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Sample records for cancer cell extracts

  1. Natural grape extracts regulate colon cancer cells malignancy.

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    Signorelli, Paola; Fabiani, Carlotta; Brizzolari, Andrea; Paroni, Rita; Casas, Josefina; Fabriàs, Gemma; Rossi, Dario; Ghidoni, Riccardo; Caretti, Anna

    2015-01-01

    Natural dietary components are evolutionary-selected molecules able to control inflammation and cancerous transformation and progression. Because many studies assessed the beneficial properties of key molecules extracted from grapes, we aimed at investigating the properties of Liofenol™, a natural red wine lyophilized extract, devoid of alcohol and composed by a miscellaneous of components (polyphenols, flavonoids, anthocyanins). We proved that the colon cancer cell line HCT116 responded to Liofenol™ treatment by reducing their proliferation, in association with an increase of p53 and p21 cell cycle gate keepers. Liofenol™ increased dihydroceramides, sphingolipid mediators involved in cell cycle arrest and reduced proliferation rate. We observed a strong induction of antioxidant response, with the activation of the transcriptional factor Nrf2, involved in redox homeostasis and differentiation, without altering tumor sensitivity to chemotherapy. Liofenol™ induced an important morphology change in HCT116 cells, migration inhibition, undifferentiated stem/stem-like cells markers downregulation, and E-cadherin downregulation, interested in epithelia to mesenchymal malignant transition. We conclude that lyophilized grape extract, at dose comparable to putative dietary doses, can activate molecular pathways, involving Nrf2 signaling and the modulation of structural and signaling sphingolipid mediators that cooperate in promoting differentiation and reducing proliferation of digestive tract cancer cells.

  2. Danshen extract circumvents drug resistance and represses cell growth in human oral cancer cells.

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    Yang, Cheng-Yu; Hsieh, Cheng-Chih; Lin, Chih-Kung; Lin, Chun-Shu; Peng, Bo; Lin, Gu-Jiun; Sytwu, Huey-Kang; Chang, Wen-Liang; Chen, Yuan-Wu

    2017-12-29

    Danshen is a common traditional Chinese medicine used to treat neoplastic and chronic inflammatory diseases in China. However, the effects of Danshen on human oral cancer cells remain relatively unknown. This study investigated the antiproliferative effects of a Danshen extract on human oral cancer SAS, SCC25, OEC-M1, and KB drug-resistant cell lines and elucidated the possible underlying mechanism. We investigated the anticancer potential of the Danshen extract in human oral cancer cell lines and an in vivo oral cancer xenograft mouse model. The expression of apoptosis-related molecules was evaluated through Western blotting, and the concentration of in vivo apoptotic markers was measured using immunohistochemical staining. The antitumor effects of 5-fluorouracil and the Danshen extract were compared. Cell proliferation assays revealed that the Danshen extract strongly inhibited oral cancer cell proliferation. Cell morphology studies revealed that the Danshen extract inhibited the growth of SAS, SCC25, and OEC-M1 cells by inducing apoptosis. The Flow cytometric analysis indicated that the Danshen extract induced cell cycle G0/G1 arrest. Immunoblotting analysis for the expression of active caspase-3 and X-linked inhibitor of apoptosis protein indicated that Danshen extract-induced apoptosis in human oral cancer SAS cells was mediated through the caspase pathway. Moreover, the Danshen extract significantly inhibited growth in the SAS xenograft mouse model. Furthermore, the Danshen extract circumvented drug resistance in KB drug-resistant oral cancer cells. The study results suggest that the Danshen extract could be a potential anticancer agent in oral cancer treatment.

  3. The effect of Lactobacillus casei extract on cervical cancer cell lines

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    Kim, Soo-Nyung; Lee, Won Moo; Park, Kyoung Sik; Kim, Jong Bin; Han, Dae Jong

    2015-01-01

    Aim of the study Lactobacillus casei (L. casei) has been shown to inhibit the proliferation of several types of cancer in vivo, but its effect on cervical cells has not been reported. We incubated cells of the human cervical cell lines Caski and HeLa with extracts of L. casei and investigated its effects on the growth of the cells and possible synergy with anticancer drugs. Material and methods Cell-free extracts of L. casei were prepared and purified. Cultures of Caski and HeLa cells adhering to tissue culture plates were treated with L. casei extract. The effects of L. casei extract on the growth of cancer cells and its possible synergy with anti-cancer drugs in cervical cancer cell lines were investigated. The cells were treated with L. casei extract alone, anti-cancer drugs alone [doxorubicin, paclitaxel, 5-fluorouracil (5-FU), and cisplatin], or L. casei extract plus anti-cancer drugs. Results L. casei extract had no significant effect on the growth rate of the two cell lines. Anti-cancer drugs alone induced growth inhibition, but there was no synergistic effect of L. casei extract on growth inhibition. Conclusions L. casei extract does not have a potent effect on the viability of cervical cancer cells in vitro. In addition, L. casei extract has no synergistic effect on the inhibition of growth of cancer cells in the presence of anti-cancer drugs. PMID:26557779

  4. [Radiosensitization effect of black garlic extract on lung cancer cell line Lewis cells].

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    Yang, Gui-qing; Wang, Dong; Wang, Yi-shan; Wang, Yuan-yuan; Yang, Ke

    2013-08-01

    To explore the radiosensitization effect of black garlic extract (BGE) on lung cancer cell line Lewis cells. The inhibition rate of lung cancer cells after BGE action was detected by MTT. Effect of BGE combined radiotherapy on the colony formation rate was observed by cloning formation assay. Changes of the cell morphology were observed by Hoechst staining. Changes of the cell cycle were detected by flow cytometry. Real time PCR was used to detect mRNA expressions of bcl-2 and bax. BGE could have significant inhibitory action on the growth of lung cancer Lewis cells. The combination of BGE and radiotherapy (by 60Co gamma) significantly induced Lewis cells' apoptosis in G2/M stage, obviously decreased the expression of bcl-2, and up-regulated the expression of bax. BGE could sensitize the lung cancer Lewis cells to ionizing irradiation. This effect might be probably caused by changing the cell cycles and affecting expressions of bax and bcl-2.

  5. Human colon cancer HT-29 cell death responses to doxorubicin and Morus Alba leaves flavonoid extract.

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    Fallah, S; Karimi, A; Panahi, G; Gerayesh Nejad, S; Fadaei, R; Seifi, M

    2016-03-31

    The mechanistic basis for the biological properties of Morus alba flavonoid extract (MFE) and chemotherapy drug of doxorubicin on human colon cancer HT-29 cell line death are unknown. The effect of doxorubicin and flavonoid extract on colon cancer HT-29 cell line death and identification of APC gene expression and PARP concentration of HT-29 cell line were investigated. The results showed that flavonoid extract and doxorubicin induce a dose dependent cell death in HT-29 cell line. MFE and doxorubicin exert a cytotoxic effect on human colon cancer HT-29 cell line by probably promoting or induction of apoptosis.

  6. Cannabidiol rather than Cannabis sativa extracts inhibit cell growth and induce apoptosis in cervical cancer cells.

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    Lukhele, Sindiswa T; Motadi, Lesetja R

    2016-09-01

    Cervical cancer remains a global health related issue among females of Sub-Saharan Africa, with over half a million new cases reported each year. Different therapeutic regimens have been suggested in various regions of Africa, however, over a quarter of a million women die of cervical cancer, annually. This makes it the most lethal cancer amongst black women and calls for urgent therapeutic strategies. In this study we compare the anti-proliferative effects of crude extract of Cannabis sativa and its main compound cannabidiol on different cervical cancer cell lines. To achieve our aim, phytochemical screening, MTT assay, cell growth analysis, flow cytometry, morphology analysis, Western blot, caspase 3/7 assay, and ATP measurement assay were conducted. Results obtained indicate that both cannabidiol and Cannabis sativa extracts were able to halt cell proliferation in all cell lines at varying concentrations. They further revealed that apoptosis was induced by cannabidiol as shown by increased subG0/G1 and apoptosis through annexin V. Apoptosis was confirmed by overexpression of p53, caspase 3 and bax. Apoptosis induction was further confirmed by morphological changes, an increase in Caspase 3/7 and a decrease in the ATP levels. In conclusion, these data suggest that cannabidiol rather than Cannabis sativa crude extracts prevent cell growth and induce cell death in cervical cancer cell lines.

  7. Murraya koenigii leaf extract inhibits proteasome activity and induces cell death in breast cancer cells

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    Noolu Bindu

    2013-01-01

    Full Text Available Abstract Background Inhibition of the proteolytic activity of 26S proteasome, the protein-degrading machine, is now considered a novel and promising approach for cancer therapy. Interestingly, proteasome inhibitors have been demonstrated to selectively kill cancer cells and also enhance the sensitivity of tumor cells to chemotherapeutic agents. Recently, polyphenols/flavonoids have been reported to inhibit proteasome activity. Murraya koenigii Spreng, a medicinally important herb of Indian origin, has been used for centuries in the Ayurvedic system of medicine. Here we show that Murraya koenigii leaves (curry leaves, a rich source of polyphenols, inhibit the proteolytic activity of the cancer cell proteasome, and cause cell death. Methods Hydro-methanolic extract of curry leaves (CLE was prepared and its total phenolic content [TPC] determined by, the Folin-Ciocalteau’s method. Two human breast carcinoma cell lines: MCF-7 and MDA-MB-231 and a normal human lung fibroblast cell line, WI-38 were used for the studies. Cytotoxicity of the CLE was assessed by the MTT assay. We studied the effect of CLE on growth kinetics using colony formation assay. Growth arrest was assessed by cell cycle analysis and apoptosis by Annexin-V binding using flow cytometry. Inhibition of the endogenous 26S proteasome was studied in intact cells and cell extracts using substrates specific to 20S proteasomal enzymes. Results CLE decreased cell viability and altered the growth kinetics in both the breast cancer cell lines in a dose-dependent manner. It showed a significant arrest of cells in the S phase albeit in cancer cells only. Annexin V binding data suggests that cell death was via the apoptotic pathway in both the cancer cell lines. CLE treatment significantly decreased the activity of the 26S proteasome in the cancer but not normal cells. Conclusions Our study suggests M. koenigii leaves to be a potent source of proteasome inhibitors that lead to cancer cell death

  8. Murraya koenigii leaf extract inhibits proteasome activity and induces cell death in breast cancer cells.

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    Noolu, Bindu; Ajumeera, Rajanna; Chauhan, Anitha; Nagalla, Balakrishna; Manchala, Raghunath; Ismail, Ayesha

    2013-01-09

    Inhibition of the proteolytic activity of 26S proteasome, the protein-degrading machine, is now considered a novel and promising approach for cancer therapy. Interestingly, proteasome inhibitors have been demonstrated to selectively kill cancer cells and also enhance the sensitivity of tumor cells to chemotherapeutic agents. Recently, polyphenols/flavonoids have been reported to inhibit proteasome activity. Murraya koenigii Spreng, a medicinally important herb of Indian origin, has been used for centuries in the Ayurvedic system of medicine. Here we show that Murraya koenigii leaves (curry leaves), a rich source of polyphenols, inhibit the proteolytic activity of the cancer cell proteasome, and cause cell death. Hydro-methanolic extract of curry leaves (CLE) was prepared and its total phenolic content [TPC] determined by, the Folin-Ciocalteau's method. Two human breast carcinoma cell lines: MCF-7 and MDA-MB-231 and a normal human lung fibroblast cell line, WI-38 were used for the studies. Cytotoxicity of the CLE was assessed by the MTT assay. We studied the effect of CLE on growth kinetics using colony formation assay. Growth arrest was assessed by cell cycle analysis and apoptosis by Annexin-V binding using flow cytometry. Inhibition of the endogenous 26S proteasome was studied in intact cells and cell extracts using substrates specific to 20S proteasomal enzymes. CLE decreased cell viability and altered the growth kinetics in both the breast cancer cell lines in a dose-dependent manner. It showed a significant arrest of cells in the S phase albeit in cancer cells only. Annexin V binding data suggests that cell death was via the apoptotic pathway in both the cancer cell lines. CLE treatment significantly decreased the activity of the 26S proteasome in the cancer but not normal cells. Our study suggests M. koenigii leaves to be a potent source of proteasome inhibitors that lead to cancer cell death. Therefore, identification of active component(s) from the leaf

  9. Effects of Curcuma longa Extract on Telomerase Activity in Lung and Breast Cancer Cells

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    Nosratollah Zarghami

    2014-10-01

    Full Text Available Background: The purpose of this study is to evaluate the effect of Curcuma longa extract on the telomerase gene expression in QU-DB lung cancer and T47D breast cancer cell lines. Materials and Methods: The present study is an experimental research. Using 3 different phases n-hexane, dichloromethane and methanol, total extract of Curcuma longa in a serial dilution was prepared and three phases was analyzed for determining which phase has more curcuminoids. Then the extract cytotoxicity effect was tested on breast cancer cell line (T47D, and lung cancer cell line (QU-DB by 24, 48 and 72 h MTT (Dimethyl thiazolyl diphenyl tetrazolium assay. Then, the cells were treated with serial concentrations of the extract. Finally, total protein was extracted from the control and test groups, its quantity was determined and telomeric repeat amplification protocol (TRAP assay was performed for measurement of possible inhibition of the telomerase activity. Results: Cell viability and MTT-based cytotoxicity assay show that the total extract of Curcuma longa has cytotoxic effect with different IC50s in breast and lung cancer cell lines. Analysis of TRAP assay also shows a significant reduction in telomerase activity on both cancer cells with different levels. Conclusion: Curcuma longa extract has anti-proliferation and telomerase inhibitory effects on QU-DB lung cancer and T47D breast cancer cells with differences in levels of telomerase inhibition.

  10. Prolonged cytotoxic effect of aqueous extracts from dried viscum album on bladder cancer cells.

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    Hunziker-Basler, N; Zuzak, T J; Eggenschwiler, J; Rist, L; Simões-Wüst, A P; Viviani, A

    2007-03-01

    Aqueous extracts from whole dried mistletoe (Viscum album L., Iscucin) are often used in anti-cancer treatment. We studied the effect of extracts obtained from mistletoe bushes that grew on different host trees on bladder cancer cells by means of MTT-colorimetric cell proliferation/survival assays. The extracts possessed concentration-dependent cytotoxic properties whose extent varied with the host tree, but did not always correlate with the corresponding mistletoe lectin content. A 2-hours treatment of bladder cancer cells triggered a later, strong cytotoxic effect. This prolonged effect suggests that instillation with Iscucin has therapeutic potential for bladder cancer patients.

  11. Zanthoxylum fruit extract from Japanese pepper promotes autophagic cell death in cancer cells.

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    Nozaki, Reo; Kono, Toru; Bochimoto, Hiroki; Watanabe, Tsuyoshi; Oketani, Kaori; Sakamaki, Yuichi; Okubo, Naoto; Nakagawa, Koji; Takeda, Hiroshi

    2016-10-25

    Zanthoxylum fruit, obtained from the Japanese pepper plant (Zanthoxylum piperitum De Candolle), and its extract (Zanthoxylum fruit extract, ZFE) have multiple physiological activities (e.g., antiviral activity). However, the potential anticancer activity of ZFE has not been fully examined. In this study, we investigated the ability of ZFE to induce autophagic cell death (ACD). ZFE caused remarkable autophagy-like cytoplasmic vacuolization, inhibited cell proliferation, and ultimately induced cell death in the human cancer cell lines DLD-1, HepG2, and Caco-2, but not in A549, MCF-7, or WiDr cells. ZFE increased the level of LC3-II protein, a marker of autophagy. Knockdown of ATG5 using siRNA inhibited ZFE-induced cytoplasmic vacuolization and cell death. Moreover, in cancer cells that could be induced to undergo cell death by ZFE, the extract increased the phosphorylation of c-Jun N-terminal kinase (JNK), and the JNK inhibitor SP600125 attenuated both vacuolization and cell death. Based on morphology and expression of marker proteins, ZFE-induced cell death was neither apoptosis nor necrosis. Normal intestinal cells were not affected by ZFE. Taken together, our findings show that ZFE induces JNK-dependent ACD, which appears to be the main mechanism underlying its anticancer activity, suggesting a promising starting point for anticancer drug development.

  12. Ethanolic and aqueous extracts derived from Australian fungi inhibit cancer cell growth in vitro.

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    Beattie, Karren D; Ulrich, Rahel; Grice, I Darren; Uddin, Shaikh J; Blake, Tony B; Wood, Kyle A; Steele, Jules; Iu, Fontaine; May, Tom W; Tiralongo, Evelin

    2011-01-01

    Fifteen Australian macrofungi were investigated for cytotoxic activity. Ethanol, cold and hot water extracts of each species were screened for cytotoxic activity against normal mouse fibroblast cells (NIH/3T3), healthy human epithelial kidney cells (HEK-293), four cancer cell lines, gastric adenocarcinoma cells (AGS), two mammary gland adenocarcinoma cells (MDA-MB-231, MCF7) and colorectal adenocarcinoma cells (HT-29) with a validated MTT assay. Most extracts derived from Omphalotus nidiformis, Cordyceps cranstounii and Cordyceps gunnii demonstrated significant cytotoxic activity toward a variety of cancer cell lines. In contrast only some extracts from Coprinus comatus, Cordyceps hawkesii, Hypholoma fasciculare, Lepista nuda, Leratiomyces ceres and Ophiocordyceps robertsii displayed significant cytotoxic activity, which was usually selective for only one or two cancer cell lines tested. The least cytotoxic species evaluated in this study were Agaricus bitorquis, Coprinopsis atrametaria, Psathyrella asperospora, Russula clelandii, Tricholoma sp. AU2 and Xerula mundroola.

  13. Selective killing of cancer cells by Ashwagandha leaf extract and its component Withanone involves ROS signaling.

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    Nashi Widodo

    Full Text Available BACKGROUND AND PURPOSE: Ashwagandha is a popular Ayurvedic herb used in Indian traditional home medicine. It has been assigned a variety of health-promoting effects of which the mechanisms remain unknown. We previously reported the selective killing of cancer cells by leaf extract of Ashwagandha (i-Extract and its purified component Withanone. In the present study, we investigated its mechanism by loss-of-function screening (abrogation of i-Extract induced cancer cell killing of the cellular targets and gene pathways. METHODOLOGY/PRINCIPAL FINDINGS: Randomized ribozyme library was introduced into cancer cells prior to the treatment with i-Extract. Ribozymes were recovered from cells that survived the i-Extract treatment. Gene targets of the selected ribozymes (as predicted by database search were analyzed by bioinformatics and pathway analyses. The targets were validated for their role in i-Extract induced selective killing of cancer cells by biochemical and molecular assays. Fifteen gene-targets were identified and were investigated for their role in specific cancer cell killing activity of i-Extract and its two major components (Withaferin A and Withanone by undertaking the shRNA-mediated gene silencing approach. Bioinformatics on the selected gene-targets revealed the involvement of p53, apoptosis and insulin/IGF signaling pathways linked to the ROS signaling. We examined the involvement of ROS-signaling components (ROS levels, DNA damage, mitochondrial structure and membrane potential and demonstrate that the selective killing of cancer cells is mediated by induction of oxidative stress. CONCLUSION: Ashwagandha leaf extract and Withanone cause selective killing of cancer cells by induction of ROS-signaling and hence are potential reagents that could be recruited for ROS-mediated cancer chemotherapy.

  14. Selective killing of cancer cells by Ashwagandha leaf extract and its component Withanone involves ROS signaling.

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    Widodo, Nashi; Priyandoko, Didik; Shah, Navjot; Wadhwa, Renu; Kaul, Sunil C

    2010-10-21

    Ashwagandha is a popular Ayurvedic herb used in Indian traditional home medicine. It has been assigned a variety of health-promoting effects of which the mechanisms remain unknown. We previously reported the selective killing of cancer cells by leaf extract of Ashwagandha (i-Extract) and its purified component Withanone. In the present study, we investigated its mechanism by loss-of-function screening (abrogation of i-Extract induced cancer cell killing) of the cellular targets and gene pathways. Randomized ribozyme library was introduced into cancer cells prior to the treatment with i-Extract. Ribozymes were recovered from cells that survived the i-Extract treatment. Gene targets of the selected ribozymes (as predicted by database search) were analyzed by bioinformatics and pathway analyses. The targets were validated for their role in i-Extract induced selective killing of cancer cells by biochemical and molecular assays. Fifteen gene-targets were identified and were investigated for their role in specific cancer cell killing activity of i-Extract and its two major components (Withaferin A and Withanone) by undertaking the shRNA-mediated gene silencing approach. Bioinformatics on the selected gene-targets revealed the involvement of p53, apoptosis and insulin/IGF signaling pathways linked to the ROS signaling. We examined the involvement of ROS-signaling components (ROS levels, DNA damage, mitochondrial structure and membrane potential) and demonstrate that the selective killing of cancer cells is mediated by induction of oxidative stress. Ashwagandha leaf extract and Withanone cause selective killing of cancer cells by induction of ROS-signaling and hence are potential reagents that could be recruited for ROS-mediated cancer chemotherapy.

  15. Apoptotic Effect of the Urtica Dioica Plant Extracts on Breast Cancer Cell Line (MDA- MB- 468

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    A Mohammadi

    2015-09-01

    Full Text Available Background & objectives: Cancer is one of the most causes of mortality in worldwide. Components derived from natural plants that induce apoptosis are used for cancer treatment. Therefore investigation of different herbal components for new anti-cancer drug is one of the main research activities throughout the world. According to low cost, oral consumption and easy access to the public extracts of Urtica dioica, in this study we aimed to investigate the effectiveness of this herb on MDA-MB-468 breast cancer cells.   Methods: Cytotoxic effect of Urtica dioica extract was measured using MTT assays. To show induction of apoptosis by this plant TUNEL and DNA Fragmentation test were performed.   Results: In the present study dichloromethane extracts noticeably killed cancer cells. IC50 values related to human breast adenocarcinoma cell line MDA-MB-468 were 29.46±1.05 µg/ml in 24 hours and 15.54±1.04 µg/ml in 48 hours. TUNEL test and DNA Fragmentation assay showed apoptotic characteristic in the extract treated cells.   Conclusion: The results showed that MDA-MB-468 cells after treatment with dichloromethane extract of Urtica dioica, induces apoptosis in MDA-MB-468 cancer cells which may be useful in the treatment of cancer.

  16. Krill oil extract suppresses cell growth and induces apoptosis of human colorectal cancer cells.

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    Jayathilake, Abilasha Gayani; Senior, Paul Vincent; Su, Xiao Qun

    2016-08-30

    Colorectal cancer (CRC) is the third most common cancer in the world. The current available treatments for CRC include surgery, chemotherapy and radiotherapy. However, surgery is only useful when the disease is diagnosed at the earlier stage. Chemotherapy and radiotherapy are associated with numerous side effects that decrease the patients' quality of life. Safer, effective alternatives, such as natural compounds, to chemotherapy are desirable. This study assessed the efficacy of free fatty acid (FFA) extract of krill oil on three human CRC cells lines. HCT-15, SW-480 and Caco-2 cells were treated with the FFA extracts of krill oil and fish oil for 48 h while treatments with the bioactive omega-3 polyunsaturated fatty acids (LC n-3 PUFA) of these marine oils, eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3) in comparison with a n-6 PUFA, arachnoid acid (AA, C20:4n-6) were up to 72 h at the concentrations of 50, 100, 150 and 200 μM. Effects of all the treatments on cell proliferation were assessed using a water-soluble tetrazolium-1 (WST-1) assay kit at 24, 48 and 72 h. Effects of FFA extract of krill oil and EPA on apoptosis and mitochondrial membrane potential were determined using commercial kits after 48 h of treatment. Krill oil extract inhibited cell proliferation of all three cell lines in the similar manner as fish oil extract. A significant cell apoptosis and increase in mitochondrial membrane potential were observed after the treatment with krill oil extract. EPA at the concentration of 200 μM reduced significantly the proliferation of HCT-15 and SW-480 at 24, 48 and 72 h. In addition, EPA treatment (100 and 200 μM) resulted in significant cell apoptosis in all three cell lines. No significant changes were observed after treatment with DHA and AA. Our results indicate that the FFA extract of krill oil maybe an effective chemotherapeutic agent to suppress proliferation and induce apoptosis in CRC cells through its

  17. GC-MS based metabolomics of colon cancer cells using different extraction solvents.

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    Ibáñez, Clara; Simó, Carolina; Palazoglu, Mine; Cifuentes, Alejandro

    2017-09-15

    The increasing incidence of colorectal cancer enforces the development of novel methodologies and protocols to deepen in the molecular mechanisms that govern disease pathophysiological events. The aim of this work is to deepen in the optimum metabolite extraction protocol from adherent mammalian cells of colon cancer for high throughput metabolomics using gas chromatography coupled to mass spectrometry (GC-MS). GC-MS results showed that metabolic information obtained from colon cancer cells was highly dependent on metabolite extraction selection, which at the same time is extremely influenced by the analytical platform. A further purpose of this investigation is to uncover an unexplored portion of HT-29 colon cancer cells metabolome, complementary to other already explored by CE-MS and LC-MS methods. At this respect, a total of 150 metabolites were identified in HT-29 colon cancer cells by GC-MS. The extraction protocol with acetonitrile-isopropanol-water was the most appropriate for fatty acids and related pathways analysis. Most of the metabolites involved in pathways of amino acids, glutathione, amino sugars and other polar metabolites were better extracted with acidified water, although water extraction showed the best overall reproducibility. Although pathways involving nitrogenous bases could be investigated using organic or aqueous extracts, a higher number of metabolites involved in these pathways were identified in the aqueous extracts. In addition, metabolite extraction protocol was observed to be crucial for the determination of potentially interesting clusters of metabolites. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Anticancer effects of ethanolic neem leaf extract on prostate cancer cell line (PC-3).

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    Kumar, Suresh; Suresh, P K; Vijayababu, M R; Arunkumar, A; Arunakaran, J

    2006-04-21

    Prostate cancer (PC) is the most prevalent cancer and the leading cause of male cancer death. Azadirachta indica (neem tree) has been used successfully centuries to reduce tumors by herbalists throughout Southeast Asia. Here the present study indicated that an ethanolic extract of neem has been shown to cause cell death of prostate cancer cells (PC-3) by inducing apoptosis as evidenced by a dose-dependent increase in DNA fragmentation and a decrease in cell viability. Western blot studies indicated that treatment with neem extract showed decreased level of Bcl-2, which is anti-apoptotic protein and increased the level of Bax protein. So the neem extract could be potentially effective against prostate cancer treatment.

  19. Berberis libanotica Ehrenb extract shows anti-neoplastic effects on prostate cancer stem/progenitor cells.

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    El-Merahbi, Rabih; Liu, Yen-Nien; Eid, Assaad; Daoud, Georges; Hosry, Leina; Monzer, Alissar; Mouhieddine, Tarek H; Hamade, Aline; Najjar, Fadia; Abou-Kheir, Wassim

    2014-01-01

    Cancer stem cells (CSCs), including those of advanced prostate cancer, are a suggested reason for tumor resistance toward conventional tumor therapy. Therefore, new therapeutic agents are urgently needed for targeting CSCs. Despite the minimal understanding of their modes of action, natural products and herbal therapies have been commonly used in the prevention and treatment of many cancers. Berberis libanotica Ehrenb (BLE) is a plant rich in alkaloids which may possess anti-cancer activity and a high potential for eliminating CSCs. We tested the effect of BLE on prostate cancer cells and our data indicated that this extract induced significant reduction in cell viability and inhibited the proliferation of human prostate cancer cell lines (DU145, PC3 and 22Rv1) in a dose- and time-dependent manner. BLE extract induced a perturbation of the cell cycle, leading to a G0-G1 arrest. Furthermore, we noted 50% cell death, characterized by the production of high levels of reactive oxidative species (ROS). Inhibition of cellular migration and invasion was also achieved upon treatment with BLE extract, suggesting a role in inhibiting metastasis. Interestingly, BLE extract had a major effect on CSCs. Cells were grown in a 3D sphere-formation assay to enrich for a population of cancer stem/progenitor cells. Our results showed a significant reduction in sphere formation ability. Three rounds of treatment with BLE extract were sufficient to eradicate the self-renewal ability of highly resistant CSCs. In conclusion, our results suggest a high therapeutic potential of BLE extract in targeting prostate cancer and its CSCs.

  20. Berberis libanotica Ehrenb extract shows anti-neoplastic effects on prostate cancer stem/progenitor cells.

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    Rabih El-Merahbi

    Full Text Available Cancer stem cells (CSCs, including those of advanced prostate cancer, are a suggested reason for tumor resistance toward conventional tumor therapy. Therefore, new therapeutic agents are urgently needed for targeting CSCs. Despite the minimal understanding of their modes of action, natural products and herbal therapies have been commonly used in the prevention and treatment of many cancers. Berberis libanotica Ehrenb (BLE is a plant rich in alkaloids which may possess anti-cancer activity and a high potential for eliminating CSCs. We tested the effect of BLE on prostate cancer cells and our data indicated that this extract induced significant reduction in cell viability and inhibited the proliferation of human prostate cancer cell lines (DU145, PC3 and 22Rv1 in a dose- and time-dependent manner. BLE extract induced a perturbation of the cell cycle, leading to a G0-G1 arrest. Furthermore, we noted 50% cell death, characterized by the production of high levels of reactive oxidative species (ROS. Inhibition of cellular migration and invasion was also achieved upon treatment with BLE extract, suggesting a role in inhibiting metastasis. Interestingly, BLE extract had a major effect on CSCs. Cells were grown in a 3D sphere-formation assay to enrich for a population of cancer stem/progenitor cells. Our results showed a significant reduction in sphere formation ability. Three rounds of treatment with BLE extract were sufficient to eradicate the self-renewal ability of highly resistant CSCs. In conclusion, our results suggest a high therapeutic potential of BLE extract in targeting prostate cancer and its CSCs.

