone (4). All the isolates were tested against the A2780 human ovarian cancer cell line, and compound 4 and a fraction containing 5 as the major constituent showed antiproliferative activities with IC(50) values of 0.44 μM (0.14 μg/ml) and 0.045 μg/ml, respectively. A partial synthesis of compound 5 was carried out, but the pure synthetic compound was inactive, indicating that the activity of the fraction containing it must be due to a very minor and as yet unidentified substance. Copyright © 2011 Verlag Helvetica Chimica Acta AG, Zürich.

Synthesis, Characterization, and Anti-Cancer Activity of Some New N′-(2-Oxoindolin-3-ylidene-2-propylpentane hydrazide-hydrazones Derivatives

Directory of Open Access Journals (Sweden)

Ayman El-Faham

2015-08-01

Full Text Available Eight novel N′-(2-oxoindolin-3-ylidene-2-propylpentane hydrazide-hydrazone derivatives 4a–h were synthesized and fully characterized by IR, NMR (1H-NMR and 13C-NMR, elemental analysis, and X-ray crystallography. The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against two different human tumour cell lines including human liver (HepG2 and leukaemia (Jurkat, as well as in normal cell lines derived from human embryonic kidney (HEK293 using MTT assay. The compounds 3e, 3f, 4a, 4c, and 4e revealed promising anti-cancer activities in tested human tumour cells lines (IC50 values between 3 and 7 μM as compared to the known anti-cancer drug 5-Fluorouracil (IC50 32–50 μM. Among the tested compounds, 4a showed specificity against leukaemia (Jurkat cells, with an IC50 value of 3.14 μM, but this compound was inactive in liver cancer and normal cell lines.

Synthesis of some new heterocyclic compounds bearing a sulfonamide moiety and studying their combined anticancer effect with γ-radiation

International Nuclear Information System (INIS)

El-Hossary, E.M.M.

2010-01-01

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

Esophageal perforation

Science.gov (United States)

... esophagus into the space around the lungs. Collapsed lung. X-rays taken after you drink a non-harmful dye can help pinpoint the location of the perforation. You may also have chest CT scan look for an abscess in the chest or esophageal cancer.

Exploring the molecular targets of dietary flavonoid fisetin in cancer.

Science.gov (United States)

Syed, Deeba N; Adhami, Vaqar Mustafa; Khan, Naghma; Khan, Mohammad Imran; Mukhtar, Hasan

2016-10-01

The last few decades have seen a resurgence of interest among the scientific community in exploring the efficacy of natural compounds against various human cancers. Compounds of plant origin belonging to different groups such as alkaloids, flavonoids and polyphenols evaluated for their cancer preventive effects have yielded promising data, thereby offering a potential therapeutic alternative against this deadly disease. The flavonol fisetin (3,3',4',7-tetrahydroxyflavone), present in fruits and vegetables such as strawberries, apple, cucumber, persimmon, grape and onion, was shown to possess anti-microbial, anti-inflammatory, anti-oxidant and more significantly anti-carcinogenic activity when assessed in diverse cell culture and animal model systems. The purpose of this review is to update and discuss key findings obtained till date from in vitro and in vivo studies on fisetin, with special focus on its anti-cancer role. The molecular mechanism(s) described in the observed growth inhibitory effects of fisetin in different cancer cell types is also summarized. Moreover, an attempt is made to delineate the direction of future studies that could lead to the development of fisetin as a potent chemopreventive/chemotherapeutic agent against cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bioactive compounds in bee propolis for drug discovery

Science.gov (United States)

Kumazawa, Shigenori

2018-02-01

Propolis is a natural resinous product collected by honeybees. It has been used in folk medicine since ancient times because of its numerous biological properties such as antioxidant, antimicrobial, anti-cancer, and anti-inflammatory activities. Studies of the chemical composition of propolis have demonstrated that its compositional variability depends on the source plant. We have studied the chemistry and biological activities of various types of propolis from Apis mellifera. The studies of propolis collected in Brazil, Japan, Korea, the Solomon Island and Senegal are summarized. Brazilian green propolis contained high levels of artepillin C (3,5-diprenyl-4-hydroxycinnamic acid), which has a potent apoptosis-inducing agent as well as an angiogenesis inhibitor. The several phenolic compounds with potent antibacterial activity in Brazilian red propolis were found. The propolis from Okinawa, Japan, contained some prenylflavonoids with antioxidant and antimicrobial activities. The propolis from the Solomon Islands and Hawaii have the same compounds as Okinawan propolis. The propolis from Jeju Island, Korea had the promotion effect on nerve growth factor (NGF) secretion in human glioblastoma T98G cells. The compounds isolated from Senegalese propolis showed high anti-inflammatory activity due to their inhibition of the liposaccharide (LPS)-induced expression of inducible NO synthase (iNOS).

Potential New Pharmacological Agents Derived From Medicinal Plants for the Treatment of Pancreatic Cancer.

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Azimi, Haniye; Khakshur, Ali Asghar; Abdollahi, Mohammad; Rahimi, Roja

2015-01-01

In the present article, we reviewed plants and phytochemical compounds demonstrating beneficial effects in pancreatic cancer to find new sources of pharmaceutical agents. For this purpose, Scopus, PubMed, Web of Science, and Google scholar were searched for plants or herbal components with beneficial effects in the treatment of pancreatic cancer. Data were collected up to January 2013. The search terms were "plant," "herb," "herbal therapy," or "phytotherapy" and "pancreatic cancer" or "pancreas." All of the human in vivo and in vitro studies were included. According to studies, among diverse plants and phytochemicals, 12 compounds including apigenin, genistein, quercetin, resveratrol, epigallocatechin gallate, benzyl isothiocyanate, sulforaphane, curcumin, thymoquinone, dihydroartemisinin, cucurbitacin B, and perillyl alcohol have beneficial action against pancreatic cancer cells through 4 or more mechanisms. Applying their plausible synergistic effects can be an imperative approach for finding new efficient pharmacological agents in the treatment of pancreatic cancer.

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

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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.

Porritoxins, metabolites of Alternaria porri, as anti-tumor-promoting active compounds.

Science.gov (United States)

Horiuchi, Masayuki; Tokuda, Harukuni; Ohnishi, Keiichiro; Yamashita, Masakazu; Nishino, Hoyoku; Maoka, Takashi

2006-02-01

To search for possible cancer chemopreventive agents from natural sources, we performed primary screening of metabolites of Alternaria porri by examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. The ethyl acetate extract of A. porri showed the inhibitory effect on EBV-EA activation. Three porritoxins (1-3) were obtained as inhibitory active compounds for EBV-EA from ethyl acetate extract. 6-(3',3'-Dimethylallyloxy)-4-methoxy-5-methylphthalide (2) showed the strongest activity among them. Inhibitory effect of porritoxin (1) and (2) was superior to that of beta-carotene, a well-known anti-tumor promoter. Furthermore, the structure-activity correlation of porritoxins and their related compounds were discussed.

Melatonin as a multifunctional anti-cancer molecule: Implications in gastric cancer.