  1. Anticancer Effects of Extracts from the Fruit of Morinda Citrifolia (Noni) in Breast Cancer Cell Lines.

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    Sharma, K; Pachauri, S D; Khandelwal, K; Ahmad, H; Arya, A; Biala, P; Agrawal, S; Pandey, R R; Srivastava, A; Srivastav, A; Saxena, J K; Dwivedi, A K

    2016-03-01

    Morinda citrifolia L. (NONI) fruits have been used for thousands of years for the treatment of many health problems including cancer, cold, diabetes, flu, hypertension, and pain. Plant extracts have reported several therapeutic benefits, but extraction of individual compound from the extract often exhibits limited clinical utility as the synergistic effect of various natural ingredients gets lost. They generally constitute polyphenols and flavonoids. Studies have suggested that these phytochemicals, especially polyphenols, display high antioxidant properties, which help to reduce the risk of degenerative diseases, such as cancer and cardiovascular diseases. Several in-vitro and in-vivo studies have shown that Noni fruits have antioxidant, anti-inflammatory, anti-dementia, liver-protective, anticancer, analgesic, and immunomodulatory effects. Till date about 7 in vitro cancer studies have been done, but a detailed in vitro study including cell cycle and caspase activation assay on breast cancer cell line has not been done. In the present study different Noni fruit fractions have tested on cancer cell lines MCF-7, MDA-MB-231 (breast adenocarcinoma) and one non-cancer cell line HEK-293 (Human embryonic kidney). Out of which ethylacetate extract showed a higher order of in vitro anticancer activity profile. The ethylacetate extract strongly inhibited the proliferation of MCF-7, MDA-MB-231 and HEK-293 cell lines with IC50 values of 25, 35, 60 µg/ml respectively. The extract showed increase in apoptotic cells in MCF-7 and MDA-MB-231 cells and arrested the cell cycle in the G1/S phase in MCF-7 and G0/G1 phase in MDA-MB-231 cells. Noni extract also decreases the intracellular ROS generation and mitochondrial membrane potential. © Georg Thieme Verlag KG Stuttgart · New York.

  2. In vitro effects of extracts of extra virgin olive oil on human colon cancer cells.

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    Pampaloni, Barbara; Mavilia, Carmelo; Fabbri, Sergio; Romani, Annalisa; Ieri, Francesca; Tanini, Annalisa; Tonelli, Francesco; Brandi, Maria Luisa

    2014-01-01

    The Mediterranean diet is associated with a lower incidence of atherosclerosis, cardiovascular diseases, and some types of cancer. Recent interest has been focused on the biological activity of phenolic compounds present in extra virgin olive oils (EVOOs). Both in vivo and in vitro studies have shown that EVOO components have positive effects on metabolic parameters, such as plasma lipoproteins, oxidative damage, inflammatory markers, platelet function, and antimicrobial activity. We have investigated the possible interactions between 2 extracts of extra virgin olive oil and estrogen receptor β (ERβ) in an in vitro model of colon cancer. The qualification and quantification of the components of the 2 samples tested showed that phenolic compounds-hydroxytyrosol, secoiridoids, and lignans-are the major represented compounds. EVOO extracts were tested on a colon cancer cell line engineered to overexpress ERβ (HCT8-β8). By using custom made Oligo microarray, gene expression profiles of colon cancer cells challenged with EVOO-T extracts when compared with those of cells exposed to 17β-estradiol (17β-E2). This study demonstrated that the EVOO extracts tested showed an antiproliferative effect on colon cancer cells through the interaction with estrogen-dependent signals involved in tumor cell growth. Specifically, the ability of EVOO extracts to inhibit cell proliferation was superimposable to the activation of the ERβ receptor, similar to what was observed after 17β-E2 challenge.

  3. Leaf extracts from Nitraria retusa promote cell population growth of human cancer cells by inducing apoptosis.

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    Boubaker, Jihed; Bhouri, Wissem; Sghaier, Mohamed Ben; Bouhlel, Ines; Skandrani, Ines; Ghedira, Kamel; Chekir-Ghedira, Leila

    2011-10-31

    In this report the phytochemical profile of Nitraria. Retusa (N. Retusa) leaf extracts were identified and their ability to induce apoptosis in human chronic myelogenous erythroleukaemia (K562) was evaluated. Apoptosis of the human chronic myelogenous erythroleukaemia (K562) was evidenced by investigating DNA fragmentation, PARP cleavage and caspases 3 and 8 inducing activities, in the presence of N. retusa extracts. Our study revealed that the tested extracts from N. Retusa contain many useful bioactive compounds. They induced in a time-dependent manner the apoptosis the tested cancerous our cell line. This result was confirmed by ladder DNA fragmentation profile and PARP cleavage, as well as a release in caspase-3 and caspase-8 level. Our results indicate that the tested compounds have a significant antiproliferative effect which may be due to their involvement in the induction of the extrinsic apoptosic pathway.

  4. Leaf extracts from Nitraria retusa promote cell population growth of human cancer cells by inducing apoptosis

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    Bouhlel Ines

    2011-10-01

    Full Text Available Abstract Background In this report the phytochemical profile of Nitraria. Retusa (N. Retusa leaf extracts were identified and their ability to induce apoptosis in human chronic myelogenous erythroleukaemia (K562 was evaluated. Methods Apoptosis of the human chronic myelogenous erythroleukaemia (K562 was evidenced by investigating DNA fragmentation, PARP cleavage and caspases 3 and 8 inducing activities, in the presence of N. retusa extracts. Results Our study revealed that the tested extracts from N. Retusa contain many useful bioactive compounds. They induced in a time-dependent manner the apoptosis the tested cancerous our cell line. This result was confirmed by ladder DNA fragmentation profile and PARP cleavage, as well as a release in caspase-3 and caspase-8 level. Conclusion Our results indicate that the tested compounds have a significant antiproliferative effect which may be due to their involvement in the induction of the extrinsic apoptosic pathway.

  5. Anti-Cancer Activity of Methanol Extracts of Cichorium Intybus on Human Breast Cancer SKBR3 Cell Line

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    Reza Mehrandish

    2016-11-01

    Full Text Available Background Breast cancer is the most prevalent cancer and the second cause of death among women around the world. In many cancers, including breast cancer, Fatty acid synthase (FASN gene expression is increased significantly. In breast cancer cell lines, expression of FASN is higher in HER2 positive cell line like SKBR3 than the others. FASN is the key enzyme for fatty acid synthesis de novo pathway and it is producing palmitate which is necessary for cell membrane formation. Cichorium intybus is a medicinal plant that effectively leads to inhibition of fatty acid synthase and thus reduces the percentage of survival of cancer cell lines. Objectives The aim of this study was to evaluate the effect of methanol extract of Chicorium intybus root on percentage of survival in SKBR3 cell line. Methods Human breast cancer SKBR3 cell line was cultured in DMEM medium. Methanol extract of Cichorium intybus root was extracted and different dilutions (200, 300, 400, 500 and 600µg/mL were added to cell culture. Cell viability was quantitated by MTT assay after 24, 48 and 72 hours. Results Cichorium intybus could decrease cell viability. The effects of extract on cell viability were observed after 24, 48 and 72 hours on SKBR3 cell line and IC50 was 800, 400 and 300 after 24, 48 and 72 hours of treatment, respectively. Conclusions Our study shows that methanol extract of Cichorium intybus has cytotoxic effects on tumor cells. This is a pilot work for further evaluation in the future.

  6. Antibacterial and Antimetastatic Potential of Diospyros lycioides Extract on Cervical Cancer Cells and Associated Pathogens

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    V. P. Bagla

    2016-01-01

    Full Text Available Cervical cancer is among the most prevalent forms of cancer in women worldwide. Diospyros lycioides was extracted using hexane, ethyl acetate, acetone, and methanol and finger print profiles were determined. The leaf material was tested for the presence of flavonoids, tannins, saponins, terpenoids, and cardiac glycosides using standard chemical methods and the presence of flavonoids and phenolics using thin layer chromatography. The total phenolic content was determined using Folin-Ciocalteu procedure. The four extracts were tested for antibacterial activity using bioautography against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Escherichia coli. The acetone extract with the highest number of antibacterial and antioxidant compounds was assessed for its cytotoxicity on BUD-8 cells using the real-time xCELLigence system and its potential effects on metastatic cervical cancer (HeLa cell migration and invasion were assessed using wound healing migration and invasion assays. The leaf extract tested positive for flavonoids, tannins, and terpenoids while the four different extracts tested in the antimicrobial assay contained constituents active against one or more of the organisms tested, except E. coli. The cytotoxicity of the acetone extract in real-time was concentration-dependent with potent ability to suppress the migration and invasion of HeLa cells. The finding demonstrates the acetone extract to contain constituents with antibacterial and antimetastatic effects on cervical cancer cells.

  7. Ethanolic Extract Cytotoxic Effect of Zingiber Afficinale in Breast Cancer (MCF7 Cell Line

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    J Tavakkol Afshari

    2010-07-01

    Full Text Available Introduction & Objective: Biological activities of Zingiber afficieale plants have been reported as possessing anticancer, antibacterial, anti ulcer, antifungal, and insecticidal properties. However, its antitumor effects haven't been studied in cancer cell lines. The aim of this study was to investigate the antitumor effect of zingiber afficieale on breast cancer cell lines. Materials & Methods: This experimental study was conducted in 2010 at Mashhad University of medical Sciences. Breast cancer cell line (MCF7 and normal connective tissue cell line (L929 were cultured in DMEM medium. Ethanolic extract of Zingiber afficinale was prepared and cell lines were treated with different concentration of extract (5000 to 78 µg. Cell viability was measured by MTT assay after 24, 48, and 72 hours. The collected data were statistically analyzed by SPSS software. Results: The effects of Zingiber afficinale on cell viability were observed after 48 hours on cell lines. Ginger doses in 2500 µg concentration inhibited 50% of cell growth (IC50 in cell lines after 48 hours. Conclusion: Our study revealed that fresh ginger extract has cytotoxic effects on tumor cells, but it doesn’t have any cytotoxic effect on normal cells. It seems that ginger could be considered as a promising chemotherapeutic agent in cancer treatment.

  8. Ethanolic periwinkle leaf extract reduces telomerase expression in T47D cancer cells

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    Endang Purwaningsih

    2015-08-01

    Full Text Available BACKGROUND Cancer cells have a relatively high telomerase activity and a lower p53 protein expression than normal cells, so that cancer cells have the ability to continue to proliferate and do not undergo apoptosis. One of the cancer treatments is chemotherapy using bioactive ingredients from synthesis or isolation of natural materials. One of the plants that have potential as anticancer agent is periwinkle (Catharanthus roseus L. The research objective was to evaluate the effect of ethanolic periwinkle leaf extract against p53 protein and telomerase expression in T47D cancer cells. METHODS An experimental study with controls was conducted involving T47D breast cancer cells. They were divided into 3 groups (control, ½ dose of IC50/26.849 µg/mL, and one dose of IC50/53.699 µg/mL at a cell density of 1 x 104 cells/well. Expression of p53 and telomerase was measured by the immunohistochemistry method. Data were analyzed using one-way ANOVA followed by a multiple comparison test. RESULTS Periwinkle leaf extract significantly increased p53 protein expression (p<0.05 at both treatment doses, ½ IC50 and IC50, compared to the control group and it highly significantly reduced telomerase expression (p<0.01, in comparison with the control group at both treatment doses. CONCLUSION Periwinkle leaf extract has potential as an anti-breast cancer agent by increasing p53 protein expression and inhibiting telomerase expression.

  9. Viability-reducing activity of Coryllus avellana L. extracts against human cancer cell lines.

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    Gallego, Ana; Metón, Isidoro; Baanante, Isabel V; Ouazzani, Jamal; Adelin, Emilie; Palazon, Javier; Bonfill, Mercedes; Moyano, Elisabeth

    2017-05-01

    The increasing rate of cancer incidence has encouraged the search for novel natural sources of anticancer compounds. The presence of small quantities of taxol and taxanes in Corylus avellana L. has impelled new potential applications for this plant in the field of biomedicine. In the present work, the cell viability-reducing activity of stems and leaves from three different hazel trees was studiedagainst three human-derived cancer cell lines (HeLa, HepG2 and MCF-7). Both leaf and stem extracts significantly reduced viability of the three cell lines either after maceration with methanol or using taxane extraction methods. Since maceration reduced cell viability to a greater extent than taxane extraction methods, we scaled up the maceration extraction process using a method for solid/liquid extraction (Zippertex technology). Methanol leaf extracts promoted a higher reduction in viability of all cell lines assayed than stem extracts. Fractionation of methanol leaf extracts using silica gel chormatography led to the purification and identification of two compounds by HPLC-MS and NMR: (3R,5R)-3,5-dihydroxy-1,7-bis(4-hydroxyphenyl) heptane 3-O-β-d-glucopyranoside and quercetin-3-O-rhamnoside. The isolated compounds decreased viability of HeLa and HepG2 cells to a greater extent than MCF-7 cells. Our results suggest a potential use of C. avellana extracts in the pharmacotherapy of cervical cancer and hepatocarcinoma and, to a lesser extent, breast cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Urtica dioica dichloromethane extract induce apoptosis from intrinsic pathway on human prostate cancer cells (PC3).

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    Mohammadi, A; Mansoori, B; Aghapour, M; Baradaran, B

    2016-03-31

    Prostate cancer is considered as the major cause of death among men around the world. There are a number of medicinal plants triggering apoptosis response in cancer cells, thus have a therapeutic potential. Therefore, further studies to characterize beneficial properties of these plants in order to introduce novel anti-cancer drugs are the interest of recent researches on the alternative medicine. On the other hand, due to traditional uses and availability of Urtica dioica extract, we decided to evaluate the efficacy of this medicinal herb on pc3 prostate cancer cell line. In the present study the cytotoxic effects of Urtica dioica extract were assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and trypan blue viability dye. Then, DNA fragmentation and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were exploited to measure cell death and apoptosis stage. The expression levels of caspase 3, caspase 9 and Bcl-2 genes were quantified by Real-Time PCR. Finally, Cell cycle was analyzed by flow cytometry. MTT assay showed that dichloromethanolic extract of Urtica dioica significantly inhibited the cell growth. According to the DNA fragmentation and TUNEL assay results, the herbal extract was able to induce apoptosis in prostate cancer cells. Our findings also demonstrated that the plant extract substantially increases the caspase 3 and 9 mRNA expression, while decreases Bcl-2. Cell cycle arrest was occurred in G2 stage, due to the results of flow cytometry. These results indicate that dichloromethanolic extract of Urtica dioica can successfully induce apoptosis in PC3 cells. Therefore, it could be used as a novel therapeutic candidate for prostate tumor treatment.

  11. Antiproliferative and apoptotic effects of chamomile extract in various human cancer cells.

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    Srivastava, Janmejai K; Gupta, Sanjay

    2007-11-14

    Chamomile (Matricaria chamomilla), a popular herb valued for centuries as a traditional medicine, has been used to treat various human ailments; however, its anticancer activity is unknown. We evaluated the anticancer properties of aqueous and methanolic extracts of chamomile against various human cancer cell lines. Exposure of chamomile extracts caused minimal growth inhibitory responses in normal cells, whereas a significant decrease in cell viability was observed in various human cancer cell lines. Chamomile exposure resulted in differential apoptosis in cancer cells but not in normal cells at similar doses. HPLC analysis of chamomile extract confirmed apigenin 7-O-glucoside as the major constituent of chamomile; some minor glycoside components were also observed. Apigenin glucosides inhibited cancer cell growth but to a lesser extent than the parent aglycone, apigenin. Ex vivo experiments suggest that deconjugation of glycosides occurs in vivo to produce aglycone, especially in the small intestine. This study represents the first reported demonstration of the anticancer effects of chamomile. Further investigations of the mechanism of action of chamomile are warranted in evaluating the potential usefulness of this herbal remedy in the management of cancer patients.

  12. [Grape seed extract inhibits the growth of prostate cancer PC-3 cells].

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    Huang, Ting-Ting; Shang, Xue-Jun; Yao, Gen-Hong; Ge, Jing-Ping; Teng, Wen-Hui; Sun, Yi; Huang, Yu-Feng

    2008-04-01

    To investigate the inhibitory effect of grape seed extract (GSE) on the growth of prostate cancer PC-3 cells. PC-3 cells were treated with GSE at the concentration of 100, 200 and 300 microg/ml for 24, 48 and 72 hours, respectively. The the inhibitory effect of GSE on the growth of the PC-3 cells and the kidney cells of SD rats was determined by MTT reduction assay, with primarily cultured kidney cells of 1-3 days old SD rats as the normal control. GSE significantly inhibited the growth of PC-3 cells in a concentration- and time-dependent manner, but had only a mild inhibitory effect on the kidney cells. GSE inhibits the growth of prostate cancer PC-3 cells and can be used as a new drug for the treatment of prostate cancer.

  13. The participation of singlet oxygen in a photocitotoxicity of extract from amazon plant to cancer cells

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    Tcibulnikova, Anna V.; Degterev, Igor A.; Bryukhanov, Valery V.; Roberto, Mantuanelly M.; Campos Pereira, F. D.; Marin-Morales, M. A.; Slezhkin, Vasily A.; Samusev, Ilya G.

    2018-01-01

    We have been searching for new photosensitizers (PS) for photodynamic therapy (PDT) of cancer based on extracts from Amazonian plants since 2009. In this paper, we demonstrate that, under certain conditions, the extract from fruits of the Amazonian palm Euterpe oleraceae (popular name Açaí) can serve as a PS for PDT treatment of murine breast cancer cells (4T1 cell line). We have been first to show directly that the photodynamic effect of plant PS is due to singlet oxygen.

  14. Selective killing of cancer cells by leaf extract of Ashwagandha: components, activity and pathway analyses.

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    Widodo, Nashi; Takagi, Yasuomi; Shrestha, Bhupal G; Ishii, Tetsuro; Kaul, Sunil C; Wadhwa, Renu

    2008-04-08

    Ashwagandha, also called as "Queen of Ayurveda" and "Indian ginseng", is a commonly used plant in Indian traditional medicine, Ayurveda. Its roots have been used as herb remedy to treat a variety of ailments and to promote general wellness. However, scientific evidence to its effects is limited to only a small number of studies. We had previously identified anti-cancer activity in the leaf extract (i-Extract) of Ashwagandha and demonstrated withanone as a cancer inhibitory factor (i-Factor). In the present study, we fractionated the i-Extract to its components by silica gel column chromatography and subjected them to cell based activity analyses. We found that the cancer inhibitory leaf extract (i-Extract) has, at least, seven components that could cause cancer cell killing; i-Factor showed the highest selectivity for cancer cells and i-Factor rich Ashwagandha leaf powder was non-toxic and anti-tumorigenic in mice assays. We undertook a gene silencing and pathway analysis approach and found that i-Extract and its components kill cancer cells by at least five different pathways, viz. p53 signaling, GM-CFS signaling, death receptor signaling, apoptosis signaling and G2-M DNA damage regulation pathway. p53 signaling was most common. Visual analysis of p53 and mortalin staining pattern further revealed that i-Extract, fraction F1, fraction F4 and i-Factor caused an abrogation of mortalin-p53 interactions and reactivation of p53 function while the fractions F2, F3, F5 work through other mechanisms.

  15. Molecular Mechanisms by Which a Fucus vesiculosus Extract Mediates Cell Cycle Inhibition and Cell Death in Pancreatic Cancer Cells

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    Ulf Geisen

    2015-07-01

    Full Text Available Pancreatic cancer is one of the most aggressive cancer entities, with an extremely poor 5-year survival rate. Therefore, novel therapeutic agents with specific modes of action are urgently needed. Marine organisms represent a promising source to identify new pharmacologically active substances. Secondary metabolites derived from marine algae are of particular interest. The present work describes cellular and molecular mechanisms induced by an HPLC-fractionated, hydrophilic extract derived from the Baltic brown seaweed Fucus vesiculosus (Fv1. Treatment with Fv1 resulted in a strong inhibition of viability in various pancreatic cancer cell lines. This extract inhibited the cell cycle of proliferating cells due to the up-regulation of cell cycle inhibitors, shown on the mRNA (microarray data and protein level. As a result, cells were dying in a caspase-independent manner. Experiments with non-dividing cells showed that proliferation is a prerequisite for the effectiveness of Fv1. Importantly, Fv1 showed low cytotoxic activity against non-malignant resting T cells and terminally differentiated cells like erythrocytes. Interestingly, accelerated killing effects were observed in combination with inhibitors of autophagy. Our in vitro data suggest that Fv1 may represent a promising new agent that deserves further development towards clinical application.

  16. Molecular Mechanisms by Which a Fucus vesiculosus Extract Mediates Cell Cycle Inhibition and Cell Death in Pancreatic Cancer Cells.

    Science.gov (United States)

    Geisen, Ulf; Zenthoefer, Marion; Peipp, Matthias; Kerber, Jannik; Plenge, Johannes; Managò, Antonella; Fuhrmann, Markus; Geyer, Roland; Hennig, Steffen; Adam, Dieter; Piker, Levent; Rimbach, Gerald; Kalthoff, Holger

    2015-07-20

    Pancreatic cancer is one of the most aggressive cancer entities, with an extremely poor 5-year survival rate. Therefore, novel therapeutic agents with specific modes of action are urgently needed. Marine organisms represent a promising source to identify new pharmacologically active substances. Secondary metabolites derived from marine algae are of particular interest. The present work describes cellular and molecular mechanisms induced by an HPLC-fractionated, hydrophilic extract derived from the Baltic brown seaweed Fucus vesiculosus (Fv1). Treatment with Fv1 resulted in a strong inhibition of viability in various pancreatic cancer cell lines. This extract inhibited the cell cycle of proliferating cells due to the up-regulation of cell cycle inhibitors, shown on the mRNA (microarray data) and protein level. As a result, cells were dying in a caspase-independent manner. Experiments with non-dividing cells showed that proliferation is a prerequisite for the effectiveness of Fv1. Importantly, Fv1 showed low cytotoxic activity against non-malignant resting T cells and terminally differentiated cells like erythrocytes. Interestingly, accelerated killing effects were observed in combination with inhibitors of autophagy. Our in vitro data suggest that Fv1 may represent a promising new agent that deserves further development towards clinical application.

  17. Apoptosis-mediated inhibition of human breast cancer cell proliferation by lemon citrus extract.

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    Alshatwi, Ali A; Shafi, Gowhar; Hasan, Tarique N; Al-Hazzani, Amal A; Alsaif, Mohammed A; Alfawaz, Mohammed A; Lei, K Y; Munshi, Anjana

    2011-01-01

    Dietary phytochemicals have a variety of antitumor properties. In the present study, the antitumor activity of methanolic extract of lemon fruit (lemon extract; LE) (LE) on the MCF-7 breast cancer cell line was investigated in vitro. Apoptotic cell death was analyzed using the TUNEL assay. In addition, the apoptosis mediated by LE extract in the MCF-7 cells was associated with the increased expression of the tumor suppressor p53 and caspase-3. Additionally, the expression of a pro-apoptotic gene, bax, was increased, and the expression of an anti-apoptotic gene, bcl-2, was decreased by LE extract treatment, resulting in a shift in the Bax:Bcl-2 ratio to one that favored apoptosis. The expression of a major apoptotic gene, caspase-3, was increased by LE extract treatment. In light of the above results, we concluded that LE extract can induce the apoptosis of MCF-7 breast cancer cells via Bax-related caspase-3 activation. This study provides experimental data that are relevant to the possible future clinical use of LE to treat breast cancer.

  18. The cytotoxic effect of Elephantopus scaber Linn extract against breast cancer (T47D) cells

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    Sulistyani, N.; Nurkhasanah

    2017-11-01

    Breast cancer is one of the main cause of death. Elephantopus scaber Linn (ES) which has been used as a traditional medicine contains an antitumor compounds. This study aimed to explore the active fraction from ethanolic extract of ES as anticancer and to determine its inhibition effect on the cell proliferation cycle of breast cancer (T47D) cells. The ES leaf was macerated with ethanol and then evaporated to get the concentrated extract. The extract was fractionated using petroleum ether, chloroform, and methanol respectively. The cytotoxic activity of each fraction was carried out with MTT method, and the inhibition of cell cycle test were observed by flowcytometry method. The result showed that ES and the fractions have cytotoxic activity against T47D cell lines with IC50 values of extract, petroleum ether, chloroform, and methanol fractions were 58.36±2.38, 132.17±9.69, 7.08±2.11, and 572.89±69.23 µg/mL. The inhibition effect of ethanol extract on the lifecycle of cells was occured in sub G1 phase. There was no prolonging of G1, S, G2/M and polyploidy phase of T47D cell lines. The chloroform fraction of ES is the most cytotoxic fraction against T47D cells without prolonging the cell lifecycle.

  19. Cytotoxic Activity of the Methanolic Extract of Turnera diffusa Willd on Breast Cancer Cells

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    Avelino-Flores, María del Carmen; Cruz-López, María del Carmen; Jiménez-Montejo, Fabiola E.; Reyes-Leyva, Julio

    2015-01-01

    Abstract Turnera diffusa Willd, commonly known as Damiana, is employed in traditional medicine as a stimulant, aphrodisiac, and diuretic. Its leaves and stems are used for flavoring and infusion. Damiana is considered to be safe for medicinal use by the FDA. Pharmacological studies have established the hypoglycemic, antiaromatase, prosexual, estrogenic, antibacterial, and antioxidant activity of T. diffusa. The aim of the present study was to evaluate the possible cytotoxic effect of extracts and organic fractions of this plant on five tumor cell lines (SiHa, C-33, Hep G2, MDA-MB-231, and T-47D) and normal human fibroblasts. The results show that the methanolic extract (TdM) displayed greater activity on MDA-MB-231 breast cancer cells (with an IC50 of 30.67 μg/mL) than on the other cancer cell lines. Four organic fractions of this extract exhibited activity on this cancer cell line. In the most active fraction (F4), two active compounds were isolated, arbutin (1) and apigenin (2). This is the first report of a cytotoxic effect by T. diffusa on cancer cells. The IC50 values suggest that the methanolic extract of T. diffusa has potential as an anticancer therapy. PMID:25299247

  20. Methanolic Extracts of Bitter Melon Inhibit Colon Cancer Stem Cells by Affecting Energy Homeostasis and Autophagy

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    Deep Kwatra

    2013-01-01

    Full Text Available Bitter melon fruit is recommended in ancient Indian and Chinese medicine for prevention/treatment of diabetes. However its effects on cancer progression are not well understood. Here, we have determined the efficacy of methanolic extracts of bitter melon on colon cancer stem and progenitor cells. Both, whole fruit (BMW and skin (BMSk extracts showed significant inhibition of cell proliferation and colony formation, with BMW showing greater efficacy. In addition, the cells were arrested at the S phase of cell cycle. Moreover, BMW induced the cleavage of LC3B but not caspase 3/7, suggesting that the cells were undergoing autophagy and not apoptosis. Further confirmation of autophagy was obtained when western blots showed reduced Bcl-2 and increased Beclin-1, Atg 7 and 12 upon BMW treatment. BMW reduced cellular ATP levels coupled with activation of AMP activated protein kinase; on the other hand, exogenous additions of ATP lead to revival of cell proliferation. Finally, BMW treatment results in a dose-dependent reduction in the number and size of colonospheres. The extracts also decreased the expression of DCLK1 and Lgr5, markers of quiescent, and activated stem cells. Taken together, these results suggest that the extracts of bitter melon can be an effective preventive/therapeutic agent for colon cancer.

  1. Anticancer potential of Hericium erinaceus extracts against particular human cancer cell lines

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    Younis AM

    2017-06-01

    Full Text Available Cancer is a leading cause of death worldwide. Cancer resulted in 8.2 million human deaths in 2012. It is expected that annual cancer cases will rise from 14 million in 2013 to 22 million within the next two decades. Mushrooms are extensively used as nutritional supplements in many countries. Moreover, mushrooms have many medicinal properties, including anticancer activity. In this study, the anticancer activity of different polar and non-polar extracts of Hericium erinaceus were evaluated against different human cancer cell lines including human liver carcinoma (Hep G2, the human colonic epithelial carcinoma (HCT 116, the human cervical cancer cells (HeLa and the human breast adenocarcinoma (MCF-7 using 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Furthermore, as a control, the cytotoxicity effect of the different extracts were tested against isolated mouse hepatocytes. It was observed that the extracts by water and methanol from fresh and lyophilized fruiting bodies of H. erinaceus had the strongest anticancer effect. In contrast, the extracts by ether and ethyl acetate from mycelia and broth of H. erinaceus showed lower anticancer activity against the tested carcinoma cell lines. The highest anticancer activity was recorded for aqueous extract of lyophilized fruiting bodies with half maximal inhibitory concentration (IC50 values of 6.1±0.2, 5.1±0.1, 5.7±0.2 and 5.8±0.3 µg/ml against Hep G2, HCT 116, HeLa and MCF-7 cells, respectively with non-significant effect on the normal mouse hepatocytes. To summarise, polar extracts of H. erinaceus can be good sources for isolating natural anticancer compounds. I recommend further chemical studies to isolate the active principles of the extract of H. erinaceus evaluated in the present.

  2. Medicinal Mushroom Extracts Possess Differential Antioxidant Activity and Cytotoxicity to Cancer Cells.

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    Elbatrawy, Eman Nasr; Ghonimy, Eglal AbdAllah; Alassar, Mahomud Mohammed; Wu, Fang-Sheng

    2015-01-01

    Many species of edible mushrooms are known to contain a wide array of compounds with high nutritional and medicinal values. However, these values vary widely among mushroom species because of the wide diversity of compounds with different solubilities to solvents used in extraction. We report here the comparison of antioxidant activity and cytotoxicity against cancer cells in extracts of Pleurotus ostreatus, P. sajor-caju, Agaricus campestris, and A. bisporus from 7 different solvents, including water, ethanol, ethyl acetate, acetone, chloroform, hexane, and petroleum ether. The extracts were analyzed for their antioxidant activities using the % DPPH (2,2-diphenyl-1-picrylhydrazylhydrate) scavenging activity method. Our results revealed that the water extracts exhibited the highest % DPPH scavenging activity in comparison to all other solvent extracts. The highest value was obtained from the water extract of P. sajor-caju (78.1%), and the lowest one was from the hexane extract of A. bisporus (0.8%). In general, extracts from nonpolar solvents exhibited much lower antioxidant activities than those from polar solvents. The cytotoxic effects of these extracts were evaluated using 2 cancer cell lines of larynx carcinoma (HEp-2) and breast carcinoma (MCF-7). When added into Hep-2 cells, the hexane extracts from P. ostreatus, P. sajor-caju, A. bisporus, and A. campestris yielded the highest IC50 values of 1.7 ± 1.56, 2.1 ± 2.82, 4.4 ± 1.71, and 2.2 ± 1.34 μg/mL, respectively, in comparison to all other solvent extracts. Similar IC50 values were obtained when the MCF-2 cancer cells were tested, suggesting that hexane is the preferred solvent to extract the anticancer compounds from these mushrooms. Our results also indicated that extracts from solvents with nonpolar or intermediate polarity were more potent than those with high polarity in their cytotoxicity against cancer cells, and extracts from different mushrooms by the same solvent possessed varied degrees of

  3. Anti-cancer effect of Annona Muricata Linn Leaves Crude Extract (AMCE) on breast cancer cell line.

    Science.gov (United States)

    Syed Najmuddin, Syed Umar Faruq; Romli, Muhammad Firdaus; Hamid, Muhajir; Alitheen, Noorjahan Banu; Nik Abd Rahman, Nik Mohd Afizan

    2016-08-24

    Annona muricata Linn which comes from Annonaceae family possesses many therapeutic benefits as reported in previous studies and to no surprise, it has been used in many cultures to treat various ailments including headaches, insomnia, and rheumatism to even treating cancer. However, Annona muricata Linn obtained from different cultivation area does not necessarily offer the same therapeutic effects towards breast cancer (in regards to its bioactive compound production). In this study, anti-proliferative and anti-cancer effects of Annona muricata crude extract (AMCE) on breast cancer cell lines were evaluated. A screening of nineteen samples of Annona muricata from different location was determined by MTT assay on breast cancer cell lines (MCF-7, MDA-MB-231, and 4 T1) which revealed a varied potency (IC50) amongst them. Then, based on the IC50 profile from the anti-proliferative assay, further downward assays such as cell cycle analysis, Annexin V/FITC, AO/PI, migration, invasion, and wound healing assay were performed only with the most potent leaf aqueous extract (B1 AMCE) on 4 T1 breast cancer cell line to investigate its anti-cancer effect. Then, the in vivo anti-cancer study was conducted where mice were fed with extract after inducing the tumor. At the end of the experiment, histopathology of tumor section, tumor nitric oxide level, tumor malondialdehyde level, clonogenic assay, T cell immunophenotyping, and proteome profiler analysis were performed. Annona muricata crude extract samples exhibited different level of cytotoxicity toward breast cancer cell lines. The selected B1 AMCE reduced the tumor's size and weight, showed anti-metastatic features, and induced apoptosis in vitro and in vivo of the 4 T1 cells. Furthermore, it decreased the level of nitric oxide and malondialdehyde in tumor while also increased the level of white blood cell, T-cell, and natural killer cell population. The results suggest that, B1 AMCE is a promising candidate for cancer

  4. Anti Tumoral Properties of Punica Granatum (Pomegranate) Peel Extract on Different Human Cancer Cells.

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    Modaeinama, Sina; Abasi, Mozhgan; Abbasi, Mehran Mesgari; Jahanban-Esfahlan, Rana

    2015-01-01

    Medicinal plants, especially examples rich in polyphenolic compounds, have been suggested to be chemopreventive on account of antioxidative properties. Punica granatum (PG) (pomegranate) is a well known fruit in this context, but its cytotoxicity in cancer cells has not been extensively studied. Here, we investigated the antiproliferative properties of a peel extract of PG from Iran in different human cancer cells. A methanolic extract of pomegranate peel (PPE) was prepared. Total phenolic content(TPC) and total flavonoid conetnt (TFC) were determined by colorimetric assays. Antioxidant activity was determined by DPPH radical scavenging activity. The cytotoxicity of different doses of PPE (0, 5, 20, 100, 250, 500, 1000 μg/ml) was evaluated by MTT assays with A549 (lung non small cell cancer), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer), and PC-3 (prostate adenocarcinoma) cells. Significant (Pcancer cells, PPE reduced the cell viability to values below 40%, even at the lowest doses. In all cases, IC50 was determined at doses below 5μg/ml. In this regard, MCF-7 breast adenocarcinoma cells were the most responsive cells to antiprolifreative effects of PPE with a maximum mean growth inhibition of 81.0% vs. 69.4%, 79.3% and 77.5% in SKOV3, PC-3 and A549 cells, respectively. Low doses of PPE exert potent anti-proliferative effects in different human cancer cells and it seems that MCF-7 breast adenocarcinoma cells are the most cells and SKOV3 ovarian cancer cells the least responsive in this regard. However, the mechanisms of action need to be addressed.

  5. Differential Response of Two Human Breast Cancer Cell Lines to the Phenolic Extract from Flaxseed Oil

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    Angela Sorice

    2016-03-01

    Full Text Available Many studies have evidenced that the phenolic components from flaxseed (FS oil have potential health benefits. The effect of the phenolic extract from FS oil has been evaluated on two human breast cancer cell lines, MCF7 and MDA-MB231, and on the human non-cancerous breast cell line, MCF10A, by SRB assay, cellular death, cell cycle, cell signaling, lipid peroxidation and expression of some key genes. We have evidenced that the extract shows anti-proliferative activity on MCF7 cells by inducing cellular apoptosis, increase of the percentage of cells in G0/G1 phase and of lipid peroxidation, activation of the H2AX signaling pathway, and upregulation of a six gene signature. On the other hand, on the MDA-MB2131 cells we verified only an anti-proliferative activity, a weak lipid peroxidation, the activation of the PI3K signaling pathway and an up-regulation of four genes. Overall these data suggest that the extract has both cytotoxic and pro-oxidant effects only on MCF7 cells, and can act as a metabolic probe, inducing differences in the gene expression. For this purpose, we have performed an interactomic analysis, highlighting the existing associations. From this approach, we show that the phenotypic difference between the two cell lines can be explained through their differential response to the phenolic extract.

  6. [Grape seed extract induces morphological changes of prostate cancer PC-3 cells].

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    Shang, Xue-Jun; Yin, Hong-Lin; Ge, Jing-Ping; Sun, Yi; Teng, Wen-Hui; Huang, Yu-Feng

    2008-12-01

    To observe the morphological changes of prostate cancer PC-3 cells induced by grape seed extract (GSE). PC-3 cells were incubated with different concentrations of GSE (100, 200 and 300 microg/ml) for 24, 48 and 72 hours, and then observed for morphological changes by invert microscopy, HE staining and transmission electron microscopy. The incubated PC-3 cells appeared round, small, wrinkled and broken under the invert microscope and exhibited the classical morphological characteristics of cell death under the electron microscope, including cell atrophy, increased vacuoles, crumpled nuclear membrane, and chromosome aggregation. GSE can cause morphological changes and induce necrosis and apoptosis of PC-3 cells.

  7. Exploring the Anticancer Activity of Grape Seed Extract on Skin Cancer Cell Lines A431

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    V. Mohansrinivasan

    2015-08-01

    Full Text Available In this study, grape seeds were extracted using ethyl acetate and petroleum ether by solvent-solvent extraction method. The phytochemical tests were performed to identify different phytochemical compounds present in the grape seed extract (GSE. Antibacterial activity of the GSE was determined using agar diffusion method against Gram- positive and Gram-negative bacteria. Gas chromatography-mass spectrometry (GC-MS and Fourier transform infrared spectroscopy (FTIR analysis was done to identify the presence of bioactive compounds and their functional groups. The GC-MS results revealed a total of four compounds, known to have potent activity against cancer cells, viz, squalene, the most potent compound found in ethyl acetate extract and diethyl phthalate, ethyl-9- cis -11- trans octadecadienoate and (R-(--14,-methyl-8-Hexadecyn-1-ol in petroleum ether extract. Cytotoxic activity of the GSE was observed against skin cancer cell lines A4321 using 3-(4, 5-dimethylthiazol-2-yl-2-5-diphenyl tetrazolium bromide MTT assay. The IC50 value of the GSE against A431 skin cancer cell line was 480 µg/mL. This is first such report against A4321 cell lines. The study gives the overall perception about importance of GSE in medicine and nutraceuticals purposes.

  8. Crude Garlic Extract Inhibits Cell Proliferation and Induces Cell Cycle Arrest and Apoptosis of Cancer Cells In Vitro.

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    Bagul, Mukta; Kakumanu, Srikanth; Wilson, Thomas A

    2015-07-01

    Garlic and its lipid-based extracts have played an important medicinal role in humans for centuries that includes antimicrobial, hypoglycemic, and lipid-lowering properties. The present study was to investigate the effects of crude garlic extract (CGE) on the proliferation of human breast, prostate, hepatic, and colon cancer cell lines and mouse macrophageal cells, not previously studied. The human cancer cell lines, such as hepatic (Hep-G2), colon (Caco-2), prostate (PC-3), and breast (MCF-7), were propagated at 37°C; air/CO2 (95:5 v/v) using the ATCC-formulated RPMI-1640 Medium and 10% fetal bovine serum (FBS), while the mouse macrophage cell line (TIB-71) was propagated at 37°C; air/CO2 (95:5 v/v) using the ATCC-formulated DMEM and 10% FBS. All cells were plated at a density of ∼5000 cells/well. After overnight incubation, the cells were treated with 0.125, 0.25, 0.5, or 1 μg/mL of CGE an additional 72 h. Inhibition of cell proliferation of 80-90% was observed for Hep-G2, MCF-7, TIB-71, and PC-3 cells, but only 40-55% for the Caco-2 cells when treated with 0.25, 0.5, or 1 μg/mL. In a coculture study of Caco-2 and TIB-71 cells, inhibition of cell proliferation of 90% was observed for Caco-2 cells compared to the 40-55% when cultured separately. CGE also induced cell cycle arrest and had a fourfold increase in caspase activity (apoptosis) in PC-3 cells when treated at a dose of 0.5 or 1 μg/mL. This investigation of CGE clearly highlights the fact that the lipid bioactive compounds in CGE have the potential as promising anticancer agents.

  9. Anti-Proliferative Effects of Siegesbeckia orientalis Ethanol Extract on Human Endometrial RL-95 Cancer Cells

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    Chi-Chang Chang

    2014-12-01

    Full Text Available Endometrial cancer is a common malignancy of the female genital tract. This study demonstrates that Siegesbeckia orientalis ethanol extract (SOE significantly inhibited the proliferation of RL95-2 human endometrial cancer cells. Treating RL95-2 cells with SOE caused cell arrest in the G2/M phase and induced apoptosis of RL95-2 cells by up-regulating Bad, Bak and Bax protein expression and down-regulation of Bcl-2 and Bcl-xL protein expression. Treatment with SOE increased protein expression of caspase-3, -8 and -9 dose-dependently, indicating that apoptosis was through the intrinsic and extrinsic apoptotic pathways. Moreover, SOE was also effective against A549 (lung cancer, Hep G2 (hepatoma, FaDu (pharynx squamous cancer, MDA-MB-231 (breast cancer, and especially on LNCaP (prostate cancer cell lines. In total, 10 constituents of SOE were identified by Gas chromatography-mass analysis. Caryophyllene oxide and caryophyllene are largely responsible for most cytotoxic activity of SOE against RL95-2 cells. Overall, this study suggests that SOE is a promising anticancer agent for treating endometrial cancer.

  10. Cytotoxic Activities against Breast Cancer Cells of Local Justicia gendarussa Crude Extracts.

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    Ayob, Zahidah; Mohd Bohari, Siti Pauliena; Abd Samad, Azman; Jamil, Shajarahtunnur

    2014-01-01

    Justicia gendarussa methanolic leaf extracts from five different locations in the Southern region of Peninsular Malaysia and two flavonoids, kaempferol and naringenin, were tested for cytotoxic activity. Kaempferol and naringenin were two flavonoids detected in leaf extracts using gas chromatography-flame ionization detection (GC-FID). The results indicated that highest concentrations of kaempferol and naringenin were detected in leaves extracted from Mersing with 1591.80 mg/kg and 444.35 mg/kg, respectively. Positive correlations were observed between kaempferol and naringenin concentrations in all leaf extracts analysed with the Pearson method. The effects of kaempferol and naringenin from leaf extracts were examined on breast cancer cell lines (MDA-MB-231 and MDA-MB-468) using MTT assay. Leaf extract from Mersing showed high cytotoxicity against MDA-MB-468 and MDA-MB-231 with IC50 values of 23 μg/mL and 40 μg/mL, respectively, compared to other leaf extracts. Kaempferol possessed high cytotoxicity against MDA-MB-468 and MDA-MB-231 with IC50 values of 23 μg/mL and 34 μg/mL, respectively. These findings suggest that the presence of kaempferol in Mersing leaf extract contributed to high cytotoxicity of both MDA-MB-231 and MDA-MB-468 cancer cell lines.

  11. Cytotoxicity and apoptotic cell death induced by Vitis vinifera peel and seed extracts in A431 skin cancer cells.

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    Grace Nirmala, J; Evangeline Celsia, S; Swaminathan, Akila; Narendhirakannan, R T; Chatterjee, Suvro

    2017-10-05

    Vitis vinifera. L is one of the most widely consumed fruits in the world and are rich in antioxidant abundant polyphenols. The present study was carried out to assess the antiproliferative and apoptotic effects of Vitis vinifera peel and seed extracts in an in vitro model using human epidermoid carcinoma A431 cell lines. Vitis vinifera peel and seed extracts were incubated with A431 cells to evaluate the antiproliferative, apoptotic effects and the morphological apoptotic changes induced by the extracts. Mitochondrial membrane potential was also measured after incubating the cells with extracts. At the inhibitory concentration (IC 50 ), grape seed extract (111.11 µg/mL) and grape peel extract (319.14 µg/mL) were incubated for 24 h with A431 cells. Vitis vinifera peel and seed extracts were able to impart cytotoxic effects, induced apoptosis and apoptotic morphological changes in A431 cells significantly (p peel and seed phytochemicals can selectively target cancer cells and the phytochemicals that are occluded can serve as potential anticancer agents providing better efficacy in killing cancer cells.

  12. Anticancer Effect of Ginger Extract against Pancreatic Cancer Cells Mainly through Reactive Oxygen Species-Mediated Autotic Cell Death.

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    Miho Akimoto

    Full Text Available The extract of ginger (Zingiber officinale Roscoe and its major pungent components, [6]-shogaol and [6]-gingerol, have been shown to have an anti-proliferative effect on several tumor cell lines. However, the anticancer activity of the ginger extract in pancreatic cancer is poorly understood. Here, we demonstrate that the ethanol-extracted materials of ginger suppressed cell cycle progression and consequently induced the death of human pancreatic cancer cell lines, including Panc-1 cells. The underlying mechanism entailed autosis, a recently characterized form of cell death, but not apoptosis or necroptosis. The extract markedly increased the LC3-II/LC3-I ratio, decreased SQSTM1/p62 protein, and enhanced vacuolization of the cytoplasm in Panc-1 cells. It activated AMPK, a positive regulator of autophagy, and inhibited mTOR, a negative autophagic regulator. The autophagy inhibitors 3-methyladenine and chloroquine partially prevented cell death. Morphologically, however, focal membrane rupture, nuclear shrinkage, focal swelling of the perinuclear space and electron dense mitochondria, which are unique morphological features of autosis, were observed. The extract enhanced reactive oxygen species (ROS generation, and the antioxidant N-acetylcystein attenuated cell death. Our study revealed that daily intraperitoneal administration of the extract significantly prolonged survival (P = 0.0069 in a peritoneal dissemination model and suppressed tumor growth in an orthotopic model of pancreatic cancer (P < 0.01 without serious adverse effects. Although [6]-shogaol but not [6]-gingerol showed similar effects, chromatographic analyses suggested the presence of other constituent(s as active substances. Together, these results show that ginger extract has potent anticancer activity against pancreatic cancer cells by inducing ROS-mediated autosis and warrants further investigation in order to develop an efficacious candidate drug.

  13. Extraction of Natural Antioxidants from the Thelephora ganbajun Mushroom by an Ultrasound-Assisted Extraction Technique and Evaluation of Antiproliferative Activity of the Extract against Human Cancer Cells

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    Dong-Ping Xu

    2016-10-01

    Full Text Available The Thelephora ganbajun mushroom has been found to be a potential rich source of natural antioxidants. In this study, an ultrasound-assisted extraction (UAE technique together with GRAS (generally recognized as safe solvents (ethanol and water was used to maximize the extraction of antioxidants from Thelephora ganbajun. Five extraction parameters (ethanol concentration, solvent to solid ratio, extraction time, temperature and ultrasound power were investigated by single-factor experiments, and then a central composite rotatable design was employed to study interaction of three key extraction parameters. The optimum conditions were as follows: 57.38% ethanol, 70.15 mL/g solvent to solid ratio, 10.58 min extraction time, 40 °C extraction temperature and 500 W ultrasound power. Under the optimum conditions, the antioxidant activity obtained was 346.98 ± 12.19 µmol Trolox/g DW, in accordance with the predicted value of 344.67 µmol Trolox/g DW. Comparison of UAE with conventional maceration and Soxhlet extraction, the UAE method showed stronger extract efficiency in a shorter extraction time. These results showed that UAE was an effective technique to extract antioxidants from Thelephora ganbajun. Furthermore, the extracts obtained under the optimized conditions exhibited antiproliferative activities toward human lung (A549, breast (MCF-7, liver (HepG2 and colon (HT-29 cancer cells, especially for liver and lung cancer cells. In addition, rutin, 2-hydrocinnamic acid and epicatechin were identified in the extract, which might contribute to antioxidant and antiproliferative activities.

  14. Extraction of Natural Antioxidants from the Thelephora ganbajun Mushroom by an Ultrasound-Assisted Extraction Technique and Evaluation of Antiproliferative Activity of the Extract against Human Cancer Cells

    Science.gov (United States)

    Xu, Dong-Ping; Zheng, Jie; Zhou, Yue; Li, Ya; Li, Sha; Li, Hua-Bin

    2016-01-01

    The Thelephora ganbajun mushroom has been found to be a potential rich source of natural antioxidants. In this study, an ultrasound-assisted extraction (UAE) technique together with GRAS (generally recognized as safe) solvents (ethanol and water) was used to maximize the extraction of antioxidants from Thelephora ganbajun. Five extraction parameters (ethanol concentration, solvent to solid ratio, extraction time, temperature and ultrasound power) were investigated by single-factor experiments, and then a central composite rotatable design was employed to study interaction of three key extraction parameters. The optimum conditions were as follows: 57.38% ethanol, 70.15 mL/g solvent to solid ratio, 10.58 min extraction time, 40 °C extraction temperature and 500 W ultrasound power. Under the optimum conditions, the antioxidant activity obtained was 346.98 ± 12.19 µmol Trolox/g DW, in accordance with the predicted value of 344.67 µmol Trolox/g DW. Comparison of UAE with conventional maceration and Soxhlet extraction, the UAE method showed stronger extract efficiency in a shorter extraction time. These results showed that UAE was an effective technique to extract antioxidants from Thelephora ganbajun. Furthermore, the extracts obtained under the optimized conditions exhibited antiproliferative activities toward human lung (A549), breast (MCF-7), liver (HepG2) and colon (HT-29) cancer cells, especially for liver and lung cancer cells. In addition, rutin, 2-hydrocinnamic acid and epicatechin were identified in the extract, which might contribute to antioxidant and antiproliferative activities. PMID:27706082

  15. Role of oxidative stress in cytotoxicity of grape seed extract in human bladder cancer cells.

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    Raina, Komal; Tyagi, Alpna; Kumar, Dileep; Agarwal, Rajesh; Agarwal, Chapla

    2013-11-01

    In present study, we evaluated grape seed extract (GSE) efficacy against bladder cancer and associated mechanism in two different bladder cancer cell lines T24 and HTB9. A significant inhibitory effect of GSE on cancer cell viability was observed, which was due to apoptotic cell death. Cell death events were preceded by vacuolar appearance in cytoplasm, which under electron microscopy was confirmed as swollen mitochondrial organelle and autophagosomes. Through detailed in vitro studies, we established that GSE generated oxidative stress that initiated an apoptotic response as indicated by the reversal of GSE-mediated apoptosis when the cells were pre-treated with antioxidants prior to GSE. However, parallel to a strong apoptotic cell death event, GSE also caused a pro-survival autophagic event as evidenced by tracking the dynamics of LC3-II within the cells. Since the pro-death apoptotic response was stronger than the pro-survival autophagy induction within the cells, cell eventually succumbed to cellular death after GSE exposure. Together, the findings in the present study are both novel and highly significant in establishing, for the first time, that GSE-mediated oxidative stress causes a strong programmed cell death in human bladder cancer cells, suggesting and advocating the effectiveness of this non-toxic agent against this deadly malignancy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Dichloromethane fractions of Scrophularia oxysepala extract induce apoptosis in MCF-7 human breast cancer cells.

    Science.gov (United States)

    Hosseini, Behnaz-Alsadat; Pasdaran, Ardalan; Kazemi, Tohid; Shanehbandi, Dariush; Karami, Hadi; Orangi, Mona; Baradaran, Behzad

    2015-01-29

    Breast cancer is a prevalent malignancy among women, especially in developing countries. A large number of anticancer agents with herbal origins have been reported. Hence, herbals may play an essential role in prevention and treatment of cancers. We investigated cytotoxic effects of dichloromethane fractions of Scrophularia oxysepala extract on the MCF-7 breast cancer cell line. The cytotoxic activity of Scrophularia oxysepala fractions on the MCF-7 cells was assessed using Trypan Blue dye exclusion and MTT (3-(4, 5-dimetylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide) assays. In addition, apoptosis induction was determined using TUNEL (terminal deoxy transferase (TdT)-mediated dUTP nick- end labeling) assay and DNA fragmentation analysis. Quantitative Real-Time PCR was also used for analyzing the changes in Caspase-3, Caspase-9, and Bcl-2 genes' expression. Results revealed an effective inhibition of growth and viability in MCF-7 cells treated with dichloromethane fractions. Cell death assay and DNA fragmentation analysis using the TUNEL test confirmed the induction of apoptosis in the MCF-7 cell line. Further, the fractions have resulted in an increased expression of Caspase-3 and Caspase-9 mRNA, which highlights the possibility of apoptosis in the treatments. The expression study of Caspase-9 mRNA confirmed that, the fractions have triggered apoptosis via intrinsic mitochondrial pathway. In summary, fractions of Scrophularia oxysepala extract were found to be promising in growth inhibition and induction of apoptosis in MCF-7 breast cancer cells.

  17. Cytotoxic activity of Piper cubeba extract in breast cancer cell lines.

    Science.gov (United States)

    Graidist, Potchanapond; Martla, Mananya; Sukpondma, Yaowapa

    2015-04-10

    This study aimed to evaluate the cytotoxicity of a crude extract of Piper cubeba against normal and breast cancer cell lines. To prepare the extract, P. cubeba seeds were ground, soaked in methanol and dichloromethane and isolated by column chromatography. Fractions were tested for cytotoxicity effects on normal fibroblast (L929), normal breast (MCF-12A) and breast cancer cell lines (MCF-7, MDA-MB-468 and MDA-MB-231). The most effective fraction was selected for DNA fragmentation assay to detect apoptotic activity. The results showed that the methanolic crude extract had a higher cytotoxic activity against MDA-MB-468 and MCF-7 than a dichloromethane crude extract. Then, the methanolic crude extract was separated into six fractions, designated A to F. Fraction C was highly active against breast cancer cell lines with an IC50 value less than 4 μg/mL. Therefore, Fraction C was further separated into seven fractions, CA to CG. The 1H-NMR profile showed that Fraction CE was long chain hydrocarbons. Moreover, Fraction CE demonstrated the highest activity against MCF-7 cells with an IC50 value of 2.69 ± 0.09 μg/mL and lower cytotoxicity against normal fibroblast L929 cells with an IC50 value of 4.17 ± 0.77 μg/mL. Finally, DNA fragmentation with a ladder pattern characteristic of apoptosis was observed in MCF-7, MDA-MB-468, MDA-MB-231 and L929 cells, but not in MCF-12A cells.

  18. Anticarcinogenic activity of polyphenolic extracts from grape stems against breast, colon, renal and thyroid cancer cells.

    Science.gov (United States)

    Sahpazidou, Despina; Geromichalos, George D; Stagos, Dimitrios; Apostolou, Anna; Haroutounian, Serkos A; Tsatsakis, Aristidis M; Tzanakakis, George N; Hayes, A Wallace; Kouretas, Dimitrios

    2014-10-15

    A major part of the wineries' wastes is composed of grape stems which are discarded mainly in open fields and cause environmental problems due mainly to their high polyphenolic content. The grape stem extracts' use as a source of high added value polyphenols presents great interest because this combines a profitable venture with environmental protection close to wine-producing zones. In the present study, at first, the Total Polyphenolic Content (TPC) and the polyphenolic composition of grape stem extracts from four different Greek Vitis vinifera varieties were determined by HPLC methods. Afterwards, the grape stem extracts were examined for their ability to inhibit growth of colon (HT29), breast (MCF-7 and MDA-MB-23), renal (786-0 and Caki-1) and thyroid (K1) cancer cells. The cancer cells were exposed to the extracts for 72 h and the effects on cell growth were evaluated using the SRB assay. The results indicated that all extracts inhibited cell proliferation, with IC₅₀ values of 121-230 μg/ml (MCF-7), 121-184 μg/ml (MDA-MD-23), 175-309 μg/ml (HT29), 159-314 μg/ml (K1), 180-225 μg/ml (786-0) and 134->400 μg/ml (Caki-1). This is the first study presenting the inhibitory activity of grape stem extracts against growth of colon, breast, renal and thyroid cancer cells. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Antiproliferation and induction of apoptosis by Moringa oleifera leaf extract on human cancer cells.

    Science.gov (United States)

    Sreelatha, S; Jeyachitra, A; Padma, P R

    2011-06-01

    Medicinal plants provide an inexhaustible source of anticancer drugs in terms of both variety and mechanism of action. Induction of apoptosis is the key success of plant products as anticancer agents. The present study was designed to determine the antiproliferative and apoptotic events of Moringa oleifera leaf extract (MLE) using human tumor (KB) cell line as a model system. KB cells were cultured in the presence of leaf extracts at various concentrations for 48 h and the percentage of cell viability was evaluated by MTT assay. MLE showed a dose-dependent inhibition of cell proliferation of KB cells. The antiproliferative effect of MLE was also associated with induction of apoptosis as well as morphological changes and DNA fragmentation. The morphology of apoptotic nuclei was quantified using DAPI and propidium iodide staining. The degree of DNA fragmentation was analyzed using agarose gel electrophoresis. In addition, MLE at various concentrations was found to induce ROS production suggesting modulation of redox-sensitive mechanism. Eventually, HPTLC analysis indicated the presence of phenolics such as quercetin and kaempferol. Thus, these findings suggest that the leaf extracts from M. oleifera had strong antiproliferation and potent induction of apoptosis. Thus, it indicates that M. oleifera leaf extracts has potential for cancer chemoprevention and can be claimed as a therapeutic target for cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Polyphenolic extract of InsP 5-ptase expressing tomato plants reduce the proliferation of MCF-7 breast cancer cells.