Science.gov (United States)

Asghari, Mohammad Hossein; Moloudizargari, Milad; Ghobadi, Emad; Fallah, Marjan; Abdollahi, Mohammad

2017-09-15

Gastric cancer (GC) is a predominant malignancy with a high mortality rate affecting a large population worldwide. The etiology of GC is multifactorial spanning from various genetic determinants to different environmental causes. Current tretaments of GC are not efficient enough and require improvements to minimize the adverse effects. Melatonin, a naturally occurring compound with known potent inhibitory effects on cancer cells is one of the major candidates which can be recruited herein. Here we reviewed the articles conducted on the therapeutic effects of melatonin in gastric cancer in various models. The results are classified according to different aspects of cancer pathogenesis and the molecular mechanisms by which melatonin exerts its effects. Melatonin could be used to combat GC exploiting its effects on multiple aspects of its pathogenesis, including formation of cancer cells, tumor growth and angiogenesis, differentiation and metastasis as well as enhancing the anti-tumor immunity. Melatonin is a pleiotropic anti-cancer molecule that affects malignant cells via multiple mechanisms. It has been shown to benefit cancer patients indirectly by reducing side effects of current therapies which have been discussed in this review. This field of research is still underdeveloped and may serve as an interesting subject for further studies aiming at the molecular mechanisms of melatonin and novel treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

Association between red meat consumption and colon cancer: A systematic review of experimental results.

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Turner, Nancy D; Lloyd, Shannon K

2017-04-01

A role for red and processed meat in the development of colorectal cancer has been proposed based largely on evidence from observational studies in humans, especially in those populations consuming a westernized diet. Determination of causation specifically by red or processed meat is contingent upon identification of plausible mechanisms that lead to colorectal cancer. We conducted a systematic review of the available evidence to determine the availability of plausible mechanistic data linking red and processed meat consumption to colorectal cancer risk. Forty studies using animal models or cell cultures met specified inclusion criteria, most of which were designed to examine the role of heme iron or heterocyclic amines in relation to colon carcinogenesis. Most studies used levels of meat or meat components well in excess of those found in human diets. Although many of the experiments used semi-purified diets designed to mimic the nutrient loads in current westernized diets, most did not include potential biologically active protective compounds present in whole foods. Because of these limitations in the existing literature, there is currently insufficient evidence to confirm a mechanistic link between the intake of red meat as part of a healthy dietary pattern and colorectal cancer risk. Impact statement Current recommendations to reduce colon cancer include the reduction or elimination of red or processed meats. These recommendations are based on data from epidemiological studies conducted among cultures where meat consumption is elevated and consumption of fruits, vegetables, and whole grains are reduced. This review evaluated experimental data exploring the putative mechanisms whereby red or processed meats may contribute to colon cancer. Most studies used levels of meat or meat-derived compounds that were in excess of those in human diets, even in cultures where meat intake is elevated. Experiments where protective dietary compounds were used to mitigate the

Isotopically modified compounds

International Nuclear Information System (INIS)

Kuruc, J.

2009-01-01

In this chapter the nomenclature of isotopically modified compounds in Slovak language is described. This chapter consists of following parts: (1) Isotopically substituted compounds; (2) Specifically isotopically labelled compounds; (3) Selectively isotopically labelled compounds; (4) Non-selectively isotopically labelled compounds; (5) Isotopically deficient compounds.

Eugenol and its synthetic analogues inhibit cell growth of human cancer cells (Part I)

International Nuclear Information System (INIS)

Carrasco A, H.; Cardona, W.; Espinoza C, L.; Gallardo, C.; Catalan M, K.; Cardile, V.; Lombardo, L.; Cuellar F, M.; Russo, A.

2008-01-01

Eugenol (4-allyl-2-methoxyphenol) (1) has been reported to possess antioxidant and anticancer properties. In an attempt to enhance intrinsic activity of this natural compound, some derivatives were synthesized. Eugenol was extracted from cloves oil and further, the eugenol analogues (2-6) were obtained through acetylation and nitration reactions. Eugenol (1) and its analogues (2-6) were examined by in vitro model of cancer using two human cancer cell lines: DU-145 (androgeninsensitive prostate cancer cells) and KB (oral squamous carcinoma cells). Cell viability, by tetrazolium salts assay, was measured. Lactic dehydrogenase (LDH) release was also investigated to evaluate the presence of cell toxicity as a result of cell disruption, subsequent to membrane rupture. In the examined cancer cells, all compounds showed cell-growth inhibition activity. The obtained results demonstrate that the compounds 5-allyl-3-nitrobenzene-1,2-diol (3) and 4-allyl- 2-methoxy-5-nitrophenyl acetate (5) were significantly (p 50 values in DU-145 cells of 19.02 x 10 -6 and 21.5 x 10 -6 mol L -1 , respectively, and in KB cells of 18.11 x 10 -6 and 21.26 x 10 -6 mol L -1 , respectively, suggesting that the presence of nitro and hydroxyl groups could be important in the activity of these compounds. In addition, our results seem to indicate that apoptotic cell demise appears to be induced in KB and DU-145 cells. In fact, in our experimental conditions, no statistically significant increase in LDH release was observed in cancer cells treated with eugenol and its analogues. (author)

Identification of a novel compound (β-sesquiphellandrene) from turmeric (Curcuma longa) with anticancer potential: comparison with curcumin.

Science.gov (United States)

Tyagi, Amit Kumar; Prasad, Sahdeo; Yuan, Wei; Li, Shiyou; Aggarwal, Bharat B

2015-12-01

Considering that as many as 80% of the anticancer drugs have their roots in natural products derived from traditional medicine, we examined compounds other than curcumin from turmeric (Curcuma longa) that could exhibit anticancer potential. Present study describes the isolation and characterization of another turmeric-derived compound, β-sesquiphellandrene (SQP) that exhibits anticancer potential comparable to that of curcumin. We isolated several compounds from turmeric, including SQP, α-curcumene, ar-turmerone, α-turmerone, β-turmerone, and γ-turmerone, only SQP was found to have antiproliferative effects comparable to those of curcumin in human leukemia, multiple myeloma, and colorectal cancer cells. While lack of the NF-κB-p65 protein had no effect on the activity of SQP, lung cancer cells that expressed p53 were more susceptible to the cytotoxic effect of SQP than were cells that lacked p53 expression. SQP was also found to be highly effective in suppressing cancer cell colony formation and inducing apoptosis, as shown by assays of intracellular esterase activity, plasma membrane integrity, and cell-cycle phase. SQP was found to induce cytochrome c release and activate caspases that lead to poly ADP ribose polymerase cleavage. SQP exposure was associated with downregulation of cell survival proteins such cFLIP, Bcl-xL, Bcl-2, c-IAP1, and survivin. Furthermore, SQP was found to be synergistic with the chemotherapeutic agents velcade, thalidomide and capecitabine. Overall, our results indicate that SQP has anticancer potential comparable to that of curcumin.

Design, Synthesis and Evaluation of N13-Substituted Evodiamine Derivatives against Human Cancer Cell Lines

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Senchuan Song

2013-12-01

Full Text Available Attempting to improve the anticancer activity and solubility of evodiamine in simulated gastric fluid (SGF and simulated intestinal fluid (SIF solutions, thirty-eight N13-substituted evodiamine derivatives were designed, synthesized and tested for antitumor activities against six kinds of human cancer cell lines, namely prostate cancer (DU-145 and PC-3, lung cancer (H460, breast cancer (MCF-7, colon cancer (HCT-5 and glioblastoma (SF-268. The solubility of these compounds in SGF and SIF solutions was evaluated, and apoptosis induced by 2-2, 2-3, 2-16 and 3-2 was determined. The results showed: (1 among all compounds examined, 2-16 showed the highest antitumor activity and a broader spectrum of activity, with IC50 values ranging from 1–2 µM; (2 their solubility was obviously improved; (3 2-3, 2-16 and 3-2 had a significant impact inducing apoptosis in some cancer cell lines. The preliminary structure-activity relationships of these derivatives were discussed.