    Science.gov (United States)

    Alimohammadi, Mohammad; Lahiani, Mohamed Hassen; McGehee, Diamond; Khodakovskaya, Mariya

    2017-01-01

    In recent years, by extensive achievements in understanding the mechanisms and the pathways affected by cancer, the focus of cancer research is shifting from developing new chemotherapy methods to using natural compounds with therapeutic properties to reduce the adverse effects of synthetic drugs on human health. We used fruit extracts from previously generated human type I InsP 5-ptase gene expressing transgenic tomato plants for assessment of the anti-cancer activity of established genetically modified tomato lines. Cellular assays (MTT, Fluorescent microscopy, Flow Cytometry analysis) were used to confirm that InsP 5-ptase fruit extract was more effective for reducing the proliferation of breast cancer cells compared to wild-type tomato fruit extract. Metabolome analysis of InsP 5-ptase expressing tomato fruits performed by LC-MS identified tomato metabolites that may play a key role in the increased anti-cancer activity observed for the transgenic fruits. Total transcriptome analysis of cancer cells (MCF-7 line) exposed to an extract of transgenic fruits revealed a number of differently regulated genes in the cells treated with transgenic extract compared to untreated cells or cells treated with wild-type tomato extract. Together, this data demonstrate the potential role of the plant derived metabolites in suppressing cell viability of cancer cells and further prove the potential application of plant genetic engineering in the cancer research and drug discovery.

  1. Polyphenolic extract of InsP 5-ptase expressing tomato plants reduce the proliferation of MCF-7 breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Mohammad Alimohammadi

    Full Text Available In recent years, by extensive achievements in understanding the mechanisms and the pathways affected by cancer, the focus of cancer research is shifting from developing new chemotherapy methods to using natural compounds with therapeutic properties to reduce the adverse effects of synthetic drugs on human health. We used fruit extracts from previously generated human type I InsP 5-ptase gene expressing transgenic tomato plants for assessment of the anti-cancer activity of established genetically modified tomato lines. Cellular assays (MTT, Fluorescent microscopy, Flow Cytometry analysis were used to confirm that InsP 5-ptase fruit extract was more effective for reducing the proliferation of breast cancer cells compared to wild-type tomato fruit extract. Metabolome analysis of InsP 5-ptase expressing tomato fruits performed by LC-MS identified tomato metabolites that may play a key role in the increased anti-cancer activity observed for the transgenic fruits. Total transcriptome analysis of cancer cells (MCF-7 line exposed to an extract of transgenic fruits revealed a number of differently regulated genes in the cells treated with transgenic extract compared to untreated cells or cells treated with wild-type tomato extract. Together, this data demonstrate the potential role of the plant derived metabolites in suppressing cell viability of cancer cells and further prove the potential application of plant genetic engineering in the cancer research and drug discovery.

  2. Serenoa repens extract targets mitochondria and activates the intrinsic apoptotic pathway in human prostate cancer cells.

    Science.gov (United States)

    Baron, Antonella; Mancini, Mariangela; Caldwell, Elizabeth; Cabrelle, Anna; Bernardi, Paolo; Pagano, Francesco

    2009-05-01

    To investigate the effects of Serenoa repens extract (Sr) in human PC3 and LNCaP prostate cancer and MCF7 breast cancer cells, with specific emphasis on the role of the mitochondrial apoptotic pathway, as the molecular pathway through which Sr, a natural product of plant origin, induces death of prostate cancer cells in culture is still unknown. Cellular and mitochondrial structure and function, and the cell cycle, were analysed using light, electron and fluorescence microscopy, spectrophotometry and flow cytometry. Apoptosis was evaluated using biochemical and cytohistochemical methods. Cells treated with Sr underwent massive vacuolization and cytosolic condensation, followed by cell death only in the prostate lines. Within minutes of adding Sr to prostate cells, it caused opening of the permeability transition pore (PTP), which led to complete mitochondrial depolarization within 2 h, and to the appearance of small, pycnotic mitochondria. Release of cytochrome c and SMAC/Diablo to the cytosol was detectable after 4 h of treatment, while caspase 9 activation and poly(ADP-ribose) polymerase 1 cleavage occurred at 16 h, followed by appearance of a sub-G1 peak and apoptosis at 24 h. Sr selectively induces apoptotic cell death of prostate cancer cells through the intrinsic pathway, and activation of the mitochondrial PTP might play a central role in this process.

  3. Induction of apoptosis in cancer cell lines by the Red Sea brine pool bacterial extracts.

    Science.gov (United States)

    Sagar, Sunil; Esau, Luke; Holtermann, Karie; Hikmawan, Tyas; Zhang, Guishan; Stingl, Ulrich; Bajic, Vladimir B; Kaur, Mandeep

    2013-12-05

    Marine microorganisms are considered to be an important source of bioactive molecules against various diseases and have great potential to increase the number of lead molecules in clinical trials. Progress in novel microbial culturing techniques as well as greater accessibility to unique oceanic habitats has placed the marine environment as a new frontier in the field of natural product drug discovery. A total of 24 microbial extracts from deep-sea brine pools in the Red Sea have been evaluated for their anticancer potential against three human cancer cell lines. Downstream analysis of these six most potent extracts was done using various biological assays, such as Caspase-3/7 activity, mitochondrial membrane potential (MMP), PARP-1 cleavage and expression of γH2Ax, Caspase-8 and -9 using western blotting. In general, most of the microbial extracts were found to be cytotoxic against one or more cancer cell lines with cell line specific activities. Out of the 13 most active microbial extracts, six extracts were able to induce significantly higher apoptosis (>70%) in cancer cells. Mechanism level studies revealed that extracts from Chromohalobacter salexigens (P3-86A and P3-86B(2)) followed the sequence of events of apoptotic pathway involving MMP disruption, caspase-3/7 activity, caspase-8 cleavage, PARP-1 cleavage and Phosphatidylserine (PS) exposure, whereas another Chromohalobacter salexigens extract (K30) induced caspase-9 mediated apoptosis. The extracts from Halomonas meridiana (P3-37B), Chromohalobacter israelensis (K18) and Idiomarina loihiensis (P3-37C) were unable to induce any change in MMP in HeLa cancer cells, and thus suggested mitochondria-independent apoptosis induction. However, further detection of a PARP-1 cleavage product, and the observed changes in caspase-8 and -9 suggested the involvement of caspase-mediated apoptotic pathways. Altogether, the study offers novel findings regarding the anticancer potential of several halophilic bacterial

  4. Apoptotic and anti-angiogenic effects of Salvia triloba extract in prostate cancer cell lines.

    Science.gov (United States)

    Atmaca, Harika; Bozkurt, Emir

    2016-03-01

    Plants, due to their remarkable composition, are considered as natural resources of bioactive compounds with specific biological activities. Salvia genus (Lamiaceae) has been used around the world in complementary medicine since ancient times. We investigated the cytotoxic, apoptotic and anti-angiogenic effects of methanolic Salvia triloba extract (STE) in prostate cancer cells. Cell viability was evaluated by XTT; apoptosis was investigated by DNA fragmentation and caspase 3/7 activity assays. Changes in the angiogenic cytokine levels were investigated by human angiogenesis antibody array. Scratch assay was used to determine the cell motility. STE induced cytotoxicity and apoptosis in a concentration-dependent manner in both cancer cells; however, it was not cytotoxic to normal cells. Cell motility was reduced in PC-3, DU-145 and HUVEC cells by STE treatment. ANG, ENA-78, bFGF, EGF, IGF-1 and VEGF-D levels were significantly decreased by -2.9, -3.7, -1.7, -1.7, -2.0 and -1.8 fold in STE-treated DU-145 cells, however, ANG, IL-8, LEP, RANTES, TIMP-1, TIMP-2 and VEGF levels were significantly decreased by -5.1, -2.0, -2.4, -3.1, -1.5, -2.0 and -2.5 fold in PC-3 cells. These data suggest that STE might be a promising candidate for anti-tumor and anti-angiogenic treatment of prostate cancer.

  5. Hypericum perforatum L. extract - novel photosensitizer against human bladder cancer cells.

    Science.gov (United States)

    Stavropoulos, N E; Kim, A; Nseyo, U U; Tsimaris, I; Chung, T D; Miller, T A; Redlak, M; Nseyo, U O; Skalkos, D

    2006-07-03

    The polar methanolic fraction (PMF) of the Hypericum perforatum L. extract has recently been developed and tested as a novel, natural photosensitizer for use in the photodynamic therapy (PDT), and photodynamic diagnosis (PDD). PMF has been tested on HL-60 leukemic cells and cord blood hemopoietic progenitors. In the present study, the efficacy of PMF as a phototoxic agent against urinary bladder carcinoma has been studied using the T24 (high grade metastatic cancer), and RT4 (primary low grade papillary transitional cell carcinoma) human bladder cancer cells. Following cell culture incubation, PMF was excited using 630 nm laser light. The photosensitizer exhibited significant photocytotoxicity in both cell lines at a concentration of 60microg/ml, with 4-8 J/cm(2) light dose, resulting in cell destruction from 80% to 86%. At the concentration of 20microg/ml PMF was not active in either cell line. These results were compared with the results obtained in the same cell lines, under the same conditions with a clinically approved photosensitizer, Photofrin. Photofrin was used in the maximum clinically tolerable dose of 4microg/ml, and it was also excited with 630 nm laser light. In the T24 cell Photofrin exhibited slightly less photocytotocixity, compared with PMF, resulting in 77% cell death with 8J/cm(2) light dose. However, against the RT4 cells Photofrin resulted in minimal cell death (9%) with even 8J/cm(2) light dose. Finally, the type of cell death induced by PMF photoactivation was studied using flow cytometry and DNA laddering. Cell death by PMF photodynamic action in these two bladder cell lines is caused predominently by apoptosis. The reported significant photocytotoxicity, selective localization, natural abundance, easy, and inexpensive preparation, underscore that the PMF extract hold the promise of being a novel, effective PDT photosensitizer.

  6. Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines.

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    Tavakkol-Afshari, Jalil; Brook, Azam; Mousavi, Seyed Hadi

    2008-11-01

    Saffron (dried stigmas of Crocus sativus L.) has been used as a spice, food colorant and medicinal plant for millennia. In this study cytotoxic effect of saffron extract was evaluated in HepG2 and HeLa cell lines. Meanwhile role of apoptosis and ROS were explored. Malignant and non-malignant cells (L929) were cultured in DMEM medium and incubated with different concentrations of ethanolic saffron extract. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). ROS was measured using DCF-DA by flow cytometry analysis. Saffron could decrease cell viability in malignant cells as a concentration and time-dependent manner. The IC50 values against HeLa and HepG2 were determined 800 and 950 microg/ml after 48 h, respectively. Saffron induced a sub-G1 peak in flow cytometry histogram of treated cells compared to control indicating apoptotic cell death is involved in saffron toxicity. This toxicity was also independent of ROS production. It might be concluded that saffron could cause cell death in HeLa and HepG2 cells, in which apoptosis or programmed cell death plays an important role. Saffron could be also considered as a promising chemotherapeutic agent in cancer treatment in future.

  7. Aged black garlic extract induces inhibition of gastric cancer cell growth in vitro and in vivo.

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    Wang, Xin; Jiao, Fei; Wang, Qin-Wen; Wang, Juan; Yang, Ke; Hu, Rong-Rong; Liu, Han-Chen; Wang, Hong-Yang; Wang, Yi-Shan

    2012-01-01

    There is mounting evidence that garlic extracts possess significant anticancer actions. However, no studies have been reported on the effects of aged black garlic extracts (ABGE) on gastric cancer in vitro or in vivo. To examine the potential action of ABGE against gastric cancer, the present study evaluated its effect on the inhibition of cell proliferation and induction of apoptosis in SGC-7901 human gastric cancer cells. Additionally, we performed an in vivo study by inoculating the murine foregastric carcinoma cell line in Kunming mice and treating them with various doses of ABGE (0, 200, 400 and 800 mg/kg, intraperitoneally) for 2 weeks. Dose-dependent apoptosis was detected in ABGE-treated cells in in vitro studies. In tumor-bearing mice, significant antitumor effects of ABGE were observed, such as growth inhibition of inoculated tumors. Further investigation of serum superoxide dismutases, glutathione peroxidase, interleukin-2 and the increased indices of spleen and thymus indicated that the anticancer action of ABGE may be partly due to its antioxidant and immunomodulative effects.

  8. Green tea extract induces protective autophagy in A549 non-small lung cancer cell line

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    Magdalena Izdebska

    2015-12-01

    Full Text Available Background and objectives: For many decades, polyphenols, including green tea extract catechins, have been reported to exert multiple anti-tumor activities. However, to date the mechanisms of their action have not been completely elucidated. Thus, the aim of this study was to assess the effect of green tea extract on non-small lung cancer A549 cells. Material and methods: A549 cells following treatment with GTE were analyzed using the inverted light and fluorescence microscope. In order to evaluate cell sensitivity and cell death, the MTT assay and Tali image-based cytometer were used, respectively. Ultrastructural alterations were assessed using a transmission electron microscope.Results: The obtained data suggested that GTE, even at the highest dose employed (150 μM, was not toxic to A549 cells. Likewise, the treatment with GTE resulted in only a very small dose-dependent increase in the population of apoptotic cells. However, enhanced accumulation of vacuole-like structures in response to GTE was seen at the light and electron microscopic level. Furthermore, an increase in the acidic vesicular organelles and LC3-II puncta formation was observed under the fluorescence microscope, following GTE treatment. The analysis of the functional status of autophagy revealed that GTE-induced autophagy may provide self-protection against its own cytotoxicity, since we observed that the blockage of autophagy by bafilomycin A1 decreased the viability of A549 cells and potentiated necrotic cell death induction in response to GTE treatment.Conclusion: Collectively, our results revealed that A549 cells are insensitive to both low and high concentrations of the green tea extract, probably due to the induction of cytoprotective autophagy. These data suggest that a potential utility of GTE in lung cancer therapy may lie in its synergistic combinations with drugs or small molecules that target autophagy, rather than in monotherapy.

  9. Selective modulation of endoplasmic reticulum stress markers in prostate cancer cells by a standardized mangosteen fruit extract.

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    Gongbo Li

    Full Text Available The increased proliferation of cancer cells is directly dependent on the increased activity of the endoplasmic reticulum (ER machinery which is responsible for protein folding, assembly, and transport. In fact, it is so critical that perturbations in the endoplasmic reticulum can lead to apoptosis. This carefully regulated organelle represents a unique target of cancer cells while sparing healthy cells. In this study, a standardized mangosteen fruit extract (MFE was evaluated for modulating ER stress proteins in prostate cancer. Two human prostate cancer cell lines, 22Rv1 and LNCaP, and prostate epithelial cells (PrECs procured from two patients undergoing radical prostatectomy were treated with MFE. Flow cytometry, MTT, BrdU and Western blot were used to evaluate cell apoptosis, viability, proliferation and ER stress. Next, we evaluated MFE for microsomal stability and anti-cancer activity in nude mice. MFE induced apoptosis, decreased viability and proliferation in prostate cancer cells. MFE increased the expression of ER stress proteins. Interestingly, MFE selectively promotes ER stress in prostate cancer cells while sparing PrECs. MFE suppressed tumor growth in a xenograft tumor model without obvious toxicity. Mangosteen fruit extract selectively promotes endoplasmic reticulum stress in cancer cells while sparing non-tumorigenic prostate epithelial cells. Furthermore, in an in vivo setting mangosteen fruit extract significantly reduces xenograft tumor formation.

  10. Induction of Apoptosis in Endometrial Cancer (Ishikawa Cells by Pogostemon cablin Aqueous Extract (PCAE

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    Ching-Chou Tsai

    2015-06-01

    Full Text Available Pogostemon cablin (PC is a traditional herbal medicine used in the treatment of the common cold, nausea, diarrhea, and even for headaches and fever. However, the mechanisms underlying the anti-proliferative activity of PC in endometrial cancer (EC cells have yet to be fully elucidated. This study investigated the anticancer effects of an aqueous extract of Pogostemon cablin (PCAE, specifically induced apoptosis in EC (Ishikawa cells. Proliferation of EC cells following exposure to PCAE was assessed by an MTT assay. DNA content and the induction of cell cycle apoptosis were analyzed by flow cytometry (FACS Calibur. Protein caspase-3 and, -9 as well as AIF were investigated using Western blot. Our results demonstrate growth inhibition of Ishikawa cells by PCAE. Furthermore, caspase-3 activity caused PCAE-treated cell lines to accumulate in apoptosis. Gene expression profiling (GEP results further suggest that, in addition to its known effects with regard to EC prevention, PCAE may also exert antitumor activity on established EC cells. Many previous studies have identified the chemo-preventive effects of natural plant materials and the potential role of these materials in chemotherapy. This current study used human EC Ishikawa cells to investigate the anti-tumor effects of PCAE in EC cells. Our results demonstrate that PCAE inhibits the growth of cancer cells and induces apoptosis, which suggests the potential applicability of PCAE as an antitumor agent.

  11. The Urtica dioica extract enhances sensitivity of paclitaxel drug to MDA-MB-468 breast cancer cells.

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    Mohammadi, Ali; Mansoori, Behzad; Aghapour, Mahyar; Shirjang, Solmaz; Nami, Sanam; Baradaran, Behzad

    2016-10-01

    Due to the chemo resistant nature of cancer cells and adverse effects of current therapies, researchers are looking for the most efficient therapeutic approach which has the lowest side effects and the highest toxicity on cancer cells. The aim of the present study was to investigate the synergic effect of Urtica dioica extract in combination with paclitaxel on cell death and invasion of human breast cancer MDA-MB-468 cell line. To determine the cytotoxic effects of Urtica dioica extract with paclitaxel, MTT assay was performed. The scratch test was exploited to assess the effects of Urtica dioica, Paclitaxel alone and combination on migration of cancer cells. The expression levels of snail-1, ZEB1, ZEB2, twist, Cdc2, cyclin B1 and Wee1 genes were quantified using qRT-PCR and western blot performed for snail-1expression. The effects of plant extract, Paclitaxel alone and combination on different phases of cell cycle was analyzed using flow cytometry. Results of MTT assay showed that Urtica dioica significantly destroyed cancer cells. Interestingly, Concurrent use of Urtica dioica extract with paclitaxel resulted in decreased IC50 dose of paclitaxel. Moreover, findings of scratch assay exhibited the inhibitory effects of Urtica dioica, Paclitaxel alone and combination on migration of MDA-MB-468 cell line. Our findings also demonstrated that the extract substantially decreased the Snail-1 and related gene expression. Ultimately, Cell cycle arrest occurred at G2/M phase post-treatment by deregulating Cdc2 and wee1. Our results demonstrated that the dichloromethane extract of Urtica dioica inhibit cell growth and migration. Also, Urtica dioica extract substantially increased sensitivity of breast cancer cells to paclitaxel. Therefore, it can be used as a potential candidate for treatment of breast cancer with paclitaxel. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. Cytotoxic and Apoptotic Activities of Prunus spinosa Trigno Ecotype Extract on Human Cancer Cells

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    Stefania Meschini

    2017-09-01

    Full Text Available The aim of this work was to demonstrate that a natural compound, not-toxic to normal cells, has cytotoxic and sensitizing effects on carcinoma cells, with the final goal of combining it with chemotherapeutic drugs to reduce the overall dose. Prunus spinosa Trigno ecotype (PsT drupe extract with a nutraceutical activator complex (NAC made of amino acids, vitamins and mineral salt blends, has shown in vitro anticancer activity. The cytotoxic effect of (PsT + NAC® has been evaluated on human cancer cells, with an initial screening with colorectal, uterine cervical, and bronchoalveolar cells, and a subsequent focus on colon carcinoma cells HCT116 and SW480. The viability reduction of HCT116 and SW480 after treatment with (PsT 10 mg/mL + NAC® was about 40% (p < 0.05, compared to control cells. The cell’s survival reduction was ineffective when the drug vehicle (NAC was replaced with a phosphate buffer saline (PBS or physiological solution (PS. The flow cytometry evaluation of cancer cells’ mitochondrial membrane potential showed an increase of 20% depolarized mitochondria. Cell cycle analysis showed a sub G1 (Gap 1 phase peak appearance (HCT116: 35.1%; SW480: 11.6%, indicating apoptotic cell death induction that was confirmed by Annexin V assay (HCT116: 86%; SW480: 96%. Normal cells were not altered by (PsT + NAC® treatments.

  13. Apoptosis Induction by Ocimum sanctum Extract in LNCaP Prostate Cancer Cells.

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    Dhandayuthapani, Sivanesan; Azad, Hasan; Rathinavelu, Appu

    2015-07-01

    Tulsi (Ocimum sanctum Linn), commonly known as "holy basil," has been used for the treatment of a wide range of ailments in many parts of the world. This study focuses on apoptosis-inducing ability of tulsi extract on prostate cancer cells. For this purpose LNCaP prostate cancer cells were treated with different concentrations of 70% ethanolic extract of tulsi (EET) and then the cytotoxicity was determined after 24 and 48 h. After treatment with EET externalization of phosphatidyl serine (PS) from the inner membrane to outer leaflet of the plasma membrane was clearly evidenced by the results obtained from both flow cytometry analysis with Annexin V-FITC and pSIVA-IANBD binding fluorescence microscopy assay. Depolarization of the mitochondrial membrane potential was also evidenced by the presence of 5,5',6,6'-tetrachlolo-1,1',3,3'-tetraethyl benzimedazolyl carbocyanine iodide (JC-1) monomeric form in the EET-treated cells that emitted the green fluorescence when compared with the control cells that emitted the red fluorescence due to aggregation of JC-1. Furthermore, the level of poly (ADP-ribose) polymerase (PARP) cleavage and Bcl-2 were determined using western blot analysis. When compared to the control cells the level of cleaved PARP was found to be higher with a concomitant decrease in the Bcl-2 level after 24 h of treatment of cells with EET. In addition, treatment with EET significantly elevated the activities of caspase-9 and caspase-3 in LNCaP cells compared with the control. Also, after 48 h of treatment all doses used in this study showed clear fragments of DNA, which is one of the hallmarks of apoptosis. Taken together, our findings suggest that, EET can effectively induce apoptosis in LNCaP cells via activation of caspase-9 and caspase-3 that can eventually lead to DNA fragmentation and cell death.

  14. Effects of tanshinone nanoemulsion and extract on inhibition of lung cancer cells A549

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    Lee, W. D.; Liang, Y. J.; Chen, B. H.

    2016-12-01

    Danshen (Salvia miltiorrhiza), a Chinese medicinal herb, consists of several functional components including tanshinones responsible for prevention of several chronic diseases. This study intends to prepare tanshinone extract and nanoemulsion from danshen and determine their inhibition effect on lung cancer cells A549. A highly stable tanshinone nanoemulsion composed of Capryol 90, Tween 80, ethanol and deionized water with the mean particle size of 14.2 nm was successfully prepared. Tanshinone nanoemulsion was found to be more effective in inhibiting A549 proliferation than tanshinone extract. Both nanoemulsion and extract could penetrate into cytoplasm through endocytosis, with the former being more susceptible than the latter. A dose-dependent response in up-regulation of p-JNK, p53 and p21 and down-regulation of CDK2, cyclin D1 and cyclin E1 expressions was observed with the cell cycle arrested at G0/G1 phase. The cellular microcompartment change of A549 was also investigated. The study demonstrated that tanshinone nanoemulsion may be used as a botanic drug for treatment of lung cancer.

  15. Anacyclus Pyrethrum Extract Exerts Anticancer Activities on the Human Colorectal Cancer Cell Line (HCT) by Targeting Apoptosis, Metastasis and Cell Cycle Arrest.

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    Mohammadi, Ali; Mansoori, Behzad; Baradaran, Pooneh Chokhachi; Baradaran, Sepideh Chokhachi; Baradaran, Behzad

    2017-12-01

    Colorectal cancer is the second leading cause of cancer mortality in the USA. There are a number of medicinal plants triggering apoptosis response in cancer cells, thus have a therapeutic potential. On the other hand, due to traditional uses and availability of Anacyclus pyrethrum extract, we decided to evaluate the efficacy of this medicinal herb on human colorectal cancer cell line (HCT). In the present study, the cytotoxic effects of Anacyclus pyrethrum extract were assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, and trypan blue viability dye. Then, flow cytometry assay was exploited to measure cell death and apoptosis stage. The scratch test was exploited to assess the effect of Anacyclus pyrethrum on the migration of cancer cells. The expression levels of Caspase 3, Bcl-2, MMP1, and Vimentin genes were quantified by real-time PCR. Finally, cell cycle was analyzed by flow cytometry. MTT assay showed that Anacyclus pyrethrum extract significantly inhibited the cell growth. According to the flow cytometry assay result, the herbal extract was able to induce apoptosis in colorectal cancer cells. Our findings also demonstrated that the plant extract substantially increases the caspase 3 mRNA expression, while decreases Bcl-2, MMP1, and Vimentin. Cell cycle arrest occurred in G1 stage, due to the results of flow cytometry. These results indicate that Anacyclus pyrethrum extract can successfully induce apoptosis in HCT cells. Therefore, it could be used as a novel therapeutic candidate for colorectal cancer treatment.

  16. The antiproliferative effect of Moringa oleifera crude aqueous leaf extract on cancerous human alveolar epithelial cells.

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    Tiloke, Charlette; Phulukdaree, Alisa; Chuturgoon, Anil A

    2013-09-16

    The incidence of lung cancer is expected to increase due to increases in exposure to airborne pollutants and cigarette smoke. Moringa oleifera (MO), a medicinal plant found mainly in Asia and South Africa is used in the traditional treatment of various ailments including cancer. This study investigated the antiproliferative effect of MO leaf extract (MOE) in cancerous A549 lung cells. A crude aqueous leaf extract was prepared and the cells were treated with 166.7 μg/ml MOE (IC50) for 24 h and assayed for oxidative stress (TBARS and Glutathione assays), DNA fragmentation (comet assay) and caspase (3/7 and 9) activity. In addition, the expression of Nrf2, p53, Smac/DIABLO and PARP-1 was determined by Western blotting. The mRNA expression of Nrf2 and p53 was assessed using qPCR. A significant increase in reactive oxygen species with a concomitant decrease in intracellular glutathione levels (p < 0.001) in MOE treated A549 cells was observed. MOE showed a significant reduction in Nrf2 protein expression (1.89-fold, p < 0.05) and mRNA expression (1.44-fold). A higher level of DNA fragmentation (p < 0.0001) was seen in the MOE treated cells. MOE's pro-apoptotic action was confirmed by the significant increase in p53 protein expression (1.02-fold, p < 0.05), p53 mRNA expression (1.59-fold), caspase-9 (1.28-fold, p < 0.05), caspase-3/7 (1.52-fold) activities and an enhanced expression of Smac/DIABLO. MOE also caused the cleavage and activation of PARP-1 into 89 KDa and 24 KDa fragments (p < 0.0001). MOE exerts antiproliferative effects in A549 lung cells by increasing oxidative stress, DNA fragmentation and inducing apoptosis.

  17. Anticancer effect of ethanol Lycium barbarum (Goji berry) extract on human breast cancer T47D cell line.

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    Wawruszak, Anna; Czerwonka, Arkadiusz; Okła, Karolina; Rzeski, Wojciech

    2016-09-01

    The anticancer activity of ethanol extract isolated from Goji berry (EEGB) on T47D human breast cancer cell line has been reported. Cell viability and cell proliferation were examined with the use of BrdU, MTT and NR methods. Induction of apoptosis was assessed by propidium iodide and Hoechst 33342 staining. Expression of genes involved in cell proliferation, apoptosis, cell cycle control and regulation of transcription was estimated using Western blotting analysis. EEGB inhibited the proliferation of breast cancer cells in a time-, and dose-dependent manner. The study confirmed the lack of EEGB cytotoxic activity to normal human skin fibroblasts. Western blot analysis demonstrated an increase in pro-apoptotic and a decrease in anti-apoptotic proteins' expression in cells treated with the extract. Anticancer activity and lack of toxicity against normal cells indicate a chemopreventive potential of Goji berries in breast cancer treatment.

  18. Effect of crude saponins from Gaultheria trichophylla extract on growth inhibition in human colorectal cancer cells

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    Fiaz Alam

    2015-03-01

    Full Text Available The genus Gaultheria also comprised of species with reported cytotoxic activities. Current research work was carried out to evaluate G. trichophylla crude extract and respective saponins fraction against human colorectal cancer cell line (Caco-2 based on cell viability assays. Caco-2 cells treated with the crude extract showed significant growth inhibition (p< 0.001 in a dose dependent manner with apparent IC50 value of 200 μg/mL and 100 μg/mL in MTT and NRU assays respectively. The fractioned crude saponins showed an enhanced response and inhibited the growth of Caco-2 by 93.6 and 97.4% in MTT and NRU assays respectively, with compared to actinomycin-D (65%. The DAPI staining of cell treated with crude saponins observed under confocal microscope showed shrunken nuclei with apparent nuclear fragmentation and chromatin condensation indicating apoptosis mode of cell death. The study exhibited that the G. Trichophylla saponins induced apoptosis of Caco-2 cell lines. This study provides new evidences to further explore this plant for the novel targets in anticancer drug development.

  19. The dual effects of polar methanolic extract of Hypericum perforatum L. in bladder cancer cells

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    Nseyo, U. O.; Nseyo, O. U.; Shiverick, K. T.; Medrano, T.; Mejia, M.; Stavropoulos, N.; Tsimaris, I.; Skalkos, D.

    2007-02-01

    Introduction and background: We have reported on the polar methanolic fraction (PMF) of Hypericum Perforatum L as a novel photosensitizing agent for photodynamic therapy (PDT) and photodynamic diagnosis (PDD). PMF has been tested in human leukemic cells, HL-60 cells, cord blood hemopoietic progenitor cells, bladder cancers derived from metastatic lymph node (T-24) and primary papillary bladder lesion (RT-4). However, the mechanisms of the effects of PMF on these human cell lines have not been elucidated. We have investigated mechanisms of PMF + light versus PMF-alone (dark experiment) in T-24 human bladder cancer cells. Methods: PMF was prepared from an aerial herb of HPL which was brewed in methanol and extracted with ether and methanol. Stock solutions of PMF were made in DSMO and stored in dark conditions. PMF contains 0.57% hypericin and 2.52% hyperforin. The T24 cell line was obtained from American Type Culture Collection (ATCC). In PDT treatment, PMF (60μg/ml) was incubated with cells, which were excited with laser light (630nm) 24 hours later. Apoptosis was determined by DNA fragmentation/laddering assay. DNA isolation was performed according to the manufacture's instructions with the Kit (Oncogene Kit#AM41). Isolated DNA samples were separated by electrophoresis in 1.5% in agarose gels and bands were visualized by ethidium bromide labeling. The initial cell cycle analysis and phase distribution was by flow cytometry. DNA synthesis was measured by [3H] thymidine incorporation, and cell cycle regulatory proteins were assayed by Western immunoblot. Results: The results of the flow cytometry showed PMF +light induced significant (40%) apoptosis in T24 cells, whereas Light or PMF alone produced little apoptosis. The percentage of cells in G 0/G I phase was decreased by 25% and in G2/M phase by 38%. The main impact was observed on the S phase which was blocked by 78% from the specific photocytotoxic process. DNA laddering analysis showed that PMF (60

  20. The Key Role of Mitochondrial Apoptotic Pathway in the Cytotoxic Effect of Mushroom Extracts on Cancer Cells.

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    Han, Mei; Ling, Ming-Tat; Chen, Jiezhong

    2015-01-01

    Mushroom extracts have been extensively studied for their medicinal effects. They can stimulate immune responses and thus have been explored in cancer treatment. Recently, it has also been shown that some mushroom extracts can produce direct cytotoxic effect on cancer cells. In this review, we summarize the cytotoxic effect of mushroom extracts in cancer treatment revealed by both in vitro and in vivo studies. We also summarize the current understanding of the mechanisms associated with such an effect with an emphasis on the mitochondrial apoptotic pathway. The recent finding that mushroom extracts have direct cytotoxic effects supplements their known immune stimulating effects. Thus, novel anticancer agents based on new findings from mushroom extracts may soon be added to the present pool of anticancer drugs. Specifically, we propose that nanodelivery of the bioactive compounds of mushroom extracts to mitochondria will further increase their potential treatment efficacy.

  1. Anti-carcinogenic and anti-angiogenic properties of the extracts of Acorus calamus on gastric cancer cells

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    Samaneh Rahamoz Haghighi

    2017-02-01

    Full Text Available Objective: Acorus calamus (A. calamus has been used as a medicinal plant in Asia for its effects on digestive system for the last 2000 years. To investigate the anti-cancer activity of rhizome of A. calamus, the ethanolic and methanolic extracts and essential oil of the rhizome were prepared and their effects were assessed on human gastric cancer cell line (AGS. Materials and Methods: The viability of cells which were treated with the extracts and the essential oil was assessed by MTT assay. To evaluate the anti-angiogenic property of the extracts, in vitro tube formation assay was done. Cell cycle distribution and the expression of Oct4 and Nucleostemin, after treatments, were checked by flowcytometry and quantitative RT-PCR, respectively. Furthermore, analysis of essential oil from A.calamus was done by GC-MS. Results: Our results showed that the growth of AGS cells was inhibited by the extracts and essential oil and the extracts inhibited the angiogenesis in HUVEC cells. Our data revealed that the extracts and essential oil of A. calamus caused G1 arrest in AGS cells and downregulation of Oct4 and NS after treatment. By GC-MS analysis, we found new compoundssuch as epiprezizaene, valencene and isocyclocitral in essential oil of A. Conclusions: All together, our results showed that the extracts of A. calamus have anti-proliferative and anti-angiogenic effects on cancer cells.

  2. Effects of Calophyllum inophyllum fruit extract on the proliferation and morphological characteristics of human breast cancer cells MCF-7

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    Shanmugapriya

    2016-04-01

    Full Text Available Objective: To evaluate the antiproliferative activity of Calophyllum inophyllum (C. inophyllum fruit extract against human breast cancer cells MCF-7. Methods: The cytotoxic effect of C. inophyllum fruit extract against MCF-7 cancer cells was evaluated through MTT and CyQuant assays for 24 h and the morphological investigation of treated MCF-7 cells was observed under optical microscope using Giemsa staining. Results: The cytotoxic effect of C. inophyllum fruit extract against MCF-7 cancer cells was evaluated through MTT and CyQuant assays simultaneously for 24 h after treatment, which demonstrated the inhibition of cell viability with the IC50 values of 19.63 µg/mL and 27.54 µg/mL, respectively. The preliminary time-based morphological investigation of MCF-7 cells treated with the IC 50 value (23.59 µg/mL of C. inophyllum fruit extract was observed under an optical microscopy via Giemsa staining, which exhibited prominent histological characteristics of apoptosis. Conclusions: This study clearly proved that the proliferation of human breast cancer cell MCF-7 was inhibited by C. inophyllum fruit extract resulted from the induction of apoptosis in MCF-7 cells.

  3. Antioxidant activity and growth inhibition of human colon cancer cells by crude and purified fucoidan preparations extracted from Sargassum cristaefolium

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    Cheng-Yuan Wang

    2015-12-01

    Full Text Available Fucose-containing sulfated polysaccharides, also termed “fucoidans”, which are known to possess antioxidant, anticoagulant, anticancer, antiviral, and immunomodulating properties, are normally isolated from brown algae via various extraction techniques. In the present study, two methods (SC1 and SC2 for isolation of fucoidan from Sargassum cristaefolium were compared, with regard to the extraction yields, antioxidant activity, and inhibition of growth of human colon cancer cells exhibited by the respective extracts. SC1 and SC2 differ in the number of extraction steps and concentration of ethanol used, as well as the obtained sulfated polysaccharide extracts, namely, crude fucoidan preparation (CFP and purified fucoidan preparation (PFP, respectively. Thin layer chromatography, Fourier transform infrared analysis, and measurements of fucose and sulfate contents revealed that the extracts were fucoidan. There was a higher extraction yield for CFP, which contained less fucose and sulfate but more uronic acid, and had weaker antioxidant activity and inhibition of growth in human colon cancer cells. In contrast, there was a lower extraction yield for PFP, which contained more fucose and sulfate but less uronic acid, and had stronger antioxidant activity and inhibition of growth in human colon cancer cells. Thus, since the difference in bioactive activities between CFP and PFP was not remarkable, the high extraction yield of SC1 might be favored as a method in industrial usage for extracting fucoidan.

  4. Differential effects of Viscum album extract IscadorQu on cell cycle progression and apoptosis in cancer cells.

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    Harmsma, Marjan; Grommé, Monique; Ummelen, Monique; Dignef, Wendy; Tusenius, Karel Jan; Ramaekers, Frans C S

    2004-12-01

    Extracts from European mistletoe or Viscum album L. have been reported to exert cytotoxic and immunomodulatory effects in vitro and in vivo. The mechanism of this anti-tumoral activity is however, largely unknown. In this study we tested the hypothesis that IscadorQu, an aqueous fermented extract from the European mistletoe grown on oaks, induces tumor regression by cell cycle inhibition and/or interference with apoptotic signaling pathways in cancer cells. Also a possible effect on angiogenesis, which is a prerequisite for tumor growth in vivo, is studied in endothelial cell cultures. Furthermore, we examined which apoptotic signaling route is activated by staining cells for specific pro-apoptotic proteins. To characterize these properties, 6 different human cancer cell lines, one epidermis derived cell line and 2 endothelial cell cultures were incubated with different concentrations of IscadorQu. Cell cycle kinetics parameters were measured by bromodeoxyuridine (BrdU) pulse labeling and tubulin staining. Apoptotic responses were detected by M30 CytoDeath or Annexin V/propidium iodide assays. Characterization of the apoptotic pathway was performed by staining cells for active caspase 3, active caspase 8, cytochrome C and chloromethyl-X-rosamine. The results of this study show that sensitivity to IscadorQu treatment varies strongly between different cell lines. In sensitive cell lines, including tumor and endothelial cell cultures, IscadorQu caused early cell cycle inhibition followed by apoptosis in a dose-dependent manner. Apoptosis was induced by activating the mitochondrial but not the death receptor-dependent pathway.

  5. Cytotoxic effects of solvent-extracted active components of Salvia miltiorrhiza Bunge on human cancer cell lines.

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    Sung, Bokyung; Chung, Hye Sun; Kim, Minjung; Kang, Yong Jung; Kim, Dong Hwan; Hwang, Seong Yeon; Kim, Min Jo; Kim, Cheol Min; Chung, Hae Young; Kim, Nam Deuk

    2015-04-01

    Herbal extracts and dietary supplements may be extracted from the medicinal plants used in traditional Chinese medicine, and are used increasingly commonly worldwide for their benefits to health and quality of life. Thus, ensuring that they are safe for human consumption is a critical issue for the preparation of plant extracts as dietary supplements. The present study investigated extracts of Salvia miltiorrhiza Bunge (S. miltiorrhiza), traditionally used in Asian countries to treat a variety of conditions, as a dietary supplement or as an ingredient in functional foods. Dried S. miltiorrhiza root was extracted with various solvents and under varying extraction conditions, and the effects of the extracts on the viability of five human cancer cell lines were compared. Extracts obtained using 100% ethanol and 100% acetone as solvents exhibited more potent effects compared with extracts obtained using 70 and 30% aqueous ethanol. Furthermore, the active components of S. miltiorrhiza ethanol extracts, known as tanshinones, were investigated. Dihydrotanshinone I was observed to exhibit a higher cytotoxic potential compared with the other tanshinones in the majority of the examined cell lines. Conversely, cryptotanshinone exhibited weak anti-cancer activity. In summary, the results of the present study suggest that the active components obtained from an ethanol extract of S. miltiorrhiza possess the potential to be used as ingredients in functional and health care foods that may be used to improve the effectiveness of chemotherapeutics in the prevention and/or treatment of cancer.

  6. Grape seed extracts modify the outcome of oxaliplatin in colon cancer cells by interfering with cellular mechanisms of drug cytotoxicity.

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    Porcelli, Letizia; Iacobazzi, Rosa Maria; Quatrale, Anna Elisa; Bergamini, Carlo; Denora, Nunzio; Crupi, Pasquale; Antonacci, Donato; Mangia, Anita; Simone, Giovanni; Silvestris, Nicola; Azzariti, Amalia

    2017-08-01

    Grape seed extracts are commonly utilized as dietary supplements for their antioxidant properties, even from cancer patients. However, whether these natural extracts interfere with chemotherapeutics utilized in colon cancer treatment is still poorly investigated. The cytotoxicity of extracts from Italia and Palieri cultivars either alone or in combination with oxaliplatin was evaluated in colon cancer cells. Grape seed extracts displayed anti-proliferative activity depending on the concentration utilized through apoptosis induction. In combination, they affected the activation of Erk1/2 and counteracted the intrinsic and the extrinsic pathway of apoptosis, the DNA damage and the generation of ROS induced by oxaliplatin. Noteworthy grape seed extracts strongly enhanced the uptake of oxaliplatin into all cells, by affecting the cell transport system of platinum. The addition of these natural extracts to oxaliplatin strongly reduced the cellular response to oxaliplatin and allowed a huge accumulation of platinum into cells. Here, we shed light on the chemical biology underlying the combination of grape seed extracts and oxaliplatin, demonstrating that they might be detrimental to oxaliplatin effectiveness in colon cancer therapy.

  7. Antiproliferative and apoptotic effect of Morus nigra extract on human prostate cancer cells

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    Ibrahim Turan

    2017-02-01

    Full Text Available Background: Morus nigra L. belongs to the family Moraceae and is frequently used in traditional medicine. Numerous studies have investigated the antiproliferative effects of various extracts of different Morus species, but studies involving the in vitro cytotoxic effect of M. nigra extract are very limited. The purpose of this study was to evaluate the phenolic composition and antioxidant activity of dimethyl sulfoxide extract of M. nigra (DEM and to investigate, for the first time, the probable cytotoxic effect in human prostate adenocarcinoma (PC-3 cells together with the mechanism involved. Methods: Total polyphenolic contents (TPC, ferric reducing antioxidant power (FRAP and phenolic compounds of DEM were evaluated using spectrophotometric procedures and HPLC. The cytotoxic effect of DEM on PC-3 cells was revealed using the MTT assay. Mechanisms involved in the cytotoxic effect of DEM on PC-3 cells were then investigated in terms of apoptosis, mitochondrial membrane potential and cell cycle using flow cytometry, while caspase activity was investigated using luminometric analysis. Results: TPC and FRAP values were 20.7 ± 0.3 mg gallic acid equivalents and 48.8 ± 1.6 mg trolox equivalents per g sample, respectively. Ascorbic acid and chlorogenic acid were the major phenolic compounds detected at HPLC analysis. DEM arrested the cell cycle of PC-3 cells at the G1 phase, induced apoptosis via increased caspase activity and reduced mitochondrial membrane potential. Conclusions: Our results indicate that M. nigra may be a novel candidate for the development of new natural product based therapeutic agents against prostate cancer.

  8. The Antiproliferative Effect of Moringa oleifera Crude Aqueous Leaf Extract on Human Esophageal Cancer Cells.

    Science.gov (United States)

    Tiloke, Charlette; Phulukdaree, Alisa; Chuturgoon, Anil A

    2016-04-01

    Esophageal cancer (EC) is commonly diagnosed in South Africa (SA), with high incidences occurring in SA's black population. Moringa oleifera (MO), a multipurpose tree, is used traditionally for its nutritional and medicinal properties. It has been used for the treatment of a variety of ailments, including cancer. We investigated the antiproliferative effect of MO crude aqueous leaf extract (MOE) on a cancerous esophageal cell line (SNO). SNO cells were exposed to a range of MOE dilutions to evaluate cytotoxicity (MTT assay). Oxidative stress was determined using the TBARS assay. The comet assay was used to assess DNA damage. We then determined cell death mechanisms by measuring phosphatidylserine (PS) externalization (flow cytometry), caspase-3/7 and caspase-9 activities, and adenosine triphosphate (ATP) levels (luminometry). Protein expression of Smac/DIABLO and PARP-1 was determined by western blotting. SNO cells were treated with a range of MOE dilutions to obtain an IC50 value of 389.2 μg/mL MOE (24 h), which was used in all subsequent assays. MOE significantly increased lipid peroxidation (P < .05) and DNA fragmentation (P < .0001) in SNO cells. The induction of apoptosis was confirmed by the increase in PS externalization (P < .0001), caspase-9 (P < .05) and caspase-3/7 (P = .22) activities, and decreased ATP levels (P < .0001). MOE significantly increased both the expression of Smac/DIABLO protein and cleavage of PARP-1, resulting in an increase in the 24-kDa fragment (P < .001). MOE possesses antiproliferative effects on SNO EC cells by increasing lipid peroxidation, DNA fragmentation, and induction of apoptosis.

  9. Induction of Mitochondria Mediated Apoptosis in Human Breast Cancer Cells (T-47D) by Annona reticulata L. Leaves Methanolic Extracts.

    Science.gov (United States)

    Roham, Pratiksha H; Kharat, Kiran R; Mungde, Priyanka; Jadhav, Mahadev A; Makhija, Surinder J

    2016-01-01

    Annona reticulata Linn. (Common name: Bullock's-heart) (Annonaceae family) is a semi-evergreen and small deciduous tree. The extracts of various parts of Annona reticulata L. have been reported as cytotoxic to many cancer cells. Annona reticulata L. leaves' methanolic extract (ARME) was prepared and used against the breast cancer cells. The breast cancer cells (T-47D) viability and IC50 were evaluated by Vybrant® MTT Cell Proliferation Assay Kit. Detection of phosphatidylserine on membranes of apoptotic cells was done by Attune flow cytometer. RNA transcripts were quantified in ARME treated and untreated cells. Finally, the Vybrant® FAM Poly Caspases assay kit was used for analysis of polycaspases activity in T-47D cells. The IC50 (5 ± 0.5 µg/mL) of the ARME was found against breast cancer cells (T-47D). The Paclitaxel was used as a control standard drug for the study. The downregulation of Bcl-2 and upregulation of Bax and Bak, and caspases activation suggested induction of apoptosis in T-47D cells by ARME through mitochondrial pathway. The cell cycle halted at G2/M phase in the ARME treated cells. The ARME was found to be effective against Breast cancer cells (T-47D).

  10. The Value of Caspase-3 after the Application of Annona muricata Leaf Extract in COLO-205 Colorectal Cancer Cell Line

    Science.gov (United States)

    Syam, Ari Fahrial; Meilany, Sofy; Laksono, Bayu; Prabu, Oryza Gryagus; Bekti, Heri Setiyo; Indrawati, Lili; Makmun, Dadang

    2017-01-01

    Annona muricata, commonly known as soursop, contains annonacin, acetogenin, and polyphenol which are known to have chemopreventive effects on cancer. In this study, we tend to evaluate the apoptosis-inducing effect of soursop (Annona muricata) leaf extract on the colorectal cancer cell line COLO-205 through the activities of caspase-3 which is a marker of cell apoptosis. Cell cultures were incubated with soursop leaf with a concentration of 10 μg/ml and then compared with those of the incubated positive control leucovorin 10 μg/ml and placebo as a negative control. The apoptotic activity of caspase-3 was measured with ELISA. After the administration of each treatment in the colorectal cancer cell line COLO-205, the expression of caspase-3 activity was 1422 ng/ml after incubation with the extract of Annona muricata leaves, 1373 ng/ml after the administration of leucovorin, and 1297 ng/ml in the one with placebo. Annona muricata leaf extract elevated caspase-3 by 1.09 times compared to that of the pure cell line. Annona muricata leaf extract had a higher value of caspase-3 activity than leucovorin and placebo in the COLO-205 colorectal cancer cell line. These results may suggest that Annona muricata leaf extract had anticancer properties by enhancing caspase-3 activity which is a proapoptotic marker. PMID:28487731

  11. The Value of Caspase-3 after the Application of Annona muricata Leaf Extract in COLO-205 Colorectal Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    Murdani Abdullah

    2017-01-01

    Full Text Available Annona muricata, commonly known as soursop, contains annonacin, acetogenin, and polyphenol which are known to have chemopreventive effects on cancer. In this study, we tend to evaluate the apoptosis-inducing effect of soursop (Annona muricata leaf extract on the colorectal cancer cell line COLO-205 through the activities of caspase-3 which is a marker of cell apoptosis. Cell cultures were incubated with soursop leaf with a concentration of 10 μg/ml and then compared with those of the incubated positive control leucovorin 10 μg/ml and placebo as a negative control. The apoptotic activity of caspase-3 was measured with ELISA. After the administration of each treatment in the colorectal cancer cell line COLO-205, the expression of caspase-3 activity was 1422 ng/ml after incubation with the extract of Annona muricata leaves, 1373 ng/ml after the administration of leucovorin, and 1297 ng/ml in the one with placebo. Annona muricata leaf extract elevated caspase-3 by 1.09 times compared to that of the pure cell line. Annona muricata leaf extract had a higher value of caspase-3 activity than leucovorin and placebo in the COLO-205 colorectal cancer cell line. These results may suggest that Annona muricata leaf extract had anticancer properties by enhancing caspase-3 activity which is a proapoptotic marker.

  12. American cranberry (Vaccinium macrocarpon) extract affects human prostate cancer cell growth via cell cycle arrest by modulating expression of cell cycle regulators.

    Science.gov (United States)

    Déziel, Bob; MacPhee, James; Patel, Kunal; Catalli, Adriana; Kulka, Marianna; Neto, Catherine; Gottschall-Pass, Katherine; Hurta, Robert

    2012-05-01

    Prostate cancer is one of the most common cancers in the world, and its prevalence is expected to increase appreciably in the coming decades. As such, more research is necessary to understand the etiology, progression and possible preventative measures to delay or to stop the development of this disease. Recently, there has been interest in examining the effects of whole extracts from commonly harvested crops on the behaviour and progression of cancer. Here, we describe the effects of whole cranberry extract (WCE) on the behaviour of DU145 human prostate cancer cells in vitro. Following treatment of DU145 human prostate cancer cells with 10, 25 and 50 μg ml⁻¹ of WCE, respectively for 6 h, WCE significantly decreased the cellular viability of DU145 cells. WCE also decreased the proportion of cells in the G2-M phase of the cell cycle and increased the proportion of cells in the G1 phase of the cell cycle following treatment of cells with 25 and 50 μg ml⁻¹ treatment of WCE for 6 h. These alterations in cell cycle were associated with changes in cell cycle regulatory proteins and other cell cycle associated proteins. WCE decreased the expression of CDK4, cyclin A, cyclin B1, cyclin D1 and cyclin E, and increased the expression of p27. Changes in p16(INK4a) and pRBp107 protein expression levels also were evident, however, the changes noted in p16(INK4a) and pRBp107 protein expression levels were not statistically significant. These findings demonstrate that phytochemical extracts from the American cranberry (Vaccinium macrocarpon) can affect the behaviour of human prostate cancer cells in vitro and further support the potential health benefits associated with cranberries.

  13. Evaluation of aqueous extracts of Taraxacum officinale on growth and invasion of breast and prostate cancer cells.

    Science.gov (United States)

    Sigstedt, Sophia C; Hooten, Carla J; Callewaert, Manika C; Jenkins, Aaron R; Romero, Anntherese E; Pullin, Michael J; Kornienko, Alexander; Lowrey, Timothy K; Slambrouck, Severine Van; Steelant, Wim F A

    2008-05-01

    Ethnotraditional use of plant-derived natural products plays a significant role in the discovery and development of potential medicinal agents. Plants of the genus Taraxacum, commonly known as dandelions, have a history of use in Chinese, Arabian and Native American traditional medicine, to treat a variety of diseases including cancer. To date, however, very few studies have been reported on the anti-carcinogenic activity of Taraxacum officinale (TO). In the present study, three aqueous extracts were prepared from the mature leaves, flowers and roots, and investigated on tumor progression related processes such as proliferation and invasion. Our results show that the crude extract of dandelion leaf (DLE) decreased the growth of MCF-7/AZ breast cancer cells in an ERK-dependent manner, whereas the aqueous extracts of dandelion flower (DFE) and root (DRE) had no effect on the growth of either cell line. Furthermore, DRE was found to block invasion of MCF-7/AZ breast cancer cells while DLE blocked the invasion of LNCaP prostate cancer cells, into collagen type I. Inhibition of invasion was further evidenced by decreased phosphorylation levels of FAK and src as well as reduced activities of matrix metalloproteinases, MMP-2 and MMP-9. This study provides new scientific data on TO and suggests that TO extracts or individual components present in the extracts may be of value as novel anti-cancer agents.

  14. Pinus radiata bark extract induces caspase-independent apoptosis-like cell death in MCF-7 human breast cancer cells.

    Science.gov (United States)

    Venkatesan, Thamizhiniyan; Choi, Young-Woong; Mun, Sung-Phil; Kim, Young-Kyoon

    2016-10-01

    In the present study, we investigated the anticancer activity of Pinus radiata bark extract (PRE) against MCF-7 human breast cancer cells. First, we observed that PRE induces potent cytotoxic effects in MCF-7 cells. The cell death had features of cytoplasmic vacuolation, plasma membrane permeabilization, chromatin condensation, phosphatidylserine externalization, absence of executioner caspase activation, insensitivity to z-VAD-fmk (caspase inhibitor), increased accumulation of autophagic markers, and lysosomal membrane permeabilization (LMP). Both the inhibition of early stage autophagy flux and lysosomal cathepsins did not improve cell viability. The antioxidant, n-acetylcysteine, and the iron chelator, deferoxamine, failed to restore the lysosomal integrity indicating that PRE-induced LMP is independent of oxidative stress. This was corroborated with the absence of enhanced ROS production in PRE-treated cells. Chelation of both intracellular calcium and zinc promotes PRE-induced LMP. Geranylgeranylacetone, an inducer of Hsp70 expression, also had no significant protective effect on PRE-induced LMP. Moreover, we found that PRE induces endoplasmic reticulum (ER) stress and mitochondrial membrane depolarization in MCF-7 cells. The ER stress inhibitor, 4-PBA, did not restore the mitochondrial membrane integrity, whereas cathepsin inhibitors demonstrated significant protective effects. Collectively, our results suggest that PRE induces an autophagic block, LMP, ER stress, and mitochondrial dysfunction in MCF-7 cells. However, further studies are clearly warranted to explore the exact mechanism behind the anticancer activity of PRE in MCF-7 human breast cancer cells.

  15. Apoptosis induction by Pleurotus sajor-caju (Fr.) Singer extracts on colorectal cancer cell lines.

    Science.gov (United States)

    Finimundy, Tiane C; Abreu, Rui M V; Bonetto, Natalia; Scariot, Fernando J; Dillon, Aldo J P; Echeverrigaray, Sergio; Barros, Lillian; Ferreira, Isabel C F R; Henriques, João A P; Roesch-Ely, Mariana

    2018-02-01

    Pleurotus sajor-caju (PSC) is an edible mushroom used in food supplements, presenting antitumor properties through induction of cell death pathways. The PSC potential against colorectal cancer was analyzed by exposing HCT116 wt cells to different PSC extracts. The PSC n-hexane extract (PSC-hex) showed the highest cytotoxicity effect (IC 50 value 0.05 mg/mL). The observed cytotoxicity was then associated to apoptosis-promoting and cell cycle-arrest pathways. PSC-hex was able to induce apoptosis related to breakdown of mitochondrial membrane potential and ROS generation. The absence of cytotoxicity in HTC116 -p53 and HTC116 -Bax cells, alongside with an increase in p53, Bax and Caspase-3 expression, and decrease in Bcl-2 expression, supports that the pro-apoptotic effect is probably induced through a p53 associated pathway. PSC-hex induced cell cycle arrest at G2/M in HCT116 wt without cytotoxicity in HTC116 -p21  cells. These findings suggest that a p21/p53 cell cycle regulation pathway is probably disrupted by compounds present on PSC-hex. Identification of the major components was then performed with ergosta-5,7,22-trien-3β-ol representing 30.6% of total weight. In silico docking studies of ergosta-5,7,22-trien-3β against Bcl-2 were performed and results show a credible interaction with the Bcl-2 hydrophobic cleft. The results show that PSC-hex can be used as supplementary food for adjuvant therapy in colorectal carcinoma. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Bioactivity of the Murex Homeopathic Remedy and of Extracts from an Australian Muricid Mollusc against Human Cancer Cells

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    Kirsten Benkendorff

    2011-01-01

    Full Text Available Marine molluscs from the family Muricidae are the source of a homeopathic remedy Murex, which is used to treat a range of conditions, including cancer. The aim of this study was to evaluate the in vitro bioactivity of egg mass extracts of the Australian muricid Dicathais orbita, in comparison to the Murex remedy, against human carcinoma and lymphoma cells. Liquid chromatography coupled with mass spectrometry (LC-MS was used to characterize the chemical composition of the extracts and homeopathic remedy, focusing on biologically active brominated indoles. The MTS (tetrazolium salt colorimetric assay was used to determine effects on cell viability, while necrosis and apoptosis induction were investigated using flow cytometry (propidium iodide and Annexin-V staining, resp.. Cells were treated with varying concentrations (1–0.01 mg/mL of crude and semi-purified extracts or preparations (dilute 1 M and concentrated 4 mg/mL from the Murex remedy (4 h. The Murex remedy showed little biological activity against the majority of cell lines tested. In contrast, the D. orbita egg extracts significantly decreased cell viability in the majority of carcinoma cell lines. Flow cytometry revealed these extracts induce necrosis in HT29 colorectal cancer cells, whereas apoptosis was induced in Jurkat cells. These findings highlight the biomedical potential of Muricidae extracts in the development of a natural therapy for the treatment of neoplastic tumors and lymphomas.

  17. Antiproliferative and Apoptotic Effects Triggered by Grape Seed Extract (GSE versus Epigallocatechin and Procyanidins on Colon Cancer Cell Lines

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    Simona Dinicola

    2012-01-01

    Full Text Available Grape seed extract has been proven to exert anticancer effects on different tumors. These effects are mainly ascribed to catechin and procyanidin content. Analytical studies demonstrated that grape seed extract composition is complex and it is likely other components could exert biological activities. Using cell count and flow cytometry assays, we evaluated the cytostatic and apoptotic effects produced by three different grape seed extracts from Italia, Palieri and Red Globe cultivars, on Caco2 and HCT-8 colon cancer cells. These effects were compared to those induced by epigallocatechin and procyanidins, alone or in association, on the same cell lines. All the extracts induced growth inhibition and apoptosis in Caco2 and HCT-8 cells, along the intrinsic apoptotic pathway. On both cell lines, growth inhibition induced by Italia and Palieri grape seed extracts was significantly higher than that it has been recorded with epigallocatechin, procyanidins and their association. In Caco2 cells, the extract from Red Globe cultivar was less effective in inducing growth inhibition than procyanidins alone and in association with epigallocatechin, whereas, in HCT-8 cells, only the association of epigallocatechin and procyanidins triggers a significant proliferation decrease. On both cell lines, apoptosis induced by Italia, Palieri and Red Globe grape seed extracts was considerably higher than has been recorded with epigallocatechin, procyanidins and their association. These data support the hypothesis by which other compounds, present in the grape seed extracts, are likely to enhance the anticancer effects.