Dietary factors and epigenetic regulation for prostate cancer prevention.

Science.gov (United States)

Ho, Emily; Beaver, Laura M; Williams, David E; Dashwood, Roderick H

2011-11-01

The role of epigenetic alterations in various human chronic diseases has gained increasing attention and has resulted in a paradigm shift in our understanding of disease susceptibility. In the field of cancer research, e.g., genetic abnormalities/mutations historically were viewed as primary underlying causes; however, epigenetic mechanisms that alter gene expression without affecting DNA sequence are now recognized as being of equal or greater importance for oncogenesis. Methylation of DNA, modification of histones, and interfering microRNA (miRNA) collectively represent a cadre of epigenetic elements dysregulated in cancer. Targeting the epigenome with compounds that modulate DNA methylation, histone marks, and miRNA profiles represents an evolving strategy for cancer chemoprevention, and these approaches are starting to show promise in human clinical trials. Essential micronutrients such as folate, vitamin B-12, selenium, and zinc as well as the dietary phytochemicals sulforaphane, tea polyphenols, curcumin, and allyl sulfur compounds are among a growing list of agents that affect epigenetic events as novel mechanisms of chemoprevention. To illustrate these concepts, the current review highlights the interactions among nutrients, epigenetics, and prostate cancer susceptibility. In particular, we focus on epigenetic dysregulation and the impact of specific nutrients and food components on DNA methylation and histone modifications that can alter gene expression and influence prostate cancer progression.

Podoplanin - an emerging cancer biomarker and therapeutic target.

Science.gov (United States)

Krishnan, Harini; Rayes, Julie; Miyashita, Tomoyuki; Ishii, Genichiro; Retzbach, Edward P; Sheehan, Stephanie A; Takemoto, Ai; Chang, Yao-Wen; Yoneda, Kazue; Asai, Jun; Jensen, Lasse; Chalise, Lushun; Natsume, Atsushi; Goldberg, Gary S

2018-03-25

Podoplanin (PDPN) is a transmembrane receptor glycoprotein that is upregulated on transformed cells, cancer associated fibroblasts (CAFs), and inflammatory macrophages that contribute to cancer progression. In particular, PDPN increases tumor cell clonal capacity, epithelial mesenchymal transition (EMT), migration, invasion, metastasis, and inflammation. Antibodies, CAR-T cells, biologics, and synthetic compounds that target PDPN can inhibit cancer progression and septic inflammation in preclinical models. This review describes recent advances in how PDPN may be used as a biomarker and therapeutic target for many types of cancer including glioma, squamous cell carcinoma, mesothelioma, and melanoma. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Multivalent Peptidomimetic Conjugates as Inhibitors of Androgen Receptor Function in Therapy-Resistant Prostate Cancer

Science.gov (United States)

2017-10-01

androgen), with more or less intervening monomers in between the ethisterone ligands diminishing compound activities. We are now creating a set of MPC6...disseminated to communities of interest ? We published a paper on this topic in Cancer Research Cancer Res. 2016 Sep 1;76(17):5124- 32. doi: 10.1158/0008...We will test all of the MPC6 variants in the in vitro and cell based assays. We are waiting to test all of the compounds simultaneously to minimize

American Cancer Society: the world's wealthiest "nonprofit" institution.

Science.gov (United States)

Epstein, S S

1999-01-01

The American Cancer Society is fixated on damage control--diagnosis and treatment--and basic molecular biology, with indifference or even hostility to cancer prevention. This myopic mindset is compounded by interlocking conflicts of interest with the cancer drug, mammography, and other industries. The "nonprofit" status of the Society is in sharp conflict with its high overhead and expenses, excessive reserves of assets and contributions to political parties. All attempts to reform the Society over the past two decades have failed; a national economic boycott of the Society is long overdue.

"It's the economy, stupid": strategies for improved cost containment in cancer treatment.

Science.gov (United States)

Sleijfer, S

2014-04-01

The advent of numerous novel antitumor compounds has improved the prognosis of many cancer patients but has also substantially increased the costs of cancer care and put more pressure on health-care budgets. This situation increasingly raises questions such as the extent to which these drugs offer value sufficient to justify their cost and how to accommodate the increasing costs of cancer care. Here I look at the various aspects that affect cancer care economics and offer potential solutions.

Heterocyclic Anticancer Compounds: Recent Advances and the Paradigm Shift towards the Use of Nanomedicine's Tool Box.

Science.gov (United States)

Martins, Pedro; Jesus, João; Santos, Sofia; Raposo, Luis R; Roma-Rodrigues, Catarina; Baptista, Pedro Viana; Fernandes, Alexandra R

2015-09-16

The majority of heterocycle compounds and typically common heterocycle fragments present in most pharmaceuticals currently marketed, alongside with their intrinsic versatility and unique physicochemical properties, have poised them as true cornerstones of medicinal chemistry. Apart from the already marketed drugs, there are many other being investigated for their promising activity against several malignancies. In particular, anticancer research has been capitalizing on the intrinsic versatility and dynamic core scaffold of these compounds. Nevertheless, as for any other promising anticancer drugs, heterocyclic compounds do not come without shortcomings. In this review, we provide for a concise overview of heterocyclic active compounds and families and their main applications in medicine. We shall focus on those suitable for cancer therapy while simultaneously addressing main biochemical modes of action, biological targets, structure-activity relationships as well as intrinsic limitation issues in the use of these compounds. Finally, considering the advent of nanotechnology for effective selective targeting of drugs, we shall discuss fundamental aspects and considerations on nanovectorization of such compounds that may improve pharmacokinetic/pharmacodynamic properties of heterocycles.

Cancer Drug Development: New Targets for Cancer Treatment.

Science.gov (United States)

Curt

1996-01-01

cancer drug screening and cancer drug development. At the NCI, for example, the old in vivo mouse screen using mouse lymphomas has been shelved; it discovered compounds with some activity in lymphomas, but not the common solid tumors of adulthood. It has been replaced with an initial in vitro screen of some sixty cell lines, representing the common solid tumors-ovary, G.I., lung, breast, CNS, melanoma and others. The idea was to not only discover new drugs with specific anti-tumor activity but also to use the small volumes required for in vitro screening as a medium to screen for new natural product compounds, one of the richest sources of effective chemotherapy. The cell line project had an unexpected dividend. The pattern of sensitivity in the panel predicted the mechanism of action of unknown compounds. An antifolate suppressed cell growth of the different lines like other antifolates, anti-tubulin compounds suppressed like other anti-tubulins, and so on. It now became possible, at a very early stage of cancer drug screening, to select for drugs with unknown-and potentially novel-mechanisms of action. The idea was taken to the next logical step, and that was to characterize the entire panel for important molecular properties of human malignancy: mutations in the tumor suppressor gene p53, expression of important oncogenes like ras or myc, the gp170 gene which confers multiple drug resistance, protein-specific kinases, and others. It now became possible to use the cell line panel as a tool to detect new drugs which targeted a specific genetic property of the tumor cell. Researchers can now ask whether a given drug is likely to inhibit multiple drug resistance or kill cells which over-express specific oncogenes at the earliest phase of drug discovery. In this issue of The Oncologist, Tom Connors celebrates the fiftieth anniversary of cancer chemotherapy. His focus is on the importance of international collaboration in clinical trials and the negative impact of

Phytosterols: natural compounds with established and emerging health benefits

Directory of Open Access Journals (Sweden)

Trautwein Elke A.