  18. Antiproliferative and apoptotic effects triggered by Grape Seed Extract (GSE) versus epigallocatechin and procyanidins on colon cancer cell lines.

    Science.gov (United States)

    Dinicola, Simona; Cucina, Alessandra; Pasqualato, Alessia; D'Anselmi, Fabrizio; Proietti, Sara; Lisi, Elisabetta; Pasqua, Gabriella; Antonacci, Donato; Bizzarri, Mariano

    2012-01-01

    Grape seed extract has been proven to exert anticancer effects on different tumors. These effects are mainly ascribed to catechin and procyanidin content. Analytical studies demonstrated that grape seed extract composition is complex and it is likely other components could exert biological activities. Using cell count and flow cytometry assays, we evaluated the cytostatic and apoptotic effects produced by three different grape seed extracts from Italia, Palieri and Red Globe cultivars, on Caco2 and HCT-8 colon cancer cells. These effects were compared to those induced by epigallocatechin and procyanidins, alone or in association, on the same cell lines. All the extracts induced growth inhibition and apoptosis in Caco2 and HCT-8 cells, along the intrinsic apoptotic pathway. On both cell lines, growth inhibition induced by Italia and Palieri grape seed extracts was significantly higher than that it has been recorded with epigallocatechin, procyanidins and their association. In Caco2 cells, the extract from Red Globe cultivar was less effective in inducing growth inhibition than procyanidins alone and in association with epigallocatechin, whereas, in HCT-8 cells, only the association of epigallocatechin and procyanidins triggers a significant proliferation decrease. On both cell lines, apoptosis induced by Italia, Palieri and Red Globe grape seed extracts was considerably higher than has been recorded with epigallocatechin, procyanidins and their association. These data support the hypothesis by which other compounds, present in the grape seed extracts, are likely to enhance the anticancer effects.

  19. Crude aqueous extracts of Pluchea indica (L.) Less. inhibit proliferation and migration of cancer cells through induction of p53-dependent cell death

    Science.gov (United States)

    2012-01-01

    Background Pluchea indica (L.) Less. (Asteraceae) is a perennial shrub plant with anti-inflammatory and antioxidant medicinal properties. However, the anti-cancer properties of its aqueous extracts have not been studied. The aim of this study was to investigate the anti-proliferation, anti-migration, and pro-apoptotic properties of crude aqueous extracts of P. indica leaf and root on human malignant glioma cancer cells and human cervical cancer cells, and the underlying molecular mechanism. Methods GBM8401 human glioma cells and HeLa cervical carcinoma cells were treated with various concentrations of crude aqueous extracts of P. indica leaf and root and cancer cell proliferation and viability were measured by cell growth curves, trypan blue exclusions, and the tetrazolium reduction assay. Effects of the crude aqueous extracts on focus formation, migration, and apoptosis of cancer cells were studied as well. The molecular mechanism that contributed to the anti-cancer activities of crude aqueous extracts of P. indica root was also examined using Western blotting analysis. Results Crude aqueous extracts of P. indica leaf and root suppressed proliferation, viability, and migration of GBM8401 and HeLa cells. Treatment with crude aqueous extracts of P. indica leaf and root for 48 hours resulted in a significant 75% and 70% inhibition on proliferation and viability of GBM8401 and HeLa cancer cells, respectively. Crude aqueous extracts of P. indica root inhibited focus formation and promoted apoptosis of HeLa cells. It was found that phosphorylated-p53 and p21 were induced in GBM8401 and HeLa cells treated with crude aqueous extracts of P. indica root. Expression of phosphorylated-AKT was decreased in HeLa cells treated with crude aqueous extracts of P. indica root. Conclusion The in vitro anti-cancer effects of crude aqueous extracts of P. indica leaf and root indicate that it has sufficient potential to warrant further examination and development as a new anti-cancer

  20. Cytotoxic, antimigratory, pro-and antioxidative activities of extracts from medicinal mushrooms on colon cancer cell lines

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    Šeklić Dragana S.

    2016-01-01

    Full Text Available Methanol extracts of five commercially available mushroom species (Phellinus linteus (Berk. et Curt Teng, Cordyceps sinensis (Berk. Sacc., Lentinus edodes (Berk. Pegler, Coprinus comatus (O. F. Müll. Pers. and Ganoderma lucidum (Curtis P. Karst, traditionally used as anticancer agents, were evaluated in vitro for their total phenol and flavonoid contents, cytotoxic and antimigratory activities and antioxidant/prooxidant effects on colon cancer cell lines (HCT-116 and SW-480. Spectrophotometric methods were used for the determination of total phenol content, flavonoid concentrations and DPPH activity of the extracts. Cytotoxic activity was measured by the MTT assay. The antimigratory activity of extracts was determined using the Transwell assay and immunofluorescence staining of β-catenin. The prooxidant/antioxidant status was followed by measuring the superoxide anion radical (O2•-, nitrite and reduced glutathione (GSH concentrations. Our results show that the highest phenolic and flavonoid content was found in P. linteus, and its DPPH-scavenging capacity was significantly higher than in other samples. The P. linteus extract significantly decreased cell viability of both tested cancer cell lines. All other extracts selectively inhibited SW-480 cell viability, but did not show significant cytotoxic activity. The mushroom extracts caused changes in the prooxidant/antioxidant status of cells, inducing oxidative stress. All extracts tested on HCT-116 cells demonstrated significant antimigratory effects, which correlated with increased production of O2•- and a reduced level of β-catenin protein expression, while only P. linteus showed the same effect on SW-480 cells. The results of the present research indicate that the mushroom extracts causes oxidative stress which has a pronounced impact on the migratory status of colon cancer cell lines. [Projekat Ministarstva nauke Republike Srbije, br. III41010

  1. A Fucus vesiculosus extract inhibits estrogen receptor activation and induces cell death in female cancer cell lines.

    Science.gov (United States)

    Zhang, Jianqing; Riby, Jacques E; Conde, Lucia; Grizzle, William E; Cui, Xiangqin; Skibola, Christine F

    2016-05-28

    We previously reported the anti-estrogenic activity of the brown seaweed, Fucus vesiculosus. The present study aimed to further investigate its anti-estrogenic modes of action and to assess other potentially biologically relevant anti-tumorigenic effects in estrogen receptor (ER)-dependent and -independent female cancer cell lines. The CALUX® assay was used to determine the effect of a F. vesiculosus extract (FVE) on activation of the ER. Aromatase enzymatic activity was measured to determine the potential effect of FVE on estradiol (E2) biosynthesis. Transcriptional activity profiling of 248 genes involved in cancer, immunity, hormonal regulation, protein phosphorylation, transcription, metabolism, and cellular structure was conducted using the NanoString nCounter® analysis system in FVE-treated breast, ovarian and endometrial cancer cell lines. The effects of FVE on cell viability, morphology, membrane integrity, mitochondrial toxicity, induction of apoptotic and autophagic markers, and cell signaling were also analyzed. In co-treatments with 12.5 pM (EC50) E2, FVE (2 %) reduced ER activation by 50 %, exhibiting potent ER antagonistic effects. FVE inhibited aromatase activity in an in vitro assay (IC50 2.0 %). ER-dependent and -independent cancer cell lines showed significantly decreased viability that correlated with increasing FVE concentrations and altered morphological features suggestive of apoptosis and autophagy. Expression of genes that were significantly altered by FVE (p < 0.05) revealed predominantly apoptotic, autophagic and kinase signaling pathways. FVE also effectively inhibited the phosphorylation of Akt, resulting in reduced mTORC1 activities to stimulate autophagy in cells. Concentration-dependent cleavage of PARP and induction of caspase-3 and -7 activities were observed in MDA-MB-231 cells supporting a role for FVE in the promotion of apoptosis. Our study provides new insights into the anti-estrogenic activity of F. vesiculosus

  2. In vitro assessment of Macleaya cordata crude extract bioactivity and anticancer properties in normal and cancerous human lung cells.

    Science.gov (United States)

    Liu, Min; Lin, Yu-ling; Chen, Xuan-Ren; Liao, Chi-Cheng; Poo, Wak-Kim

    2013-09-01

    The purpose of this study is to assess the bioactivity and anticancer properties of Macleaya cordata crude extract in vitro using normal fetal lung fibroblast MRC5 and adenocarcinomic epithelial cell A549 as model systems,. Treatment of extract induced cell detachment, rounding, and irregularity in shape, in both normal and adenocarcinomic human lung cells, in accompanied of significant reduction in cell proliferation. The data indicated that necrosis appeared to be involved in compromising cell growth in both types of lung cells since membrane permeability and cell granularity were elevated. Although apoptosis was evident, the responses were differential in normal and diseased lung cells. Viability of treated MRC5 cells was reduced in a dose-dependent manner, demonstrating that the normal lung cells are sensitive to the extract. Surprisingly, A549 viability was slightly elevated in response to extract exposure at low concentration, implying that cells survived were metabolically active; the viability was reduced accordingly to treatment at higher concentrations. The present findings demonstrate that the crude extract of M. cordata contains agents affecting the functioning of normal and diseased lung cells in vitro. The observed cytotoxic effects against adenocarcinomic lung cells validate the potential of using M. cordata as herbal intervention in combined with conventional chemotherapy for lung cancer treatment. Copyright © 2012 Elsevier GmbH. All rights reserved.

  3. Ginkgo biloba exocarp extracts induces apoptosis in Lewis lung cancer cells involving MAPK signaling pathways.

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    Cao, Chenjie; Su, Ya; Han, Dongdong; Gao, Yanqi; Zhang, Menghua; Chen, Huasheng; Xu, Aihua

    2017-02-23

    A fruit of Ginkgo biloba L. is known as Ginkgo nuts. It is an edible traditional Chinese medicine, and could be used for the treatment of cancer thousands of years ago in China. The extracts prepared from the exocarp of Ginkgo biloba (Ginkgo biloba exocarp extracts, GBEE) has the effects of anti-cancer, immune promotion, anti-aging and etc. To study the effects of GBEE inducing apoptosis in Lewis lung cancer (LLC) cells and the role of Mitogen-activated protein kinase(MAPK) signaling pathways in it. The LLC solid tumor model was established in C57BL/6J mice. The tumor-bearing mice were randomly divided into 5 groups. A normal control group without tumor cells was established additionally. There were 10 mice in each group, and they were dosed 24h after inoculation. The GBEE (50, 100, 200mg/kg b.w.) groups were dosed by intragastric gavage (i.g.). The mice in positive control group were intraperitoneal (i.p.) injected with cyclophosphamide (CPA) at a dose of 20mg/kg (b.w.). The model control group and the normal control group were both given normal saline (NS) by i.g.. All the groups were dosed at a volume of 0.1mL/10g (b.w.), once a day for 18d. The day after the last administration, the transplanted tumors was stripped and weighed, and the inhibition rate was calculated. In vitro experiments, MTT method was applied to detect the effects of GBEE on LLC cells and primary cultured mouse lung cells. Annexin V-FITC/PI method was used to detect the apoptosis rate of LLC cells. Rhodamine 123 method was used to detect the Mitochondrial transmembrane potential (MTP). Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the levels of Fas mRNA. Western Blot was used to detect the expression of Bax, Bcl-2, Cyt C, cleaved Caspase-3 and MAPK proteins in the corresponding parts of LLC cells. GBEE (50-200mg/kg) inhibited the growth of LLC transplanted tumors with a dose-effect relationship. GBEE (5-160µg/mL) inhibited the proliferation of LLC

  4. Analysis of the Interactions of Botanical Extract Combinations Against the Viability of Prostate Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Lynn S. Adams

    2006-01-01

    Full Text Available Herbal medicines are often combinations of botanical extracts that are assumed to have additive or synergistic effects. The purpose of this investigation was to compare the effect of individual botanical extracts with combinations of extracts on prostate cell viability. We then modeled the interactions between botanical extracts in combination isobolographically. Scutellaria baicalensis, Rabdosia rubescens, Panax-pseudo ginseng, Dendranthema morifolium, Glycyrrhiza uralensis and Serenoa repens were collected, taxonomically identified and extracts prepared. Effects of the extracts on cell viability were quantitated in prostate cell lines using a luminescent ATP cell viability assay. Combinations of two botanical extracts of the four most active extracts were tested in the 22Rv1 cell line and their interactions assessed using isobolographic analysis. Each extract significantly inhibited the proliferation of prostate cell lines in a time- and dose-dependent manner except repens. The most active extracts, baicalensis, D. morifolium, G. uralensis and R. rubescens were tested as two-extract combinations. baicalensis and D. morifolium when combined were additive with a trend toward synergy, whereas D. morifolium and R. rubescens together were additive. The remaining two-extract combinations showed antagonism. The four extracts together were significantly more effective than the two-by-two combinations and the individual extracts alone. Combining the four herbal extracts significantly enhanced their activity in the cell lines tested compared with extracts alone. The less predictable nature of the two-way combinations suggests a need for careful characterization of the effects of each individual herb based on their intended use.

  5. Analysis of the Interactions of Botanical Extract Combinations Against the Viability of Prostate Cancer Cell Lines

    Science.gov (United States)

    Adams, Lynn S.; Seeram, Navindra P.; Hardy, Mary L.; Carpenter, Catherine; Heber, David

    2006-01-01

    Herbal medicines are often combinations of botanical extracts that are assumed to have additive or synergistic effects. The purpose of this investigation was to compare the effect of individual botanical extracts with combinations of extracts on prostate cell viability. We then modeled the interactions between botanical extracts in combination isobolographically. Scutellaria baicalensis, Rabdosia rubescens, Panax-pseudo ginseng, Dendranthema morifolium, Glycyrrhiza uralensis and Serenoa repens were collected, taxonomically identified and extracts prepared. Effects of the extracts on cell viability were quantitated in prostate cell lines using a luminescent ATP cell viability assay. Combinations of two botanical extracts of the four most active extracts were tested in the 22Rv1 cell line and their interactions assessed using isobolographic analysis. Each extract significantly inhibited the proliferation of prostate cell lines in a time- and dose-dependent manner except S. repens. The most active extracts, S. baicalensis, D. morifolium, G. uralensis and R. rubescens were tested as two-extract combinations. S. baicalensis and D. morifolium when combined were additive with a trend toward synergy, whereas D. morifolium and R. rubescens together were additive. The remaining two-extract combinations showed antagonism. The four extracts together were significantly more effective than the two-by-two combinations and the individual extracts alone. Combining the four herbal extracts significantly enhanced their activity in the cell lines tested compared with extracts alone. The less predictable nature of the two-way combinations suggests a need for careful characterization of the effects of each individual herb based on their intended use. PMID:16550232

  6. Elaeagnus angustifolia Plant Extract Inhibits Angiogenesis and Downgrades Cell Invasion of Human Oral Cancer Cells via Erk1/Erk2 Inactivation.

    Science.gov (United States)

    Saleh, Alaaeldin I; Mohamed, Islam; Mohamed, Ahmed A; Abdelkader, Mennatallah; Yalcin, Huseyin C; Aboulkassim, Tahar; Batist, Gerald; Yasmeen, Amber; Moustafa, Ala-Eddin Al

    2018-01-01

    Oral cancer is a common malignancy in both men and women worldwide; this cancer is characterized by a marked propensity for invasion and spreading to local lymph nodes. On the other hand, Elaeagnus angustifolia (EA) is a medicinal plant that has been used for centuries for treating many human diseases in the Middle East. However, the effect of EA plant extract on human cancers especially oral has not been investigated yet. Thus, first we examined the outcome of EA flower extract on angiogenesis, using the chorioallantoic membrane (CAM) of the chicken embryo; we found that EA extract reduces blood vessel development of the CAM. Then, we investigated the effect of EA flower extract on selected parameters in FaDu and SCC25 oral cancer cell lines. Our results show that EA extract inhibits cell proliferation and colony formation, in addition to the initiation of S cell cycle arrest and reduction of G1/G2 phase. In parallel, EA extract provokes differentiation to an epithelial phenotype "mesenchymal-to-epithelial transition: MET" which is the opposite of "epithelial-to-mesenchymal transition, EMT": an important event in cell invasion and metastasis. Thus, EA plant extract causes a dramatic decrease in cell invasion and motility abilities of FaDu and SCC25 cancer cells in comparison with their controls. These changes are accompanied by an upregulation of E-cadherin expression. The molecular pathway analysis of the EA flower extract reveals that it can inhibit the phosphorylation of Erk1/Erk2, which could be behind the inhibition of angiogenesis, the initiation of MET event, and the overexpression of E-cadherin. Our findings indicate that EA plant extract can reduce human oral cancer progression by the inhibition of angiogenesis and cell invasion via Erk1/Erk2 signaling pathways.

  7. Characterizing components of the Saw Palmetto Berry Extract (SPBE) on prostate cancer cell growth and traction.

    Science.gov (United States)

    Scholtysek, Carina; Krukiewicz, Aleksandra A; Alonso, José-Luis; Sharma, Karan P; Sharma, Pal C; Goldmann, Wolfgang H

    2009-02-13

    Saw Palmetto Berry Extract (SPBE) is applied for prostate health and treatment of urinary tract infections, nonbacterial prostitis and Benign Prostatic Hyperplasia (BPH) in man. An assumption is that SPBE affects tumor cell progression and migration in breast and prostate tissue. In this work, DU-145 cells were used to demonstrate that SPBE and its sterol components, beta-sitosterol and stigmasterol, inhibit prostate cancer growth by increasing p53 protein expression and also inhibit carcinoma development by decreasing p21 and p27 protein expression. In the presence of cholesterol, these features are not only reversed but increased significantly. The results show for the first time the potential of SPBE, beta-sitosterol and stigmasterol as potential anti-tumor agents. Since the protein p53 is also regarded as nuclear matrix protein facilitating actin cytoskeletal binding, 2D tractions were measured. The cell adhesion strength in the presence of SPBE, beta-sitosterol and cholesterol and the observation was that the increase in p53 expression triggered an increase in the intracellular force generation. The results suggest a dual function of p53 in cells.

  8. Evaluation of apoptotic activity of Withania coagulans methanolic extract against human breast cancer and Vero cell lines.

    Science.gov (United States)

    Ahmad, Rumana; Fatima, Afreen; Srivastava, A N; Khan, Mohsin Ali

    The genus Withania (Family: Solanaceae) holds an important position in Ayurveda, the Indian traditional system of medicine. Withania somnifera Dunal and Withania coagulans Dunal have been documented in folklore as panaceas for various ailments since time immemorial. W. coagulans (WC), commonly called as Indian cheese maker is used for fermenting milk for cheese production in various parts of India. In the study, in vitro cytotoxicity of methanolic extract of dried fruits (berries) of WC was evaluated in a dose dependent manner using trypan blue dye exclusion method against human breast cancer cell line MDA-MB-231 and normal kidney epithelial cell line Vero in the range 20-200 μg/ml. The percentage viability of the cell lines was determined by using MTT assay and cytometry. Methanolic extract of WC showed significant anticancer activity against MDA-MB-231 cell line. Cell viability was reduced to about 50% at 40 μg/ml of methanolic extract in 50% DMSO. Cytotoxicity of the extract was lower in 10% and 1% DMSO. On the other hand, methanolic extract of WC did not exhibit any significant in vitro activity against Vero cells at 170 and 200 μg/ml. AGE of isolated DNA from treated cancer cells revealed characteristic ladder like fragmentation, a hallmark of apoptosis. HPLC profiling was carried out for identification of the active components, which demonstrated the presence of Withaferin A in the methanolic extract. Methanolic extract of WC possesses apoptotic activity against human breast cancer cells in vitro albeit lower in comparison to W. somnifera and warrants further investigation. Copyright © 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

  9. Chemical composition of Solanum nigrum linn extract and induction of autophagy by leaf water extract and its major flavonoids in AU565 breast cancer cells.

    Science.gov (United States)

    Huang, Hsiu-Chen; Syu, Kai-Yang; Lin, Jen-Kun

    2010-08-11

    Solanum nigrum Linn (SN) belongs to the Solanaceae family, is a plant growing widely in south Asia, and has been used in traditional folk medicine. It is believed to have antipyretic, diuretic, anticancer, and hepatoprotective effects. During the summertime, this plant has been heavily used to supplement beverages to quench thirst on hot days in Taiwan and several southern Asian countries. In this study, the polyphenols and anthocyanidin in various parts of the SN plant were analyzed by HPLC. The leaves were found to be richer in polyphenols than stem and fruit. SN leaves contained the highest concentration of gentisic acid, luteolin, apigenin, kaempferol, and m-coumaric acid. However, the anthocyanidin existed only in the purple fruits. Additionally, the cytotoxicity of the leaf, stem, or fruit extract was evaluated against cancer cell lines and normal cells. The results showed that AU565 breast cancer cells were more sensitive to the extract. Furthermore, the results demonstrated a significant cytotoxic effect of SN leaf extract on AU565 cells that was mediated via two different mechanisms depending on the exposure concentrations. A low dose of SN leaf extract induced autophagy but not apoptosis. Higher doses (>100 microg/mL) of SN leaf extract could inhibit the level of p-Akt and cause cell death due to the induction of autophagy and apoptosis. However, these findings indicate that SN leaf extract induced cell death in breast cells via two distinct antineoplastic activities, the abilities to induce apoptosis and autophagy, therefore suggesting that it may provide a useful remedy to treat breast cancer.

  10. Polyphenolic Profile and Targeted Bioactivity of Methanolic Extracts from Mediterranean Ethnomedicinal Plants on Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Antonino Pollio

    2016-03-01

    Full Text Available The methanol extracts of the aerial part of four ethnomedicinal plants of Mediterranean region, two non-seed vascular plants, Equisetum hyemale L. and Phyllitis scolopendrium (L. Newman, and two Spermatophyta, Juniperus communis L. (J. communis and Cotinus coggygria Scop. (C. coggygria, were screened against four human cells lines (A549, MCF7, TK6 and U937. Only the extracts of J. communis and C. coggygria showed marked cytotoxic effects, affecting both cell morphology and growth. A dose-dependent effect of these two extracts was also observed on the cell cycle distribution. Incubation of all the cell lines in a medium containing J. communis extract determined a remarkable accumulation of cells in the G2/M phase, whereas the C. coggygria extract induced a significant increase in the percentage of G1 cells. The novelty of our findings stands on the observation that the two extracts, consistently, elicited coherent effects on the cell cycle in four cell lines, independently from their phenotype, as two of them have epithelial origin and grow adherent and two are lymphoblastoid and grow in suspension. Even the expression profiles of several proteins regulating cell cycle progression and cell death were affected by both extracts. LC-MS investigation of methanol extract of C. coggygria led to the identification of twelve flavonoids (compounds 1–11, 19 and eight polyphenols derivatives (12–18, 20, while in J. communis extract, eight flavonoids (21–28, a α-ionone glycoside (29 and a lignin (30 were found. Although many of these compounds have interesting individual biological activities, their natural blends seem to exert specific effects on the proliferation of cell lines either growing adherent or in suspension, suggesting potential use in fighting cancer.

  11. Methanolic extract of adlay seed suppresses COX-2 expression of human lung cancer cells via inhibition of gene transcription.

    Science.gov (United States)

    Hung, Wen-Chun; Chang, Hui-Chiu

    2003-12-03

    Previous results demonstrated that the methanolic extract of adlay seed exerted an antiproliferative effect on human lung cancer cells in vitro and in vivo and might prevent tobacco carcinogen-induced lung tumorigenesis. In this study, the methanolic extract of adlay seed was tested for its regulation of COX-2 expression of human lung cancer cells. Western blot analysis showed that the methanolic extract of adlay seed inhibited basal and TPA-induced COX-2 expression in a dose-dependent fashion, whereas COX-1 expression was not affected. By using a promoter activity assay, it was found that the methanolic extract inhibited basal and TPA-stimulated COX-2 expression at the transcription level. The effect of the methanolic extract on COX-2 expression in vivo was then investigated. The data demonstrated that treatment of the methanolic extract reduced the PGE(2) level in serum and inhibited COX-2 expression of tumor tissues in nude mice. Taken together, these results suggest that inhibition of COX-2 is one of the mechanisms by which the methanolic extract of adlay seed inhibits cancer growth and prevents lung tumorigenesis.

  12. Identification of bioactive constituents of Ziziphus jujube fruit extracts exerting antiproliferative and apoptotic effects in human breast cancer cells.

    Science.gov (United States)

    Plastina, Pierluigi; Bonofiglio, Daniela; Vizza, Donatella; Fazio, Alessia; Rovito, Daniela; Giordano, Cinzia; Barone, Ines; Catalano, Stefania; Gabriele, Bartolo

    2012-03-27

    Ziziphus extracts have been used in Traditional Chinese Medicine for the treatment of cancer. In the present study we have investigated the effects of Ziziphus jujube extracts (ZEs) on breast cancer. We evaluated the effects of increasing concentrations of ZEs on ERα positive MCF-7 and ERα negative SKBR3 breast cancer cell proliferation using MTT assays. Apoptosis was analyzed by evaluating the involvement of some pro-apoptotic proteins, including Bax, Bad, Bid and PARP cleavage by immunoblotting analysis. Moreover, the effects of ZEs treatment on apoptosis were tested by both DNA fragmentation and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) staining. By using chromatographic techniques, we identified the constituents of the effective extracts. ZE1, ZE2, and ZE4 exerted significant antiproliferative effects on estrogen receptor alpha (ERα) positive MCF-7 (IC(50) values of 14.42, 7.64, 1.69μg/mL) and ERα negative SKBR3 (IC(50) values of 14.06, 6.21, 3.70μg/mL) human breast cancer cells. Remarkably, ZEs did not affect cell viability of both normal human fibroblasts BJ1-hTERT and nonmalignant breast epithelial MCF-10A cells. Treatment with ZEs induced cell death by apoptosis in both malignant breast cells. We found that the most effective extracts ZE2 and ZE4 shared a number of triterpenic acids, already known for their anticancer activities. Our data provide a rational base for the use of Ziziphus extracts in the treatment of breast cancer in Traditional Chinese Medicine. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  13. Portulaca oleracea extract can inhibit nodule formation of colon cancer stem cells by regulating gene expression of the Notch signal transduction pathway.

    Science.gov (United States)

    Jin, Heiying; Chen, Li; Wang, Shuiming; Chao, Deng

    2017-07-01

    To investigate whether Portulaca oleracea extract affects tumor formation in colon cancer stem cells and its chemotherapy sensitivity. In addition, to analyze associated genetic changes within the Notch signal transduction pathway. Serum-free cultures of colon cancer cells (HT-29) and HT-29 cancer stem cells were treated with the chemotherapeutic drug 5-fluorouracil to assess sensitivity. Injections of the stem cells were also given to BALB/c mice to confirm tumor growth and note its characteristics. In addition, the effect of different concentrations of P. oleracea extract was tested on the growth of HT-29 colon cancer cells and HT-29 cancer stem cells, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The effects of P. oleracea extract on the expression of β-catenin, Notch1, and Notch2 in the HT-29 cells were studied using reverse transcription polymerase chain reaction and Western blotting. The tumor volume of the HT29 cells was two times larger than that of HT29 cancer stem cells. Treatment with P. oleracea extract inhibited the proliferation of both HT-29 cancer cells and HT-29 cancer stem cells at doses from 0.07 to 2.25 µg/mL. Apoptosis of HT-29 cancer cells and HT-29 cancer stem cells was assessed by flow cytometry; it was enhanced by the addition of P. oleracea extract. Finally, treatment with P. oleracea extract significantly downregulated the expression of the Notch1 and β-catenin genes in both cell types. The results of this study show that P. oleracea extract inhibits the growth of colon cancer stem cells in a dose-dependent manner. Furthermore, it inhibits the expression of the Notch1 and β-catenin genes. Taken together, this suggests that it may elicit its effects through regulatory and target genes that mediate the Notch signal transduction pathway.

  14. Proliferative effects of five traditional Nigerian medicinal plant extracts on human breast and bone cancer cell lines.