2007-09-01

Full Text Available Phytosterols (plant sterols and stanols are naturally occurring compounds which are found in all foods of plant origin. The term phytosterols refers to more than 200 different compounds. The most abundant ones in the human diet are sitosterol and campesterol. Their saturated counterparts, sitostanol and campestanol, are found in much lower amounts. Good food sources of phytosterols include vegetable oils, cereal grains, nuts, legumes, and fruits and vegetables. Phytosterols are structurally similar to cholesterol. Despite this structural similarity, they are not absorbed in significant quantities. Absorption is less than 2% for phytosterols, while it is 30-60% for cholesterol. Phytosterols are known to have various bioactive properties, which may have an impact on human health, and as such boosted interest in phytosterols in the past decade. The most important benefit is their blood cholesterol-lowering effect via partial inhibition of intestinal cholesterol absorption. The recommended daily intake of 2 g of phytosterols reduces cholesterol absorption by 30-40% and LDL-cholesterol by 10% on average. Other claimed benefits of phytosterols are possible anti-atherogenic effects as well as, particularly for beta-sitosterol, immune stimulating and anti-inflammatory activities. Furthermore, there is emerging evidence suggesting that particularly plant sterols may have beneficial effects against the development of different types of cancers, like colorectal, breast and prostate cancers. It is not clear whether mechanisms other than the established cholesterol-lowering action of phytosterols as such also contribute to these potential health benefits.

Evaluation of phenolic compounds in mate (Ilex paraguariensis) processed by gamma radiation

Energy Technology Data Exchange (ETDEWEB)

Furgeri, C.; Nunes, T.C.F.; Fanaro, G.B. [Instituto de Pesquisas Energeticas Nucleares, IPEN-CNEN/SP, Centro de Tecnologia das Radiacoes-Laboratory de Deteccao de Alimentos Irradiados, Av. Professor Lineu Prestes, 2242, Cidade Universitaria, CEP: 05508-900 Sao Paulo (Brazil); Souza, M.F.F.; Bastos, D.H.M. [Faculdade de Saude Publica, FSP/USP, Departamento de Nutricao-Av. Dr. Arnaldo, 715, CEP: 01246-904 Sao Paulo (Brazil); Villavicencio, A.L.C.H. [Instituto de Pesquisas Energeticas Nucleares, IPEN-CNEN/SP, Centro de Tecnologia das Radiacoes-Laboratory de Deteccao de Alimentos Irradiados, Av. Professor Lineu Prestes, 2242, Cidade Universitaria, CEP: 05508-900 Sao Paulo (Brazil)], E-mail: villavic@ipen.br

2009-07-15

The radiation food processing has been demonstrating great effectiveness in the attack of pathogenic agents, while little compromising nutritional value and sensorial properties of foods. The mate (Ilex paraguariensis), widely consumed product in South America, generally in the form of infusions with hot or cold water, calls of chimarrao or terere, it is cited in literature as one of the best sources phenolic compounds. The antioxidants action of these constituent has been related to the protection of the organism against the free radicals, generated in alive, currently responsible for the sprouting of some degenerative illness as cancer, arteriosclerosis, rheumatic arthritis and cardiovascular clutters among others. The objective of that work was to evaluate the action of the processing for gamma radiation in phenolic compounds of terere beverage in the doses of 0, 3, 5, 7 and 10 kGy. The observed results do not demonstrate significant alterations in phenolic compounds of terere beverage processed by gamma radiation.

Evaluation of phenolic compounds in mate (Ilex paraguariensis) processed by gamma radiation

International Nuclear Information System (INIS)

Furgeri, C.; Nunes, T.C.F.; Fanaro, G.B.; Souza, M.F.F.; Bastos, D.H.M.; Villavicencio, A.L.C.H.

2009-01-01

The radiation food processing has been demonstrating great effectiveness in the attack of pathogenic agents, while little compromising nutritional value and sensorial properties of foods. The mate (Ilex paraguariensis), widely consumed product in South America, generally in the form of infusions with hot or cold water, calls of chimarrao or terere, it is cited in literature as one of the best sources phenolic compounds. The antioxidants action of these constituent has been related to the protection of the organism against the free radicals, generated in alive, currently responsible for the sprouting of some degenerative illness as cancer, arteriosclerosis, rheumatic arthritis and cardiovascular clutters among others. The objective of that work was to evaluate the action of the processing for gamma radiation in phenolic compounds of terere beverage in the doses of 0, 3, 5, 7 and 10 kGy. The observed results do not demonstrate significant alterations in phenolic compounds of terere beverage processed by gamma radiation.

Targeting multiple cannabinoid anti-tumour pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer.

Science.gov (United States)

Murase, Ryuichi; Kawamura, Rumi; Singer, Eric; Pakdel, Arash; Sarma, Pranamee; Judkins, Jonathon; Elwakeel, Eiman; Dayal, Sonali; Martinez-Martinez, Esther; Amere, Mukkanti; Gujjar, Ramesh; Mahadevan, Anu; Desprez, Pierre-Yves; McAllister, Sean D

2014-10-01

The psychoactive cannabinoid Δ(9) -tetrahydrocannabinol (THC) and the non-psychoactive cannabinoid cannabidiol (CBD) can both reduce cancer progression, each through distinct anti-tumour pathways. Our goal was to discover a compound that could efficiently target both cannabinoid anti-tumour pathways. To measure breast cancer cell proliferation/viability and invasion, MTT and Boyden chamber assays were used. Modulation of reactive oxygen species (ROS) and apoptosis was measured using dichlorodihydrofluorescein and annexin/propidium iodide, respectively, in combination with cell flow cytometry. Changes in protein levels were evaluated using Western analysis. Orthotopic and i.v. mouse models of breast cancer metastasis were used to test the activity of cannabinoids in vivo. CBD reduced breast cancer metastasis in advanced stages of the disease as the direct result of down-regulating the transcriptional regulator Id1. However, this was associated with moderate increases in survival. We therefore screened for analogues that could co-target cannabinoid anti-tumour pathways (CBD- and THC-associated) and discovered the compound O-1663. This analogue inhibited Id1, produced a marked stimulation of ROS, up-regulated autophagy and induced apoptosis. Of all the compounds tested, it was the most potent at inhibiting breast cancer cell proliferation and invasion in culture and metastasis in vivo. O-1663 prolonged survival in advanced stages of breast cancer metastasis. Developing compounds that can simultaneously target multiple cannabinoid anti-tumour pathways efficiently may provide a novel approach for the treatment of patients with metastatic breast cancer. © 2014 The British Pharmacological Society.

Prodrug strategy for cancer cell-specific targeting: A recent overview.

Science.gov (United States)

Zhang, Xian; Li, Xiang; You, Qidong; Zhang, Xiaojin

2017-10-20

The increasing development of targeted cancer therapy provides extensive possibilities in clinical trials, and numerous strategies have been explored. The prodrug is one of the most promising strategies in targeted cancer therapy to improve the selectivity and efficacy of cytotoxic compounds. Compared with normal tissues, cancer cells are characterized by unique aberrant markers, thus inactive prodrugs targeting these markers are excellent therapeutics to release active drugs, killing cancer cells without damaging normal tissues. In this review, we explore an integrated view of potential prodrugs applied in targeted cancer therapy based on aberrant cancer specific markers and some examples are provided for inspiring new ideas of prodrug strategy for cancer cell-specific targeting. Copyright © 2017. Published by Elsevier Masson SAS.