    Science.gov (United States)

    Engel, N; Oppermann, C; Falodun, A; Kragl, U

    2011-09-02

    The medicinal plants Hunteria umbellata (HUL), Cola lepidota (CCL), Persea americana leaf (PAL), Root bark of Persea americana (RPA) and Plukenetia conophora (PCL) are used in Nigerian traditional medicine for the treatment of cancer and cancer related diseases. To scientifically evaluate the cell proliferative and apoptotic effects of the plants extracts using breast and osteocarcinoma cell lines, and also to identify the possible components via LC-MS to have a kind of chemical fingerprint. The antiproliferative and apoptotic effects of methanolic extracts (10 μg/ml) of the five medicinal plants were subjected to in vitro evaluation using four cancer cell lines (breast-MCF-7 and BT-20; Osteocarcinoma-MG-63 and Saos-2) measured by flow cytometry. Non-tumorigenic controls MCF-12A and primary isolated osteoblasts (POB) were chosen to eliminate negative influence on healthy tissue. Of the five extracts RPA demonstrated a significant (P<0.05) anti-proliferative activity against estrogen receptor positive breast cancer cell lines (MCF-7). The proliferative phase was decreased by 18%, whereas, a significant increase in cell proliferation (about 27%) was observed for RPA at a concentration of 10 μg/ml. PCL, CCL, HUL and PAL did not show marked inhibition of the proliferation of cell line MCF-7. These results give suggestive evidence that the plant extracts exhibit some correlation between the claimed ethnomedicinal uses and the cell proliferative activity. RPA extract includes chemical compounds with estrogen-like activity and validates its potential use as anticancer agent, particularly against breast carcinoma; provided important information potentially helpful in drug designing and discovery. Further studies will involve the isolation of anti tumour compounds in RPA by LC-MS and detailed mechanism of anticancer activities. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. Ethanol extract of Brazilian red propolis induces apoptosis in human breast cancer MCF-7 cells through endoplasmic reticulum stress.

    Science.gov (United States)

    Kamiya, Tetsuro; Nishihara, Hiroko; Hara, Hirokazu; Adachi, Tetsuo

    2012-11-07

    Propolis, a natural product collected from plants by honey bees, is commonly used in folk medicines. Endoplasmic reticulum (ER) stress is known to induce apoptosis through the induction of CCAAT/enhancer-binding protein homologous protein (CHOP). Here, we investigated whether ethanol extracts of propolis and caffeic acid phenethyl ester (CAPE) induce apoptosis, mitochondrial dysfunction, and ER stress in human breast cancer MCF-7 cells and human fibroblasts. Among several ethanol extracts of propolis and CAPE, Brazilian red propolis (BRP) significantly reduced MCF-7 cell viability through the induction of mitochondrial dysfunction, caspase-3 activity, and DNA fragmentation but did not affect those of fibroblasts. Moreover, treatment with BRP significantly induced CHOP expression in MCF-7 cells compared to fibroblasts. Further, pretreatment with a chemical chaperone, 4-phenylbutyric acid, suppressed BRP-triggered MCF-7 cell death. Overall, we revealed that an ethanol extract of BRP induces MCF-7 cell apoptosis through, at least in part, ER stress-related signaling.

  16. Autophagy Inhibition Enhances the Mitochondrial-Mediated Apoptosis Induced by Mangrove (Avicennia marina) Extract in Human Breast Cancer Cells

    KAUST Repository

    Esau, Luke

    2015-01-10

    Aims: Avicennia marina (AM) is a widely distributed mangrove plant that has been used in traditional medicine for centuries for the treatment of a number of diseases. The objective of the present study was to evaluate the leaf ethyl acetate extract of AM for its cytotoxic and apoptotic potential along with in-depth investigations of its mechanism of action in breast cancer MCF-7 cells. Study Design: The ethyl acetate extract of leaves and stems of AM was tested against estrogen positive breast cancer cell line MCF-7 using various assays. Place and Duration of Study: The study was carried out at King Abdullah University of Science and Technology, Thuwal, Saudi Arabia, from July 2013-June 2014. Methodology: Dose- and time-dependent growth inhibition of cancer cells was measured using MTT assay. The mechanisms of apoptosis induction were determined using various assays: phosphatidylserine exposure, caspase-3/7 activation, mitochondrial membrane potential disruption, reactive oxygen species (ROS) production, cell cycle analysis, autophagy, and protein expression using western blotting. The modulation of apoptotic genes (p53, Mdm2, NF-kB, Bad, Bax, Bcl-2 and Casp7) was also determined using real time PCR. Results: The AM extract inhibited breast cancer cell growth and induced apoptosis in a concentration dependent manner. We demonstrated a non-classical mode of apoptosis induction in MCF-7 cells by AM extract, where ROS production altered the mitochondrial membrane potential to induce apoptosis. Breast cancer cells treated with 200 µg/ml concentration of AM extract showed increased ROS production and disrupted MMP but no PARP-1 cleavage and a marked decrease in Caspase-7 protein levels (24 and 48 h) were detected. A significant amount of autophagy was also observed at the same concentration. However, treatment of MCF-7 cells with 200 µg/ml of AM extract along with the inhibition of autophagy by chloroquine, significantly increased the apoptosis from 20% to 45

  17. Determination of glucose in human stomach cancer cell extracts and single cells by capillary electrophoresis with a micro-biosensor.

    Science.gov (United States)

    Wang, Xiaolei; Ma, Yanfang; Zhao, Man; Zhou, Minfeng; Xiao, Yan; Sun, Zifei; Tong, Lili

    2016-10-21

    Bioactive species in cells can provide information about signal transduction, cell function, and the effects of disease treatment. In this article, a novel micro-biosensor was fabricated to detect glucose in individual human stomach cancer cells (MGC80-3 cells) with capillary electrophoresis (CE). We fabricated the micro-biosensors by immobilizing a single-walled carbon nanotube-glucose oxidase (GOx)-glutaraldehyde (GA) bio-composite at the palladium nanoparticle (PdNPs) modified Pt electrode. The linear concentration of glucose ranged from 2.0μM to 1.0mM, with a detection limit of 0.5μM. Using this method, the mean amount of glucose in MGC80-3 cell extracts and in single cells was 20.0 fmol and 20±6 fmol (n=10), respectively. The micro-biosensor exhibited high sensitivity, stability, and a long operating life, which are likely due to the biocompatible environment provided by BSA and GA, and the adsorption and faster electron transfer of SWNTs and PdNPs to GOx. Copyright © 2016. Published by Elsevier B.V.

  18. pH-dependent cytotoxic effects of extracts of the marine sponge Polymastia janeirensis on cancer cell lines.

    Science.gov (United States)

    Biegelmeyer, Renata; Schröder, Rafael; Rambo, Douglas F; Dresch, Roger R; Carraro, João L F; Mothes B, Beatriz; Moreira, José Cláudio F; da Frota Junior, Mario L C; Henriques, Amélia T

    2016-02-09

    The purpose of this work was to study the cytotoxic effects of marine sponge Polymastia janeirensis, which has been observed in the field to release an orange substance that is toxic to fish. The result showed that aqueous extract (pH 7.0) was highly cytotoxic to glioma (U87) and neuroblastoma (SHSY5Y) cancer cell lines (IC 50  antioxidant and procoagulant (decreased the clotting time by 1.7-fold) activities. Interestingly, the cytotoxic effects were pH-dependent since the viability of the cancer cells was not affected with the extract (pH 5.5). The close similarity between the aqueous extract (pH 7.0) and the orange liquid that is released by the sponge indicates that this potential chemical defence of P. janeirensis deserves further investigation.

  19. The Cytotoxic Effect of Small and Large Molecules of PMF Fraction Extracted from Camel Urine on Cancer Cells

    KAUST Repository

    Khorshid, Faten

    2015-01-10

    Aim of the work: Animal urine, including that of camels, has long been used for the therapeutic management of human ailments. In this study, we sought to characterize the cytotoxic properties of newly derived purified fractions from previously described camel urine extract (PMF) on various cancer cell lines. Methodology: Two new size dissimilar fractions of PMF (large and small) were obtained by fractionalizing PMF using 3kD and 50kD membrane filters. A SRB cytotoxicity assay of the PMF fractions was performed on cancer cell lines (A549, HCT116, HepG2, MCF-7, U251 and Hela) as well as normal cell lines (human fibroblast cell line and Vero). Results: This study showed that the newly derived and more purified fraction of PMF (new PMF) possesses effective and selective anti-cancer properties against several types of cancer cell lines. Conclusion: This study, as well as previous ones, suggests that camel urine extracts (old and new PMF) may provide newer therapeutic alternatives to clinically manage cancer patients. However, further studies are needed to verify these positive preliminary results.

  20. Anticancer Activity and Molecular Mechanism of Polyphenol Rich Calophyllum inophyllum Fruit Extract in MCF-7 Breast Cancer Cells.

    Science.gov (United States)

    Shanmugapriya; Chen, Yeng; Kanwar, Jagat R; Sasidharan, Sreenivasan

    2017-10-25

    This study was conducted to investigate the anticancer effects and mechanism of Calophyllum inophyllum fruit extract against MCF-7 cells. C. inophyllum fruit extract was found to have markedly cytotoxic effect against MCF-7 cells in a dose-dependent manner with the IC50 for 24 h of 23.59 µg/mL. Flow cytometry analysis revealed that C. inophyllum fruit extract mediated cell cycle at G0/G1 and G2/M phases, and MCF-7 cells entered the early phase of apoptosis. The expression of anti-apoptotic proteins Bcl-2 was decreased whereas the expression of the pro-apoptotic protein Bax, cytochrome C and p53 were increased after treatment. C. inophyllum fruit extract led to apoptosis in MCF-7 cells via the mitochondrial pathway in a dose dependent manner. This is evidenced by the elevation of intracellular ROS, the loss of mitochondria membrane potential (Δψm), and activation of caspase-3. Meanwhile, dose-dependent genomic DNA fragmentation was observed after C. inophyllum fruits extract treatment by comet assay. This study shows that C. inophyllum fruits extract-induced apoptosis is primarily p53 dependent and mediated through the activation of caspase-3. C. inophyllum fruit extract could be an excellent source of chemopreventive agent in the treatment of breast cancer and has potential to be explored as green anticancer agent.

  1. The influence of Osmunda regalis root extract on head and neck cancer cell proliferation, invasion and gene expression.

    Science.gov (United States)

    Schmidt, Marianne; Skaf, Josef; Gavril, Georgiana; Polednik, Christine; Roller, Jeanette; Kessler, Michael; Holzgrabe, Ulrike

    2017-12-04

    According to only a handful of historical sources, Osmunda regalis, the royal fern, has been used already in the middle age as an anti-cancer remedy. To examine this ancient cancer cure, an ethanolic extract of the roots was prepared and analysed in vitro on its effectiveness against head and neck cancer cell lines. Proliferation inhibition was measured with the MTT assay. Invasion inhibition was tested in a spheroid-based 3-D migration assay on different extracellular matrix surfaces. Corresponding changes in gene expression were analysed by qRT-PCR array. Induction of apoptosis was measured by fluorescence activated cell sorting (FACS) with the Annexin V binding method. The plant extract was analysed by preliminary phytochemical tests, liquid chromatography/mass spectroscopy (LC-MS) and thin layer chromatography (TLC). Anti-angiogenetic activity was determined by the tube formation assay. O. regalis extract revealed a growth inhibiting effect on the head and neck carcinoma cell lines HLaC78 and FaDu. The toxic effect seems to be partially modulated by p-glycoprotein, as the MDR-1 expressing HLaC79-Tax cells were less sensitive. O. regalis extract inhibited the invasion of cell lines on diverse extracellular matrix substrates significantly. Especially the dispersion of the highly motile cell line HlaC78 on laminin was almost completely abrogated. Motility inhibition on laminin was accompanied by differential gene regulation of a variety of genes involved in cell adhesion and metastasis. Furthermore, O. regalis extract triggered apoptosis in HNSCC cell lines and inhibited tube formation of endothelial cells. Preliminary phytochemical analysis proved the presence of tannins, glycosides, steroids and saponins. Liquid chromatography/mass spectroscopy (LC-MS) revealed a major peak of an unknown substance with a molecular mass of 864.15 Da, comprising about 50% of the total extract. Thin layer chromatography identified ferulic acid to be present in the extract. The

  2. Taraxacum mongolicum extract induced endoplasmic reticulum stress associated-apoptosis in triple-negative breast cancer cells.

    Science.gov (United States)

    Li, Xiao-Hong; He, Xi-Ran; Zhou, Yan-Yan; Zhao, Hai-Yu; Zheng, Wen-Xian; Jiang, Shan-Tong; Zhou, Qun; Li, Ping-Ping; Han, Shu-Yan

    2017-07-12

    Triple-negative breast cancer (TNBC) is an aggressive and deadly breast cancer subtype with limited treatment options. It is necessary to seek complementary strategies for TNBC management. Taraxacum mongolicum, commonly named as dandelion, is a herb medicine with anti-cancer activity and has been utilized to treat mammary abscess, hyperplasia of mammary glands from ancient time in China, but the scientific evidence and action mechanisms still need to be studied. This study was intended to investigate the therapeutic effect and molecular mechanisms of dandelion extract in TNBC cell line. Dandelion extract was prepared and purified, and then its chemical composition was determined. Cell viability was evaluated by MTT assay. Analysis of cell apoptosis and cell cycle was assessed by flow cytometry. The expression levels of mRNA and proteins were determined by real-time PCR and Western blotting, respectively. Caspase inhibitor Z-VAD-FMK and CHOP siRNA were used to confirm the cell apoptosis induced by dandelion extract. Dandelion extract significantly decreased MDA-MB-231cell viability, triggered G2/M phase arrest and cell apoptosis. Concurrently, it caused a markedly increase of cleaved caspase-3 and PARP proteins. Caspase inhibitor Z-VAD-FMK abolished the apoptosis triggered by dandelion extract. The three ER stress-related signals were strongly induced after dandelion treatment, including increased mRNA expressions of ATF4, ATF6, XBP1s, GRP78 and CHOP genes, elevated protein levels of phosphorylated PERK, eIF-2α, IRE1, as well as the downstream molecules of CHOP and GRP78. MDA-MB-231 cells transfected with CHOP siRNA significantly reduced apoptosis induced by dandelion extract. The underlying mechanisms at least partially ascribe to the strong activation of PERK/p-eIF2α/ATF4/CHOP axis. ER stress related cell apoptosis accounted for the anti-cancer effect of dandelion extract, and these findings support dandelion extract might be a potential therapeutic approach to

  3. Evaluations of thyme extract effects in human normal bronchial and tracheal epithelial cell lines and in human lung cancer cell line.

    Science.gov (United States)

    Oliviero, Marinelli; Romilde, Iannarelli; Beatrice, Morelli Maria; Matteo, Valisi; Giovanna, Nicotra; Consuelo, Amantini; Claudio, Cardinali; Giorgio, Santoni; Filippo, Maggi; Massimo, Nabissi

    2016-08-25

    Thyme (Thymus vulgaris) is used traditionally to prepare herbal remedies possessing expectorant, mucolytic, antitussive and antispasmodic properties. The aim of the present study was to investigate the effects of a standardized hydroalcoholic extract of thyme on primary human airway (bronchial/tracheal) epithelial cell lines in a model of lung inflammation induced by LPS. In addition, the effects of thyme extract on human lung cancer cell line (H460) were analysed. Thyme extract showed significant anti-inflammatory properties by reducing the NF-κB p65 and NF-κB p52 transcription factors protein levels followed by the decrease of pro-inflammatory cytokines (IL-1 beta and IL-8), and Muc5ac secretion in human normal bronchial and tracheal epithelial cells. Moreover, the extract showed cytotoxic effects on H460 cancer cells, modulated the release of IL-1 beta, IL-8 and down-regulated NF-κB p65 and NF-κB p52 proteins. Taken together, these results substantiated the traditional uses of thyme in the treatment of respiratory diseases. Thyme extract might be an effective treatment of chronic diseases based on inflammatory processes when hypersecretion of mucus overwhelms the ciliary clearance and obstructs airways, causing morbidity and mortality. Moreover thyme extract, evaluated in H460 lung cancer cell line, demonstrated to induce cell cytotoxicity in addition to reduce inflammatory cell signals. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Evaluation of the Anti-proliferative Effects of Ophiocoma erinaceus Methanol Extract Against Human Cervical Cancer Cells.

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    Baharara, Javad; Amini, Elaheh; Namvar, Farideh

    2016-01-01

    Marine organisms provide appreciable source of novel bioactive compounds with pharmacological potential. There is little information in correlation with anti-cancer activities of brittle star. In the present study, anti-neoplastic efficacy of Ophiocoma erinaceus methanol extract against human cervical cancer cells was investigated. The HeLa cells were cultured and exposed to brittle star methanol extract for 24 and 48 hr. The anti-proliferative properties were examined by MTT assay and the type of cell death induced was evaluated through morphological changes, flow cytometry, Annexin kit and caspase assay. To assess the anti-metastatic activity, wound healing assay was conducted and photographs were taken from the scratched areas. Further, to understand molecular mechanism of cell apoptosis, the expression of Bax was evaluated. The morphological analysis and MTT assay exhibited that the brittle star methanol extract can exert dose dependent inhibitory effect on cells viability (IC50, 50 μg/ml). Flow cytometry and fluorescence microscopy demonstrated increment of sub-G1 peak, early and late apoptosis in HeLa treated cells. Wound healing migration assay showed that brittle star extract has anti-neoplastic efficacy by inhibiting cell migration. Caspase assay and RT-PCR analysis revealed that brittle star methanol extract induced caspase dependent apoptosis in HeLa cells through up-regulation of caspase-3 followed by up-regulation of Bax gene which is a hallmark of intrinsic pathway recruitment. These results represented further insights into the chemopreventive potential of brittle star as a valuable source of unknown therapeutic agents against human cervical cancer.

  5. Crude ethyl acetate extract of marine microalga, Chaetoceros calcitrans, induces Apoptosis in MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Goh, Su Hua; Alitheen, Noorjahan Banu Mohamed; Yusoff, Fatimah Md; Yap, Swee Keong; Loh, Su Peng

    2014-01-01

    Marine brown diatom Chaetoceros calcitrans and green microalga Nannochloropsis oculata are beneficial materials for various applications in the food, nutraceutical, pharmaceutical and cosmeceutical industries. This study investigated cytotoxicity of different crude solvent extracts from C. calcitrans and N. oculata against various cancer cell lines. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was carried out to screen the cytotoxic effects of hexane (Hex), dichloromethane (DCM), ethyl acetate, and methanol extract from C. calcitrans and N. oculata toward various cancer cell lines. Flow cytometry cell cycle was used to determine the cell cycle arrest while the mode of cell death was investigated through acridine orange/propidium iodide (AOPI) staining, Annexin V-Fluorescein Isothiocyanate (FITC) and Terminal deoxynucleotidyl transferase-mediated d-UTP Nick End Labeling (TUNEL) assays. Expression profile of apoptotic and proliferative-related genes was then determined using the multiplex gene expression profiler (GeXP). Crude ethyl acetate (CEA) extract of C. calcitrans inhibited growth of MDA-MB-231 cells, with IC50 of 60 μg/mL after 72 h of treatment. Further studies were conducted to determine the mode of cell death at various concentrations of this extract: 30, 60 and 120 μg/mL. The mode of cell death was mainly apoptosis as shown through apoptosis determination test. The expression data from GeXP showed that caspase-4 was upregulated while B-cell leukemia/lymphoma 2(Bcl-2) was down regulated. Thus, caspase-4 induction endoplasmic reticulum death pathway is believed to be one of the mechanisms underlying the induction of apoptosis while Bcl-2 induced S and G2/M cell cycle phase arrest in MDA-MB-231 cells. CEA extract of C. calcitrans showed the highest cytotoxicity on MDA-MB-231 via apoptosis.

  6. Dichloromethane-methanol extract from Borassus aethiopumn mart. (Arecaceae) induces apoptosis of human colon cancer HT-29 cells.

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    Sakandé, J; Rouet-benzineb, P; Devaud, H; Nikiema, J B; Lompo, M; Nacoulma, O G; Guissou, I P; Bado, A

    2011-05-15

    Borassus aetihiopum MART (Arecaceae) is a plant used in traditional herbal medicine for the treatment of various diseases (bronchitis, laryngitis, antiseptic). In particular, their male inflorcscences were reported to exhibit cicatrizing, antiseptic and fungicidal properties. In the present study, the biological activity of E2F2, an apolar extract from Borassus aethiopum male inflorescence was investigated on colon cancer HT29 cells. Phytochemical screening was carried according to methodology for chemical analysis for vegetable drugs. Cells proliferation was determined by the MTT assay and cells cycle distribution was analysed by using laser flow cytometer (Beckman coulter). The cytoskeleton organisation was examined under a laser scanning confocal microscope (Zess). Preliminary phytochemical analysis of E2F2 extract revealed the presence of sterols, triterpenes and saponosids. E2F2 extract (1 microg and 100 microg mL(-1)) significantly inhibited cell proliferation by blocking cell population in G0/G1 phase. Flow Cytometric analysis of E2F2-treated HT29 cells showed that hypoploïd cell population (sub G1 phase) increased with processing time exposures. Immunofluorescence confocal analysis revealed a disrupt actin microfilaments network in E2F2 treated-cells with a significant reduction in actin stress fibres and appearance of a random, non-oriented distribution of focal adhesion sites. These data indicate that E2F2 extract has anti-proliferative and pro-apoptotic activities. Further studies are required to unravel the mechanisms of action of E2F2 extract.

  7. Acetonitrile extract of Salvia miltiorrhiza Radix exhibits growth-inhibitory effects on prostate cancer cells through the induction of cell cycle arrest and apoptosis.

    Science.gov (United States)

    Lee, June; Choi, Bu Young; Keum, Young-Sam

    2017-05-01

    In the present study, the effects of the acetonitrile or water extracts from 400 selected traditional medicinal plants on the growth of PC-3 cells were investigated, and it was demonstrated that an acetonitrile extract of Salvia miltiorrhiza Radix exhibited the most marked cytotoxic effects on PC-3 cells. It was observed that the acetonitrile extract of S. miltiorrhiza Radix induced marked cell cycle arrest and apoptosis in PC-3 cells through the generation of intracellular reactive oxygen species. It was also demonstrated that oral administration of the acetonitrile extract of S. miltiorrhiza Radix decreased the incidence and growth of PC-3 tumor xenografts in nude mice. The results of the present study suggest that the acetonitrile extract of S. miltiorrhiza Radix exhibits marked inhibitory effects on the growth of prostate cancer cells in vitro and in vivo.

  8. Moringa Oleifera aqueous leaf extract down-regulates nuclear factor-kappaB and increases cytotoxic effect of chemotherapy in pancreatic cancer cells.

    Science.gov (United States)

    Berkovich, Liron; Earon, Gideon; Ron, Ilan; Rimmon, Adam; Vexler, Akiva; Lev-Ari, Shahar

    2013-08-19

    Fewer than 6% patients with adenocarcinoma of the pancreas live up to five years after diagnosis. Chemotherapy is currently the standard treatment, however, these tumors often develop drug resistance over time. Agents for increasing the cytotoxic effects of chemotherapy or reducing the cancer cells' chemo-resistance to the drugs are required to improve treatment outcome. Nuclear factor kappa B (NF-kB), a pro-inflammatory transcription factor, reportedly plays a significant role in the resistance of pancreatic cancer cells to apoptosis-based chemotherapy. This study investigated the effect of aqueous Moringa Oleifera leaf extract on cultured human pancreatic cancer cells - Panc-1, p34, and COLO 357, and whether it can potentiates the effect of cisplatin chemotherapy on these cells. The effect of Moringa Oleifera leaf extract alone and in combination with cisplatin on the survival of cultured human pancreatic cancer cells was evaluated by XTT-based colorimetric assay. The distribution of Panc-1 cells in the cell cycle following treatment with Moringa leaf extract was evaluated by flow cytometry, and evaluations of protein levels were via immunoblotting. Data of cell survival following combined treatments were analyzed with Calcusyn software. Moringa Oleifera leaf extract inhibited the growth of all pancreatic cell lines tested. This effect was significant in all cells following exposure to ≥0.75 mg/ml of the extract. Exposure of Panc-1 cells to Moringa leaf extract induced an elevation in the sub-G1 cell population of the cell-cycle, and reduced the expression of p65, p-IkBα and IkBα proteins in crude cell extracts. Lastly, Moringa Oleifera leaf extract synergistically enhanced the cytotoxic effect of cisplatin on Panc-1 cells. Moringa Oleifera leaf extract inhibits the growth of pancreatic cancer cells, the cells NF-κB signaling pathway, and increases the efficacy of chemotherapy in human pancreatic cancer cells.

  9. Aqueous Extract of Terminalia chebula Induces Apoptosis in Lung Cancer Cells Via a Mechanism Involving Mitochondria-mediated Pathways

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    Meiling Wang

    2015-04-01

    Full Text Available The current study was designed to evaluate the aqueous extract of Terminalia chebula activity, and the main pathway was detected on lung cancer by extracts of T. chebula. Aqueous extract of T. chebula was separated using a zeolite, and five fractions of T. chebula extract were obtained and analyzed by ultraviolet (UV and infrared (IR spectroscopy. Antiproliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT methods against human lung cancer (A549 and mouse lung cancer cell line LLC. T. chebula acts by regulating the Bcl-2 family protein-mediated mitochondrial pathway detected by western blot. Fraction 4 of the T. chebula extract showed much function and was thus studied further. Fraction 4 increased the activation of caspase-3, induced PARP cleavage, and promoted cytochrome c release into the cytoplasm. These data suggest that T. chebula acts by regulating the Bcl-2 family protein-mediated mitochondrial pathway and provide evidence that T. chebula deserves further investigation as a natural agent for treating and preventing cancer.

  10. Antitumor effects of a water-soluble extract from Maitake (Grifola frondosa) on human gastric cancer cell lines.

    Science.gov (United States)

    Shomori, Kohei; Yamamoto, Mako; Arifuku, Ichiro; Teramachi, Kazuki; Ito, Hisao

    2009-09-01

    We investigated the effects of a water-soluble extract of Maitake (Grifola frondosa), a Japanese edible mushroom, on the proliferation and cell death of four human gastric cancer cell lines (TMK-1, MKN28, MKN45 and MKN74). The Maitake extract (ME) inhibited the proliferation of all four cell lines in a time-dependent manner. The inhibition was most pronounced in TMK-1 cells, which exhibited up to 90% inhibition after treatment with 10% ME for 3 days. Staining of ME-treated TMK-1 cells with Hoechst 33258 revealed increased numbers of nuclear condensations and apoptotic bodies. Induction of apoptosis was confirmed by fluorescence-activated cell sorting analyses. Western blot analyses of TMK-1 cells after ME treatment revealed increases in intracytoplasmic cytochrome c and cleavage of caspase-3 and poly(ADP-ribose) polymerase, but no expression of p21 or Bax. The caspase-3 protease activities in lysates of TMK-1 cells treated with 1% or 10% ME were about three times higher than those in control cells. The proliferation of TMK-1 cells was hardly affected by the caspase-3 inhibitor z-DEVD-fmk. Taken together, these results suggest that ME induces apoptosis of TMK-1 cells by caspase-3-dependent and -independent pathways, resulting in potential antitumor effects on gastric cancer.

  11. Effect of Methanolic Extract of Dandelion Roots on Cancer Cell Lines and AMP-Activated Protein Kinase Pathway

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    Gauhar Rehman

    2017-11-01

    Full Text Available Ethnomedicinal knowledge of plant-derived bioactives could help us in discovering new therapeutic compounds of great potential. Certainly, dandelion has been used in traditional ethno-medicinal systems (i.e., Chinese, Arabian, Indian, and Native American to treat different types of cancer. Though, dandelion is highly vigorous, but the potential mode of action is still unclear. In the current study, the antiproliferative activity of methanolic extracts of dandelion root (MEDr on cell viability of HepG2, MCF7, HCT116, and normal Hs27 was investigated. It was observed that MEDr (500 μg/mL drastically decreased the growth of HepG2 cell line, while the effect on MCF7 and HCT116 cell lines was less pronounced and no effect has been observed in Hs27 cell lines. The MEDr also enhanced the phosphorylation level of AMPK of HepG2 cells, which considered crucial in cancer treatment and other metabolic diseases. The AMPK activation by MEDr noticed in the current study has never been reported previously. The results regarding the number of apoptotic cells (HepG2 cells were in line with the cell viability test. The current observations clearly demonstrated the potency of MEDr against liver cancer with validation that dandelion could control AMPK and thus cancer in the treated cell lines.

  12. Inhibition of Human Cervical Cancer Cell Growth by Ethanolic Extract of Boerhaavia diffusa Linn. (Punarnava Root

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    Rakhi Srivastava

    2011-01-01

    Full Text Available In Indian traditional medicine, Boerhaavia diffusa (punarnava roots have been widely used for the treatment of dyspepsia, jaundice, enlargement of spleen, abdominal pain and as an anti-stress agent. Pharmacological evaluation of the crude ethanolic extract of B. diffusa roots has been shown to possess antiproliferative and immunomodulatory properties. The extract of B. diffusa was studied for anti-proliferative effects on the growth of HeLa cells and for its effect on cell cycle. Bio-assays of extracts from B. diffusa root showed that a methanol : chloroform fraction (BDF 5 had an antiproliferative effect on HeLa cells. After 48 h of exposure, this fraction at a concentration of 200 μg mL−1 significantly reduced cell proliferation with visible morphological changes in HeLa cells. Cell cycle analysis suggests that antiproliferative effect of BDF 5 could be due to inhibition of DNA synthesis in S-phase of cell cycle in HeLa cells, whereas no significant change in cell cycle was detected in control cells. The fraction BDF 5 caused cell death via apoptosis as evident from DNA fragmentation and caspase-9 activation. Thus the extract has potential to be evaluated in detail to assess the molecular mechanism-mediated anticancer activities of this plant.