Rhein induces apoptosis of HCT-116 human colon cancer cells via ...

African Journals Online (AJOL)

Rhein, a major compound in rhubarb, has been found to have anti-tumor properties in many human cancer cells. However, the details about rhein suppressing the growth of human colon cancer cells remained elusive. In this paper, we explored the potential of rhein as a chemotherapeutic agent on HCT- 116 cells and ...

Antiproliferative, Antimicrobial and Apoptosis Inducing Effects of Compounds Isolated from Inula viscosa

Directory of Open Access Journals (Sweden)

Wamidh H. Talib

2012-03-01

Full Text Available The antiproliferative and antimicrobial effects of thirteen compounds isolated from Inula viscosa (L. were tested in this study. The antiproliferative activity was tested against three cell lines using the MTT assay. The microdilution method was used to study the antimicrobial activity against two Gram positive bacteria, two Gram negative bacteria and one fungus. The apoptotic activity was determined using a TUNEL colorimetric assay. Scanning electron microscopy was used to study the morphological changes in treated cancer cells and bacteria. Antiproliferative activity was observed in four flavonoids (nepetin, 3,3′-di-O-methylquercetin, hispidulin, and 3-O-methylquercetin. 3,3′-di-O-Methylquercetin and 3-O-methylquercetin showed selective antiproliferative activity against MCF-7 cells, with IC50 values of 10.11 and 11.23 µg/mL, respectively. Both compounds exert their antiproliferative effect by inducing apoptosis as indicted by the presence of DNA fragmentation, nuclear condensation, and formation of apoptotic bodies in treated cancer cells. The antimicrobial effect of Inula viscosa were also noticed in 3,3′-di-O-methylquercetin and 3-O-methyquercetin that inhibited Bacillus cereus at MIC of 62.5 and 125 µg/mL, respectively. Salmonella typhimurium was inhibited by both compounds at MIC of 125 µg/mL. 3,3′-di-O-Methylquercetin induced damage in bacterial cell walls and cytoplasmic membranes. Methylated quercetins isolated from Inula viscosa have improved anticancer and antimicrobial properties compared with other flavonoids and are promising as potential anticancer and antimicrobial agents.

Investments in cancer research awarded to UK institutions and the global burden of cancer 2000-2013: a systematic analysis.

Science.gov (United States)

Maruthappu, Mahiben; Head, Michael G; Zhou, Charlie D; Gilbert, Barnabas J; El-Harasis, Majd A; Raine, Rosalind; Fitchett, Joseph R; Atun, Rifat

2017-04-20

To systematically categorise cancer research investment awarded to United Kingdom (UK) institutions in the period 2000-2013 and to estimate research investment relative to disease burden as measured by mortality, disability-adjusted life years (DALYs) and years lived with disability (YLDs). Systematic analysis of all open-access data. Public and philanthropic funding to all UK cancer research institutions, 2000-2013. Number and financial value of cancer research investments reported in 2013 UK pounds (UK£). Mortality, DALYs and YLDs data were acquired from the Global Burden of Disease Study. A compound metric was adapted to estimate research investment relative to disease burden as measured by mortality, DALYs and YLDs. We identified 4299 funded studies with a total research investment of £2.4 billion. The highest fundings by anatomical sites were haematological, breast, prostate, colorectal and ovarian cancers. Relative to disease burden as determined by a compound metric combining mortality, DALYs and YLDs, gender-specific cancers were found to be highest funded-the five sites that received the most funding were prostate, ovarian, breast, mesothelioma and testicular cancer; the least well-funded sites were liver, thyroid, lung, upper gastrointestinal (GI) and bladder. Preclinical science accounted for 66.2% of award numbers and 62.2% of all funding. The top five areas of primary research focus by funding were pathogenesis, drug therapy, diagnostic, screening and monitoring, women's health and immunology. The largest individual funder was the Medical Research Council. In combination, the five lowest funded site-specific cancers relative to disease burden account for 47.9%, 44.3% and 20.4% of worldwide cancer mortality, DALYs and YLDs. Research funding for cancer is not allocated according to relative disease burden. These findings are in line with earlier published studies. Funding agencies and industry should openly document their research investments to

A new tellurium-containing amphiphilic molecule induces apoptosis in HCT116 colon cancer cells.

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Du, Peng; Saidu, Nathaniel Edward Bennett; Intemann, Johanna; Jacob, Claus; Montenarh, Mathias

2014-06-01

Chalcogen-based redox modulators over the years have attracted considerable attention as anti-cancer agents. New selenium- and tellurium-containing compounds with a polar head group and aryl-groups of various lengths have recently been reported as biologically active in several organisms. In the present study, we used the most active of the tellurium compound DP41, and its selenium counterpart DP31 to investigate their effects on the human cancer cell line HCT116. Cells were treated with DP41 or DP31 and the formation of superoxide radicals was determined using dihydroethidium. Cell cycle analysis and apoptosis was determined by cytofluorimetry. Proteins involved in ER signaling and apoptosis were determined by Western blot analysis and fluorescence microscopy. With 50μM of DP41, we observed an increase in O2(-) formation. There was, however, no such increase in O2(-) after treatment with the corresponding selenium compound under the same conditions. In the case of DP41, the production of O2(-) radicals was followed by an up-regulation of Nrf2, HO-1, phospho-eIF2α and ATF4. CHOP was also induced and cells entered apoptosis. Unlike the cancer cells, normal retinal epithelial ARPE-19 cells did not produce elevated levels of O2(-) radicals nor did they induce the ER signaling pathway or apoptosis. The tellurium-containing compound DP41, in contrast to the corresponding selenium compound, induces O2(-) radical formation and oxidative and ER stress responses, including CHOP activation and finally apoptosis. These results indicate that DP41 is a redox modulating agent with promising anti-cancer potentials. Copyright © 2014 Elsevier B.V. All rights reserved.

Antiproliferative and cell apoptosis-inducing activities of compounds from Buddleja davidii in Mgc-803 cells

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Wu Jian

2012-08-01

Full Text Available Abstract Background Buddleja davidii is widely distributed in the southwestern region of China. We have undertaken a systematic analysis of B. davidii as a Chinese traditional medicine with anticancer activity by isolating natural products for their activity against the human gastric cancer cell line Mgc-803 and the human breast cancer cell line Bcap-37. Results Ten compounds were extracted and isolated from B. davidii, among which colchicine was identified in B. davidii for the first time. The inhibitory activities of these compounds were investigated in Mgc-803, Bcap-37 cells in vitro by MTT [3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide] assay, and the results showed that luteolin and colchicine had potent inhibitory activities against the growth of Mgc-803 cells. Subsequent fluorescence staining and flow cytometry analysis indicated that these two compounds could induce apoptosis in Mgc-803 cells. The results also showed that the percentages of early apoptotic cells (Annexin V+/PI-, where PI is propidium iodide and late apoptotic cells (Annexin V+/PI+ increased in a dose- and time-dependent manner. After 36 h of incubation with luteolin at 20 μM, the percentages of cells were approximately 15.4% in early apoptosis and 43.7% in late apoptosis; after 36 h of incubation with colchicine at 20 μM, the corresponding values were 7.7% and 35.2%, respectively. Conclusions Colchicine and luteolin from B. davidii have potential applications as adjuvant therapies for treating human carcinoma cells. These compounds could also induce apoptosis in tumor cells.

Antiproliferative and cell apoptosis-inducing activities of compounds from Buddleja davidii in Mgc-803 cells.

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Wu, Jian; Yi, Wenshi; Jin, Linhong; Hu, Deyu; Song, Baoan

2012-08-31

Buddleja davidii is widely distributed in the southwestern region of China. We have undertaken a systematic analysis of B. davidii as a Chinese traditional medicine with anticancer activity by isolating natural products for their activity against the human gastric cancer cell line Mgc-803 and the human breast cancer cell line Bcap-37. Ten compounds were extracted and isolated from B. davidii, among which colchicine was identified in B. davidii for the first time. The inhibitory activities of these compounds were investigated in Mgc-803, Bcap-37 cells in vitro by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, and the results showed that luteolin and colchicine had potent inhibitory activities against the growth of Mgc-803 cells. Subsequent fluorescence staining and flow cytometry analysis indicated that these two compounds could induce apoptosis in Mgc-803 cells. The results also showed that the percentages of early apoptotic cells (Annexin V+/PI-, where PI is propidium iodide) and late apoptotic cells (Annexin V+/PI+) increased in a dose- and time-dependent manner. After 36 h of incubation with luteolin at 20 μM, the percentages of cells were approximately 15.4% in early apoptosis and 43.7% in late apoptosis; after 36 h of incubation with colchicine at 20 μM, the corresponding values were 7.7% and 35.2%, respectively. Colchicine and luteolin from B. davidii have potential applications as adjuvant therapies for treating human carcinoma cells. These compounds could also induce apoptosis in tumor cells.

Synthesis and biological evaluation of 2-(phenyl-3H-benzo[d]imidazole-5-carboxylic acids and its methyl esters as potent anti-breast cancer agents

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Chandrabose Karthikeyan

2017-05-01

Full Text Available A series of novel substituted 2-(phenyl-3H-benzo[d]imidazole-5-carboxylic acids (1a–1j and its methyl esters (2a–2f were synthesized and examined for their antiproliferative effects against three breast cancer cell lines (MDA-MB231, MDA-MB468 and MCF7 in vitro. Most of the compounds exhibited comparable or greater antiproliferative effects than the reference compound cisplatin. Compound 2e bearing 5-fluoro-2-hydroxyphenyl substituent was found to be the most active derivative of the series with GI50 values of 6.23, 4.09 and 0.18 μM against MDA-MB468, MDA-MB231 and MCF7 breast cancer cell lines, respectively. Our findings described here exemplify the usefulness of the title compounds as a lead for the development of more effective cancer therapeutics for the treatment of breast cancer.

Hazard Quotients, Hazard Indexes, and Cancer Risks of Toxic Metals in PM10 during Firework Displays

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Siwatt Pongpiachan

2018-04-01

Full Text Available Bonfire night is a worldwide phenomenon given to numerous annual celebrations characterised by bonfires and fireworks. Since Thailand has no national ambient air quality standards for metal particulates, it is important to investigate the impacts of particulate injections on elevations of air pollutants and the ecological health impacts resulting from firework displays. In this investigation, Pb and Ba were considered potential firework tracers because their concentrations were significantly higher during the episode, and lower than/comparable with minimum detection limits during other periods, indicating that their elevated concentrations were principally due to pyrotechnic displays. Pb/Ca, Pb/Al, Pb/Mg, and Pb/Cu can be used to pin-point emissions from firework displays. Air mass backward trajectories (72 h from the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT model indicated that areas east and north-east of the study site were the main sources of the airborne particles. Although the combined risk associated with levels of Pb, Cr, Co., Ni, Zn, As, Cd, V, and Mn was far below the standards mentioned in international guidelines, the lifetime cancer risks associated with As and Cr levels exceeded US-EPA guidelines, and may expose inhabitants of surrounding areas of Bangkok to an elevated cancer risk.

Metabolic profiling and correlation analysis for the determination of killer compounds of proliferating and clonogenic HRT-18 colon cancer cells from Lafoensia pacari.

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Reichert, Cristiane Loiva; da Silva, Denise Brentan; Carollo, Carlos Alexandre; Weffort-Santos, Almeriane Maria; de Moraes Santos, Cid Aimbiré

2018-06-18

Lafoensia pacari A. St.-Hil., belonging to the family Lythraceae and popularly known as 'dedaleira' and 'mangava-brava,' is a native tree of the Brazilian Cerrado, and its barks have been traditionally used as a tonic to treat inflammatory conditions, particularly related to gastric ulcers, wounds or fevers and various types of cancer. We have previously demonstrated the apoptogenic effects of the methanolic extract of L. pacari using various cancer cell lines. In the present study, this extract has been partitioned into fractions to identify the components that might be responsible for the apoptogenic effects using HRT-18 cells, which have been previously demonstrated to be sensitive to this extract. A standard methanolic extract was prepared and fractionated by centrifugal partition chromatography. The fractions were submitted to cytotoxicity and clonogenic assays to monitor the effects in parallel with LC-DAD-MS and statistical analyses to suggest the potential bioactive compounds. Besides ellagic acid, the primary constituent of the plant and also the biomarker of the species, one punicalin isomer, three pedunculagin I isomers, two castalagin isomers, three punicalagin HHDP-gallagyl-hexoside isomers, one ellagic acid deoxyhexose conjugate and one methyl ellagic acid deoxyhexose conjugate were putatively identified. The barks of L. pacari are rich in ellagic acid and various hydrolysable tannins, some of which were reported for the first time in this species, such as punicalagin and ellagitannins. This mixture of substances had the ability to kill proliferating cells and abrogate the growth of clonogenic cells in a similar manner shown by the methanolic extract of our previous study. The collective data reported herein suggest that the biological activities of the L. pacari barks used by the Cerrado's population to treat cancer conditions are due to the apoptogenic effects promoted by a mixed content of ellagitannins. Copyright © 2018. Published by Elsevier B.V.

Eugenol and its synthetic analogues inhibit cell growth of human cancer cells (Part I)

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Carrasco A, H.; Cardona, W. [Universidad Andres Bello, Vina del Mar (Chile). Dept. de Ciencias Quimicas]. E-mail: hcarrasco@unab.cl; Espinoza C, L.; Gallardo, C.; Catalan M, K. [Universidad Tecnica Federico Santa Maria, Valparaiso (Chile). Dept. de Quimica; Cardile, V.; Lombardo, L. [University of Catania (Italy). Dept. of Physiological Sciences; Cuellar F, M. [Universidad de Valparaiso (Chile). Facultad de Farmacia; Russo, A. [University of Catania (Italy). Dept. of Biological Chemistry, Medical Chemistry and Molecular Biology

2008-07-01

Eugenol (4-allyl-2-methoxyphenol) (1) has been reported to possess antioxidant and anticancer properties. In an attempt to enhance intrinsic activity of this natural compound, some derivatives were synthesized. Eugenol was extracted from cloves oil and further, the eugenol analogues (2-6) were obtained through acetylation and nitration reactions. Eugenol (1) and its analogues (2-6) were examined by in vitro model of cancer using two human cancer cell lines: DU-145 (androgeninsensitive prostate cancer cells) and KB (oral squamous carcinoma cells). Cell viability, by tetrazolium salts assay, was measured. Lactic dehydrogenase (LDH) release was also investigated to evaluate the presence of cell toxicity as a result of cell disruption, subsequent to membrane rupture. In the examined cancer cells, all compounds showed cell-growth inhibition activity. The obtained results demonstrate that the compounds 5-allyl-3-nitrobenzene-1,2-diol (3) and 4-allyl- 2-methoxy-5-nitrophenyl acetate (5) were significantly (p < 0,001) more active than eugenol, with IC{sub 50} values in DU-145 cells of 19.02 x 10{sup -6} and 21.5 x 10{sup -6} mol L{sup -1}, respectively, and in KB cells of 18.11 x 10{sup -6} and 21.26 x 10{sup -6} mol L{sup -1}, respectively, suggesting that the presence of nitro and hydroxyl groups could be important in the activity of these compounds. In addition, our results seem to indicate that apoptotic cell demise appears to be induced in KB and DU-145 cells. In fact, in our experimental conditions, no statistically significant increase in LDH release was observed in cancer cells treated with eugenol and its analogues. (author)

Apoptotic effect of chalcone derivatives of 2-acetylthiophene in human breast cancer cells.

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Fogaça, Tatiana B; Martins, Rosiane M; Begnini, Karine R; Carapina, Caroline; Ritter, Marina; de Pereira, Claudio M P; Seixas, Fabiana K; Collares, Tiago

2017-02-01

A variety of chalcones have demonstrated cytotoxic activity toward several cancer cell lines. This study aimed to investigate the cytotoxicity of four chalcones derivatives of 2-acetylthiophene in human breast cancer cell lines. MCF-7 and MDA-MB-231 cells were treated with synthesized chalcones and the cytotoxicity was evaluated by tetrazolium dye (MTT), live/dead, and DAPI assays. Chalcones significantly decreased MCF-7 and MDA-MB-231 cells viability in vitro in a dose dependent manner. After 48h treatment, the IC 50 values ranging from 5.52 to 34.23μM. Chalcone 3c displayed the highest cytotoxic activity from all the tested compounds. Cytotoxic effects of compounds were confirmed in the live/dead assay. In addition, DAPI staining revealed that these compounds induce death by apoptosis. The data speculate that chalcone derivatives of 2-acetylthiophene may represent a source of therapeutic agents for human breast cancer. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Controlling Magnetism of a Complex Metallic System Using Atomic Individualism

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Mudryk, Y.; Paudyal, D.; Pecharsky, V. K.; Gschneidner, K. A., Jr.; Misra, S.; Miller, G. J.

2010-08-01

When the complexity of a metallic compound reaches a certain level, a specific location in the structure may be critically responsible for a given fundamental property of a material while other locations may not play as much of a role in determining such a property. The first-principles theory has pinpointed a critical location in the framework of a complex intermetallic compound—Gd5Ge4—that resulted in a controlled alteration of the magnetism of this compound using precise chemical tools.

Proline-linked nitrosoureas as prolidase-convertible prodrugs in human breast cancer cells.

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Bielawski, Krzysztof; Bielawska, Anna; Słodownik, Tomasz; Bołkun-Skórnicka, Urszula; Muszyńska, Anna

2008-01-01

A number of novel proline-linked nitrosoureas (1-4) were synthesized and examined for cytotoxicity and influence on DNA and collagen biosynthesis in MDA-MB-231 and MCF-7 human breast cancer cells. Evaluation of the cytotoxicity of these compounds employing a MTT assay and inhibition of [(3)H]thymidine incorporation into DNA in both MDA-MB-231 and MCF-7 breast cancer cells demonstrated that compound 2, the most active of the series, proved to be only slightly less potent than carmustine. It has also been found that carmustine did not inhibit MCF&-7 cells prolidase activity, while compounds 1-4 significantly increased its activity, when used at 50-250 microM concentrations. Proline-linked nitrosoureas (1-4) also had lower ability to inhibit collagen biosynthesis in MCF-7 cells, compared to carmustine. The expression of beta(1)-integrin receptor and phosphorylated MAPK, ERK(1) and ERK(2) was significantly decreased in MCF-7 cells incubated for 24 h with 60 microM of compounds 2 and 4 compared to the control, untreated cells, whereas under the same conditions carmustine did not evoke any changes in expression of all these signaling proteins, as shown by Western immunoblot analysis. These results indicate the proline-linked nitrosoureas (1-4), represent multifunctional inhibitors of breast cancer cell growth and metabolism.

Constituents of the Rhizomes of Boesenbergia pandurata and Their Antiausterity Activities against the PANC-1 Human Pancreatic Cancer Line.

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Nguyen, Nhan Trung; Nguyen, Mai Thanh Thi; Nguyen, Hai Xuan; Dang, Phu Hoang; Dibwe, Dya Fita; Esumi, Hiroyasu; Awale, Suresh

2017-01-27

Human pancreatic cancer cell lines have a remarkable tolerance to nutrition starvation, which enables them to survive under a tumor microenvironment. The search for agents that preferentially inhibit the survival of cancer cells under low nutrient conditions represents a novel antiausterity strategy in anticancer drug discovery. In this investigation, a methanol extract of the rhizomes of Boesenbergia pandurata showed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions, with a PC 50 value of 6.6 μg/mL. Phytochemical investigation of this extract led to the isolation of 15 compounds, including eight new cyclohexene chalcones (1-8). The structures of the new compounds were elucidated by NMR spectroscopic data analysis. Among the isolated compounds obtained, isopanduratin A1 (14) and nicolaioidesin C (15) exhibited potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrition-deprived conditions, with PC 50 values of 1.0 and 0.84 μM, respectively.

Cytotoxic activity of erypogein d from erythrina poeppigiana (leguminosae) against cervical cancer (HeLa), breast cancer (MCF-7) and ovarian cancer (SKOV-3) cells

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Herlina, T.; Gaffar, S.; Widowati, W.

2018-05-01

Cancer is the uncontrolled growth of abnormal cells and continues to divide rapidly in the body. Current anticancer treatment usually causes many side effects. Natural products are then explored to be new alternatives for cancer treatment. Flavonoids have been known to possess medicinal properties, including anticancer. This study was performed to observe the cytotoxic activity of isoflavanone compound, erypogein D from Erythrina poeppigiana, toward cervical cancer (HeLa), breast cancer (MCF-7) and ovarian cancer (SKOV-3) cells. The cytotoxic activity of erypogein D was tested using MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3- carboxyme-thoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. The percentage of cell mortality was calculated and the IC50 was analyzed using probit analysis. The result showed that cytotoxic activity of the erypogein D against HeLa, SKOV-3, and MCF-7 cells had an IC50 value 225, 70.74, and 30.12 μM, respectively. Based on IC50 value can be concluded that erypogein D is the most cytotoxic to breast cancer MCF-7 cell. However the cytotoxic activity of erypogein D toward MCF7 is moderate.

The human volatilome: volatile organic compounds (VOCs) in exhaled breath, skin emanations, urine, feces and saliva.

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Amann, Anton; Costello, Ben de Lacy; Miekisch, Wolfram; Schubert, Jochen; Buszewski, Bogusław; Pleil, Joachim; Ratcliffe, Norman; Risby, Terence

2014-09-01

Breath analysis is a young field of research with its roots in antiquity. Antoine Lavoisier discovered carbon dioxide in exhaled breath during the period 1777-1783, Wilhelm (Vilém) Petters discovered acetone in breath in 1857 and Johannes Müller reported the first quantitative measurements of acetone in 1898. A recent review reported 1765 volatile compounds appearing in exhaled breath, skin emanations, urine, saliva, human breast milk, blood and feces. For a large number of compounds, real-time analysis of exhaled breath or skin emanations has been performed, e.g., during exertion of effort on a stationary bicycle or during sleep. Volatile compounds in exhaled breath, which record historical exposure, are called the 'exposome'. Changes in biogenic volatile organic compound concentrations can be used to mirror metabolic or (patho)physiological processes in the whole body or blood concentrations of drugs (e.g. propofol) in clinical settings-even during artificial ventilation or during surgery. Also compounds released by bacterial strains like Pseudomonas aeruginosa or Streptococcus pneumonia could be very interesting. Methyl methacrylate (CAS 80-62-6), for example, was observed in the headspace of Streptococcus pneumonia in concentrations up to 1420 ppb. Fecal volatiles have been implicated in differentiating certain infectious bowel diseases such as Clostridium difficile, Campylobacter, Salmonella and Cholera. They have also been used to differentiate other non-infectious conditions such as irritable bowel syndrome and inflammatory bowel disease. In addition, alterations in urine volatiles have been used to detect urinary tract infections, bladder, prostate and other cancers. Peroxidation of lipids and other biomolecules by reactive oxygen species produce volatile compounds like ethane and 1-pentane. Noninvasive detection and therapeutic monitoring of oxidative stress would be highly desirable in autoimmunological, neurological, inflammatory diseases and cancer

Dietary factors and cancer chemoprevention: An overview of obesity-related malignancies

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Murthy N

2009-01-01

Full Text Available Obesity is a growing health problem in developed nations and in countries that are in the process of westernization like India. Obesity is linked with several health disorders such as hypertension and cardiovascular diseases, Type 2 diabetes, dyslipidemia and certain cancers. Currently, obesity-related malignancies, e.g., cancers of the breast, prostate and colon are the leading cancers in the industrialized societies. An increased amount of fat or adipose tissue in an overweight or obese person probably influences the development of cancer by releasing several hormone-like factors or adipokines. The majority of adipokines are pro-inflammatory, which promote pathological conditions like insulin resistance and cancer. On the other hand, many recent studies have shown that adiponectin, an anti-inflammatory adipokine, has anti-cancer and insulin-sensitizing effects. Adiponectin exerts its physiological functions chiefly by activation of AMP kinase via adiponectin receptors. Interestingly, several fruits and vegetables may contain adiponectin-like molecules or may increase the biosynthesis of adiponectin in our body. Studies on adiponectin analogues or adiponectin receptor agonists are a promising area of cancer chemoprevention research. In general, fruits and vegetables contain various dietary substances such as vitamins, minerals (like calcium and selenium, fiber and phytochemicals or phenolic compounds (like flavonoids and vanilloids, which may act as anti-cancer agents. Similarly, several dietary constituents including phytochemicals may have anti-obesity effects. Consumption of such dietary compounds along with caloric restriction and physical activity may be helpful in preventing obesity-related cancers. For this review article, we searched PubMed primarily to get the relevant literature.

Identification and Characterization of Novel Antimitotic Compounds for the Treatment of Breast Cancer

National Research Council Canada - National Science Library

Roberge, Michel

2001-01-01

.... In year 1, we carried out a screen of over 30,000 extracts of terrestrial plants, algae and marine organisms, obtained 223 positive extracts, and isolated and identified active compounds from S of the positive extracts...

Rhodacyanine derivative selectively targets cancer cells and overcomes tamoxifen resistance.

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John Koren

Full Text Available MKT-077, a rhodacyanine dye, was shown to produce cancer specific cell death. However, complications prevented the use of this compound beyond clinical trials. Here we describe YM-1, a derivative of MKT-077. We found that YM-1 was more cytotoxic and localized differently than MKT-077. YM-1 demonstrated this cytotoxicity across multiple cancer cell lines. This toxicity was limited to cancer cell lines; immortalized cell models were unaffected. Brief applications of YM-1 were found to be non-toxic. Brief treatment with YM-1 restored tamoxifen sensitivity to a refractory tamoxifen-resistant MCF7 cell model. This effect is potentially due to altered estrogen receptor alpha phosphorylation, an outcome precipitated by selective reductions in Akt levels (Akt/PKB. Thus, modifications to the rhodocyanine scaffold could potentially be made to improve efficacy and pharmacokinetic properties. Moreover, the impact on tamoxifen sensitivity could be a new utility for this compound family.

Canine scent detection in the diagnosis of lung cancer: revisiting a puzzling phenomenon.

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Ehmann, R; Boedeker, E; Friedrich, U; Sagert, J; Dippon, J; Friedel, G; Walles, T

2012-03-01

Patient prognosis in lung cancer largely depends on early diagnosis. The exhaled breath of patients may represent the ideal specimen for future lung cancer screening. However, the clinical applicability of current diagnostic sensor technologies based on signal pattern analysis remains incalculable due to their inability to identify a clear target. To test the robustness of the presence of a so far unknown volatile organic compound in the breath of patients with lung cancer, sniffer dogs were applied. Exhalation samples of 220 volunteers (healthy individuals, confirmed lung cancer or chronic obstructive pulmonary disease (COPD)) were presented to sniffer dogs following a rigid scientific protocol. Patient history, drug administration and clinicopathological data were analysed to identify potential bias or confounders. Lung cancer was identified with an overall sensitivity of 71% and a specificity of 93%. Lung cancer detection was independent from COPD and the presence of tobacco smoke and food odours. Logistic regression identified two drugs as potential confounders. It must be assumed that a robust and specific volatile organic compound (or pattern) is present in the breath of patients with lung cancer. Additional research efforts are required to overcome the current technical limitations of electronic sensor technologies to engineer a clinically applicable screening tool.

Identification and bioactivity of compounds from the fungus Penicillium sp. CYE-87 isolated from a marine tunicate.

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Shaala, Lamiaa A; Youssef, Diaa T A

2015-03-25

In the course of our continuous interest in identifying bioactive compounds from marine microbes, we have investigated a tunicate-derived fungus, Penicillium sp. CYE-87. A new compound with the 1,4-diazepane skeleton, terretrione D (2), together with the known compounds, methyl-2-([2-(1H-indol-3-yl)ethyl]carbamoyl)acetate (1), tryptamine (3), indole-3-carbaldehyde (4), 3,6-diisobutylpyrazin-2(1H)-one (5) and terretrione C (6), were isolated from Penicillium sp. CYE-87. The structures of the isolated compounds were established by spectral analysis, including 1D (1H, 13C) and 2D (COSY, multiplicity edited-HSQC and HMBC) NMR and HRESIMS, as well as comparison of their NMR data with those in the literature. The compounds were evaluated for their antimigratory activity against the human breast cancer cell line (MDA-MB-231) and their antiproliferation activity against HeLa cells. Compounds 2 and 6 showed significant antimigratory activity against MDA-MB-231, as well as antifungal activity against C. albicans.

Heterocyclic Anticancer Compounds: Recent Advances and the Paradigm Shift towards the Use of Nanomedicine’s Tool Box

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