  13. Methanolic extract of Boswellia serrata exhibits anti-cancer activities by targeting microsomal prostaglandin E synthase-1 in human colon cancer cells.

    Science.gov (United States)

    Ranjbarnejad, Tayebeh; Saidijam, Massoud; Moradkhani, Shirin; Najafi, Rezvan

    2017-07-01

    Colorectal cancer (CRC) is the most common cancer. A proper method to reduce mortality of CRC is chemoprevention to prevent initiation and promotion of intestinal tumorgenesis. One of the promising and developing chemopreventive agents is natural compounds found in plants. Frankincense, the resin extract from the Boswellia specious, has been used in traditional and modern medicine for treating various diseases with very minimal side effects. In the current study, we investigated the anti-cancer activity of methanolic extract of Boswellia serrata (B. serrata) on HT-29 human colon cancer cells. HT-29 cells were treated with different concentrations of B. serrata and cell viability was assessed by MTT assay. mRNA expression of microsomal prostaglandin E synthase-1 (mPGES-1), vascular endothelial growth factor (VEGF), C-X-C chemokine receptor type 4 (CXCR4), matrix metalloproteinase-2 (MMP-2), MMP-9 and hypoxia-inducible factor-1 (HIF-1) were examined by quantitative real-time PCR. Apoptosis was evaluated by the proportion of sub-G1 cells. Prostaglandin E2 (PGE2) level and caspase 3 activity were determined by ELISA assay. Tube formation potential and HT-29 cells migration were assessed using three-dimensional vessel formation assay and scratch test. B. serrata extract considerably decreased the expression of mPGES-1, VEGF, CXCR4, MMP-2, MMP-9 and HIF-1. The caspase 3 activity and percent of cells in sub-G1 phase were increased by B. serrata extract. Cell viability, PGE2 generation, in vitro tube formation and cell migration were decreased significantly in B. serrata-treated HT-29 compared to the control group. Our findings suggest that B. serrata extract inhibits proliferation, angiogenesis and migration and induces apoptosis in HT-29 cells by inhibiting of mPGES-1 and decreasing the PGE2 level and its downstream targets. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Mistletoe (Viscum album) extract targets Axl to suppress cell proliferation and overcome cisplatin- and erlotinib-resistance in non-small cell lung cancer cells.

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    Kim, Soyoung; Kim, Kyung-Chan; Lee, ChuHee

    2017-12-01

    Mistletoe extract of Visucm album extract (VAE) contains many biologically active components and has been reported to be not only a complementary and alternative medicine, but also a potent therapeutic agent for many types of cancer. In this study, we examined the effect of VAE on expression and activation of Axl and scrutinized the involvement of Axl in the anti-cancer activity of VAE in parental and chemo-resistant non-small cell lung cancer (NSCLC) cells. The levels of Axl protein and mRNA were determined by Western blot analysis and RT-PCR, respectively. Phosphorylation of Axl upon Gas6 stimulation was observed by Western blot analysis. For ectopic expression or gene silencing of Axl, the recombinant plasmid, pcDNA3-Axl, or specific siRNA targeting Axl were transfected into A549 and H460 cells using Lipofectamine 2000, respectively. The anti-cancer activity of mistletoe extract was examined against the parental cells and each of their cisplatin- or erlotinib-resistant cells using trypan blue exclusion assays and colony formation assay. The levels of Axl mRNA were also reduced by VAE treatment, implying the transcriptional downregulation of Axl expression by VAE. In addition, the phosphorylation of Axl protein upon its ligand, Gas6, stimulation was found to be abrogated by VAE. We next found cytotoxic effect of VAE on both the parental NSCLC cells and their variants which are resistant to cisplatin (A549/CisR and H460/CisR) or erlotinib (H460/ER and H1975/ER). Treatment of these cells with VAE caused a dose-dependent decrease of cell viability and clonogenicity. This anti-proliferative effect of VAE was attenuated in Axl-overexpressing cells, while it was augmented in cells transfected Axl specific siRNA. Next, we also found that in cisplatin-resistant cells and erlotinib-resistant cells, VAE treatment decreased Axl protein level, colonogenicity. The levels of several cell cycle regulator, p21 and apoptosis related protein, X-linked inhibitor of apoptosis, was

  15. Antiproliferative activity and induction of apoptosis by Annona muricata (Annonaceae) extract on human cancer cells.

    Science.gov (United States)

    Pieme, Constant Anatole; Kumar, Santosh Guru; Dongmo, Mireille Sylviane; Moukette, Bruno Moukette; Boyoum, Fabrice Fekam; Ngogang, Jeanne Yonkeu; Saxena, Ajit Kumar

    2014-12-24

    Annona muricata (A. muricata) is widely distributed in Asia, Africa and South America. Different parts of this plant are used to treat several diseases in Cameroon. The aim of this study is to determine the in vitro anti-proliferative effects and apoptotic events of A. muricata extracts on HL-60 cells as well as to quantify its phenols content. The cell viability was measured by using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay while the changes in morphology of HL-60 cells, membrane mitochondrial potential (MMP) and the cell cycle were used for assessment apoptosis induction. The results show that the concentration of phenols, flavonoids and flavonols in the extracts varied depending on the part of the plant. All the extracts tested inhibited the proliferation of HL-60 cells in a concentration dependent manner with IC50 varied from 6-49 μg/mL. The growth inhibition of the cells by extracts was associated with the disruption of MMP, reactive oxygen species (ROS) generation and the G0/G1 cell arrest. These findings suggest that the extracts from A. muricata have strong antiproliferation potential and can induce apoptosis through loss of MMP and G0/G1 phase cell arrest.

  16. Antioxidant and apoptotic effects of an aqueous extract of Urtica dioica on the MCF-7 human breast cancer cell line.

    Science.gov (United States)

    Fattahi, Sadegh; Ardekani, Ali Motevalizadeh; Zabihi, Ebrahim; Abedian, Zeinab; Mostafazadeh, Amrollah; Pourbagher, Roghayeh; Akhavan-Niaki, Haleh

    2013-01-01

    Breast cancer is the most prevalent cancer and one of the leading causes of death among women in the world. Plants and herbs may play an important role in complementary or alternative treatment. The aim of this study was to evaluate the antioxidant and anti-proliferative potential of Urtica dioica. The anti oxidant activity of an aqueous extract of Urtica dioica leaf was measured by MTT assay and the FRAP method while its anti-proliferative activity on the human breast cancer cell line (MCF-7) and fibroblasts isolated from foreskin tissue was evaluated using MTT assay. Mechanisms leading to apoptosis were also investigated at the molecular level by measuring the amount of anti and pro-apoptotic proteins and at the cellular level by studying DNA fragmentation and annexin V staining by flow cytometry. The aqueous extract of Urtica dioica showed antioxidant effects with a correlation coefficient of r(2)=0.997. Dose-dependent and anti-proliferative effects of the extract were observed only on MCF-7 cells after 72 hrs with an IC50 value of 2 mg/ml. This anti proliferative activity was associated with an increase of apoptosis as demonstrated by DNA fragmentation, the appearance of apoptotic cells in flow cytometry analysis and an increase of the amount of calpain 1, calpastatin, caspase 3, caspase 9, Bax and Bcl-2, all proteins involved in the apoptotic pathway. This is the first time such in vitro antiproliferative effect of aqueous extract of Urtica dioica leaf has been described for a breast cancer cell line. Our findings warrant further research on Urtica dioica as a potential chemotherapeutic agent for breast cancer.

  17. Cytotoxic Effects of Alcoholic Extract of Dorema Glabrum Seed on Cancerous Cells Viability

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    Maryam Bannazadeh Amirkhiz

    2013-08-01

    Full Text Available Purpose: In the present study cytotoxic effects of the alcoholic extract of Dorema Glabrum seed on viability of WEHI-164 cells, mouse Fibrosarcoma cell line and L929 normal cells were compared with the cytotoxic effects of Taxol (anticancer and apoptosis inducer drug. Methods: To find out the plant extract cytotoxic effects, MTT test and DNA fragmentation assay, the biochemical hallmark of apoptosis were performed on cultured and treated cells. Results: According to the findings the alcoholic extract of Dorema Glabrum seed can alter cells morphology and because of chromatin condensation and other changes they shrink and take a spherical shape, and lose their attachment too. So the plant extract inhibits cell growth albeit in a time and dose dependent manner and results in degradation of chromosomal DNA. Conclusion: Our data well established the anti-proliferative effect of methanolic extract of Dorema Glabrum seed and clearly showed that the plant extract can induce apoptosis and not necrosis in vitro, but the mechanism of its activities remained unknown. These results demonstrated that Dorema Glabrum seed might be a novel and attractive therapeutic candidate for tumor treatment in clinical practices.

  18. Inhibition of lung cancer cells A549 and H460 by curcuminoid extracts and nanoemulsions prepared from Curcuma longa Linnaeus.

    Science.gov (United States)

    Chang, Hong-Bin; Chen, Bing-Huei

    2015-01-01

    The objectives of this study were to explore the inhibition mechanism of lung cancer cells A549 and H460 by curcuminoid extracts and nanoemulsions prepared from Curcuma longa Linnaeus. In addition, human bronchus epithelial cell line BEAS-2B (normal cell) was selected for comparison. A high-performance liquid chromatography (HPLC) method was developed to separate and quantify the various curcuminoids in C. longa extract, including curcumin (1,714.5 μg/mL), demethoxycurcumin (1,147.4 μg/mL), and bisdemethoxycurcumin (190.2 μg/mL). A high-stability nanoemulsion composed of Tween 80, water, and curcuminoid extract was prepared, with mean particle size being 12.6 nm. The cell cycle was retarded at G2/M for both the curcuminoid extract and nanoemulsion treatments; however, the inhibition pathway may be different. H460 cells were more susceptible to apoptosis than A549 cells for both curcuminoid extract and nanoemulsion treatments. Growth of BEAS-2B remained unaffected for both the curcuminoid extract and nanoemulsion treatments, with a concentration range from 1 to 4 μg/mL. Also, the activities of caspase-3, caspase-8, and caspase-9 followed a dose-dependent increase for both A549 and H460 cells for both the treatments, accompanied by a dose-dependent increase in cytochrome C expression and a dose-dependent decrease in CDK1 expression. Interestingly, a dose-dependent increase in cyclin B expression was shown for A549 cells for both the treatments, while a reversed trend was found for H460 cells. Both mitochondria and death receptor pathways may be responsible for apoptosis of both A549 and H460 cells.

  19. Inhibition of lung cancer cells A549 and H460 by curcuminoid extracts and nanoemulsions prepared from Curcuma longa Linnaeus

    Science.gov (United States)

    Chang, Hong-Bin; Chen, Bing-Huei

    2015-01-01

    The objectives of this study were to explore the inhibition mechanism of lung cancer cells A549 and H460 by curcuminoid extracts and nanoemulsions prepared from Curcuma longa Linnaeus. In addition, human bronchus epithelial cell line BEAS-2B (normal cell) was selected for comparison. A high-performance liquid chromatography (HPLC) method was developed to separate and quantify the various curcuminoids in C. longa extract, including curcumin (1,714.5 μg/mL), demethoxycurcumin (1,147.4 μg/mL), and bisdemethoxycurcumin (190.2 μg/mL). A high-stability nanoemulsion composed of Tween 80, water, and curcuminoid extract was prepared, with mean particle size being 12.6 nm. The cell cycle was retarded at G2/M for both the curcuminoid extract and nanoemulsion treatments; however, the inhibition pathway may be different. H460 cells were more susceptible to apoptosis than A549 cells for both curcuminoid extract and nanoemulsion treatments. Growth of BEAS-2B remained unaffected for both the curcuminoid extract and nanoemulsion treatments, with a concentration range from 1 to 4 μg/mL. Also, the activities of caspase-3, caspase-8, and caspase-9 followed a dose-dependent increase for both A549 and H460 cells for both the treatments, accompanied by a dose-dependent increase in cytochrome C expression and a dose-dependent decrease in CDK1 expression. Interestingly, a dose-dependent increase in cyclin B expression was shown for A549 cells for both the treatments, while a reversed trend was found for H460 cells. Both mitochondria and death receptor pathways may be responsible for apoptosis of both A549 and H460 cells. PMID:26345201

  20. The extract of Hibiscus syriacus inducing apoptosis by activating p53 and AIF in human lung cancer cells.

    Science.gov (United States)

    Cheng, Yeung-Leung; Lee, Shih-Chun; Harn, Horng-Jyh; Huang, Hsin-Chieh; Chang, Wen-Liang

    2008-01-01

    Natural products including plants, microorganisms and marine life provide rich resources for anticancer drug discovery. The root bark of Hibiscus syriacus has been used as an antipyretic, anthelmintic and antifungal agent in Asia. The antiproliferative effects of H. syriacus on human lung cancer cells were evaluated with bio-assays. The apoptotic activity was detected by Hoechst 33342 DNA staining and annexin V staining. The expression of caspases, p53, apoptosis induced factor (AIF), Bcl-2 and Bax were evaluated with Western blotting. The in vivo anticancer activity was evaluated using A549-xenograft model. The acetone extract of H. syriacus (HS-AE) exhibited a better cytotoxic effect on lung cancer cells than its methanol extract (HS-ME) or water extract (HS-WE). The IC(50) values of HS-AE on A549 (adenocarcinoma), H209 (squamous cell carcinoma) or H661 (large cell carcinoma) lung cancer cells ranged from 14 to 22 microg/ml after 48 hours of treatment. After 48 hours of exposure, HS-AE (15 microg/ml) induced A549 cell apoptosis to 48 +/- 3.6% of the control. Using Western blotting, HS-AE appears to suppress the expression of p53 and AIF. The results of the in vivo study showed that HS-AE suppresses growth in A549 subcutaneous xenograft tumors. These results indicate that HS-AE exerts significant and dose-dependent antiproliferative effects on cancer cells in vitro and in vivo, which prompts us to further evaluate and elucidate the bioactive component(s) of H. syriacus.

  1. Hericium erinaceus (Lion's Mane) mushroom extracts inhibit metastasis of cancer cells to the lung in CT-26 colon cancer-tansplanted mice.

    Science.gov (United States)

    Kim, Sung Phil; Nam, Seok Hyun; Friedman, Mendel

    2013-05-22

    This study investigated the antimetastatic activity of four Hericium erinaceus edible mushroom extracts using CT-26 murine colon carcinoma cells as an indicator of inhibition of cell migration to the lung. Hot water (HWE) and microwaved 50% ethanol (MWE) extracts of H. erinaceus strongly elicited cancer cell death through apoptosis and inhibited metastasis of cancer cells to the lungs by 66% and 69%, respectively. HWE and MWE reduced the expression of matrix metalloproteinases MMP-2 and MMP-9 in cells and their activities in culture media. Urokinase-type plasminogen activator (u-PA), another extracellular matrix (ECM)-degrading proteinase, also showed decreased protein expression. In CT-26 cells, HWE and MWE down-regulated extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) phosphorylations. The reduced phosphorylations seem to cause reduction of activity of the MMPs, thereby blocking migration and invasion of cells. Dietary administration of HWE and MWE reduced the formation of tumor nodules in the lung by about 50% and 55%, respectively, and prevented increases in lung weight caused by cancer cell metastasis. These results demonstrate the effectiveness of HWE and MWE as beneficial antimetastatic agents, targeting their upstream signaling molecules for mediating the expression of the ECM-degrading proteinases. Acidic and alkaline extracts were not bioactive. Bioactivity seems to be related to composition. H. erinaceus edible mushrooms have the potential to serve as a health-promoting functional food.

  2. Antiproliferation and Induction of Apoptosis in Ca9-22 Oral Cancer Cells by Ethanolic Extract of Gracilaria tenuistipitata

    Directory of Open Access Journals (Sweden)

    Chi-Chen Yeh

    2012-09-01

    Full Text Available The water extract of Gracilaria tenuistipitata have been found to be protective against oxidative stress-induced cellular DNA damage, but the biological function of the ethanolic extracts of G. tenuistipitata (EEGT is still unknown. In this study, the effect of EEGT on oral squamous cell cancer (OSCC Ca9-22 cell line was examined in terms of the cell proliferation and oxidative stress responses. The cell viability of EEGT-treated OSCC cells was significantly reduced in a dose-response manner (p < 0.0001. The annexin V intensity and pan-caspase activity of EEGT-treated OSCC cells were significantly increased in a dose-response manner (p < 0.05 to 0.0001. EEGT significantly increased the reactive oxygen species (ROS level (p < 0.0001 and decreased the glutathione (GSH level (p < 0.01 in a dose-response manner. The mitochondrial membrane potential (MMP of EEGT-treated OSCC cells was significantly decreased in a dose-response manner (p < 0.005. In conclusion, we have demonstrated that EEGT induced the growth inhibition and apoptosis of OSCC cells, which was accompanied by ROS increase, GSH depletion, caspase activation, and mitochondrial depolarization. Therefore, EEGT may have potent antitumor effect against oral cancer cells.

  3. Anticancer activity and apoptosis inducing effect of methanolic extract of Cordia dichotoma against human cancer cell line

    Directory of Open Access Journals (Sweden)

    Md. Azizur Rahman

    2015-03-01

    Full Text Available MTT assay and DAPI staining test were performed to evaluate anticancer potential and to assess apoptosis inducing effect of methanolic extract of Cordia dichotoma leaves (MECD against human cervical cancer cell line (HeLa. Changes in MMP and intracellular ROS level were also assessed by JC-1 and DCFH-DA staining. Total phenolic contents were determined by colorimetric principle. Levels of statistical significance were determined by one-way analysis of variance followed by Dunnett’s posttest. Results showed that MECD with obtained IC50 of 202 µg/mL inhibited in vitro proliferation of human cervical cancer cells and induced apoptosis indicating its promising anticancer activity as compared to the standard tamoxifen with obtained IC50 of 48 µg/mL. Total phenolic contents was found to be 176.5 mg GAE/g dried extract. It was concluded that MECD possess promising anticancer activity and induce apoptosis.

  4. Concentration effects of grape seed extracts in anti-oral cancer cells involving differential apoptosis, oxidative stress, and DNA damage.

    Science.gov (United States)

    Yen, Ching-Yu; Hou, Ming-Feng; Yang, Zhi-Wen; Tang, Jen-Yang; Li, Kun-Tzu; Huang, Hurng-Wern; Huang, Yu-Hsuan; Lee, Sheng-Yang; Fu, Tzu-Fun; Hsieh, Che-Yu; Chen, Bing-Hung; Chang, Hsueh-Wei

    2015-03-29

    Grape seeds extract (GSE) is a famous health food supplement for its antioxidant property. Different concentrations of GSE may have different impacts on cellular oxidative/reduction homeostasis. Antiproliferative effect of GSE has been reported in many cancers but rarely in oral cancer. The aim of this study is to examine the antioral cancer effects of different concentrations of GSE in terms of cell viability, apoptosis, reactive oxygen species (ROS), mitochondrial function, and DNA damage. High concentrations (50-400 μg/ml) of GSE dose-responsively inhibited proliferation of oral cancer Ca9-22 cells but low concentrations (1-10 μg/ml) of GSE showed a mild effect in a MTS assay. For apoptosis analyses, subG1 population and annexin V intensity in high concentrations of GSE-treated Ca9-22 cells was increased but less so at low concentrations. ROS generation and mitochondrial depolarization increased dose-responsively at high concentrations but showed minor changes at low concentrations of GSE in Ca9-22 cells. Additionally, high concentrations of GSE dose-responsively induced more γH2AX-based DNA damage than low concentrations. Differential concentrations of GSE may have a differentially antiproliferative function against oral cancer cells via differential apoptosis, oxidative stress and DNA damage.

  5. Evaluation of chemical composition, antioxidant, antibacterial, cytotoxic and apoptotic effects of Aloysia citrodora extract on colon cancer cell line

    Directory of Open Access Journals (Sweden)

    Amir Mirzaie

    2016-06-01

    Full Text Available Background: Aloysia citrodora belongs to the Verbenaceae family of plants, a well-known herbal medicine in Iran. The aim of the present study was to investigate the chemical composition, antioxidant, antibacterial, cytotoxic and apoptotic effect of A. citrodora extract against human colon cancer (HT29 cells by using real-time polymerase chain reaction and flow-cytometry methods. Methods: This experimental study was carried out in Islamic Azad University, East Tehran Branch, from March to September of 2014. At first, the A. citrodora chemical constituents were analyzed by gas chromatography-mass spectrometry (GC-MS technique. In addition, antioxidant assay, antibacterial and anti-cancer effect was performed using 1,1-diphenyl-2-picrylhydrazyl (DPPH, disk diffusion and 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT methods, respectively. The half maximal inhibitory concentration (IC50 value was calculated. We extracted total RNA molecules by using RNX solution, after which cDNA was synthesized. Finally, the pro-apoptotic (Bax and anti-apoptotic (Bcl2 gene expression was performed by real-time polymerase chain reaction and apoptotic effects were analyzed using Flow-cytometry method. Results: GC-MS analysis of Aloysia citrodora extract was shown 37 major components and the most frequent component was belonged to Spathulenol (17.57% and Caryophyllene oxide (15.15% The antioxidant activity of the extract was IC50= 0.6±0.03 mg/ml. The maximum and minimum antibacterial effects of extract were belonged to gram-negative and gram-positive bacteria, respectively. Cytotoxic results revealed that the A.citrodora extract have IC50= 20.1±0.78 mg/ml against colon cancer (HT29 cell line and real-time polymerase chain reaction results showed the expression level of Bax and Bcl2 was increased and decreased respectively in colon cancer cell line (3.470±0.72 (P< 0.05, 0.43±0.35 (P< 0.05. In addition, the flow-cytometry results indicated the 38

  6. Evaluation of chemical composition, antioxidant, antibacterial, cytotoxic and apoptotic effects of Aloysia citrodora extract on colon cancer cell line

    OpenAIRE

    Amir Mirzaie; Seyed Ataollah Sadat Shandiz; Hassan Noorbazargan; Elahe Ali Asgary

    2016-01-01

    Background: Aloysia citrodora belongs to the Verbenaceae family of plants, a well-known herbal medicine in Iran. The aim of the present study was to investigate the chemical composition, antioxidant, antibacterial, cytotoxic and apoptotic effect of A. citrodora extract against human colon cancer (HT29) cells by using real-time polymerase chain reaction and flow-cytometry methods. Methods: This experimental study was carried out in Islamic Azad University, East Tehran Branch, from March to...

  7. Inhibitory effect of ethyl acetate extract of the shaggy inc cap medicinal mushroom, Coprinus comatus (Higher Basidiomycetes) fruit bodies on cell growth of human ovarian cancer.

    Science.gov (United States)

    Rouhana-Toubi, Amal; Wasser, Solomon P; Agbarya, Abed; Fares, Fuad

    2013-01-01

    In a previous study, we screened organic extracts of different mushroom mycelia and picked ethyl acetate extract of Coprinus comatus as one of the most active extracts against human ovarian cancer cells. In the current study, we extracted a dry powder of C. comatus fruit bodies using ethyl acetate and examined its effect on the viability of three cell lines originated from human ovarian cancer (ES-2, SKOV-3, and SW-626). This extract was active against all tested cell lines, in a dose-dependent manner (concentrations 50-200 µg/mL, P<0.01). In an attempt to segregate the active fraction, we subjected the extract to chromatography on a silica gel column. The effect of six different fractions and of the crude extract on the viability of ES-2 cells was examined after exposure time of 24 h. Fraction F (last eluted) was significantly more effective than crude extract in the reduction of cell viability (P<0.01). Fraction F was also significantly more active than crude extract in the reduction of viability of SKOV-3 cells. We next identified some of the compounds of fraction F (mainly fatty acids) by gas chromatography-mass spectrometry. In summary, ethyl acetate extract of C. comatus reduced viability of three lines of human ovarian cancer. Fractionation of this extract by a silica gel column enabled the selection of a fraction significantly more active than the original extract.

  8. Cytotoxicity of blended versus single medicinal mushroom extracts on human cancer cell lines: contribution of polyphenol and polysaccharide content.

    Science.gov (United States)

    Durgo, Ksenija; Koncar, Mladen; Komes, Drazenka; Belscak-Cvitanovic, Ana; Franekic, Jasna; Jakopovich, Ivan; Jakopovich, Neven; Jakopovich, Boris

    2013-01-01

    The use of mushrooms contributes to human nutrition by providing low lipid content of lipids and high dietary fiber content, as well as significant content of other biologically active compounds such as polysaccharides, minerals, vitamins, and polyphenolic antioxidants. This study aimed to determine the content of polyphenols and polysaccharides, as well as the cytotoxic and antioxidative properties of several medicinal mushroom preparations. The content of total phenols and flavonoids of preparations of blended mushroom extracts (Lentifom, Super Polyporin, Agarikon, Agarikon Plus, Agarikon.1, and Mykoprotect.1) was evaluated quantitatively by using ultraviolet-visible spectroscopy spectrophotometric methods. The antioxidant capacity of the preparations was evaluated using the ABTS (2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and ferric reducing/antioxidant power assays. The content of water-soluble polysaccharides was determined using a specific gravimetric method, based on ethanol precipitation. To determine cytotoxic effects of single and blended mushroom extracts, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and neutral red assays were conducted using human small cell lung cancer, lung adenocarcinoma, colon cancer, and brain astrocytoma cancer cells. The obtained results suggest that due to the significant content of beneficial polyphenolic antioxidants and soluble polysaccharides, use of these mushroom preparations is beneficial in maintaining good health, as well as in the prevention and adjuvant biotherapy of various human pathological aberrations. These results reveal that these extracts exhibit different cytotoxic effects on tumor cells originating from different tissues. In addition, the comparison of investigated blended mushroom extracts with three well-known commercial mushroom products derived from single mushroom species or single mushroom compounds shows that blended mushroom extracts exhibit significantly stronger

  9. Muscadine grape skin extract reverts snail-mediated epithelial mesenchymal transition via superoxide species in human prostate cancer cells.

    Science.gov (United States)

    Burton, Liza J; Barnett, Petrina; Smith, Basil; Arnold, Rebecca S; Hudson, Tamaro; Kundu, Kousik; Murthy, Niren; Odero-Marah, Valerie A

    2014-03-12

    Snail transcription factor can induce epithelial-mesenchymal transition (EMT), associated with decreased cell adhesion-associated molecules like E-cadherin, increased mesenchymal markers like vimentin, leading to increased motility, invasion and metastasis. Muscadine grape skin extract (MSKE) has been shown to inhibit prostate cancer cell growth and induce apoptosis without affecting normal prostate epithelial cells. We investigated novel molecular mechanisms by which Snail promotes EMT in prostate cancer cells via Reactive Oxygen Species (ROS) and whether it can be antagonized by MSKE. ARCaP and LNCaP cells overexpressing Snail were utilized to examine levels of reactive oxygen species (ROS), specifically, superoxide, in vitro using Dihydroethidium (DHE) or HydroCy3 dyes. Mitosox staining was performed to determine whether the source of ROS was mitochondrial in origin. We also investigated the effect of Muscadine grape skin extract (MSKE) on EMT marker expression by western blot analysis. Migration and cell viability using MTS proliferation assay was performed following MSKE treatments. Snail overexpression in ARCaP and LNCaP cells was associated with increased concentration of mitochondrial superoxide, in vitro. Interestingly, MSKE decreased superoxide levels in ARCaP and LNCaP cells. Additionally, MSKE and Superoxide Dismutase (SOD) reverted EMT as evidenced by decreased vimentin levels and re-induction of E-cadherin expression in ARCaP-Snail cells after 3 days, concomitant with reduced cell migration. MSKE also decreased Stat-3 activity in ARCaP-Snail cells. This study shows that superoxide species may play a role in Snail transcription factor-mediated EMT. Therefore, therapeutic targeting of Snail with various antioxidants such as MSKE may prove beneficial in abrogating EMT and ROS-mediated tumor progression in human prostate cancer.

  10. Anticancer Screening of Various Seed Extract of Cardiospermum halicacabum on Human Colorectal, Skin and Breast Cancer Cell Lines

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    Behzad Mohaddesi

    2015-08-01

    Full Text Available Background: In the modern lifestyle, the increase in cancer and related chronic disorders is a major public health problem. In spite of different methods used for the treatment of these conditions, natural medicines have high demands due to their significant effects as immune enhancement and therapeutic agents and fewer side effects in comparison with other treatment methods. Hence, this study was undertaken to evaluate the cytotoxic effect of cardiospermum halicacabum Linn. seeds, based on traditional claims.Methods: A Soxhlet extractor was used to obtain different extracts from seeds of C. halicacabum Linn. Sulforhodamine B colorimetric (SRB assay used for the evaluation of the cytotoxic effect of the various extracts on HT-29, HCT-15 colon carcinoma, SK-MEL-2 skin carcinoma, and MCF-7 breast carcinoma. The results were compared against Doxorubicin as a standard drug.Results: The results of the present study showed the potent cytotoxic activity of n-hexane extract of seeds of C. halicacabum Linn. against the MCF-7 breast cancer cell line with 50% growth inhibition value (GI50 of 12.8 μg/ml but other extracts showed poor activity in other tested cell lines.Conclusions: The results indicated the potential medicinal value of C. halicacabum Linn. seeds oil with the highest extractive yield as an antineoplastic agent. However, further studies are needed for the isolation of the active anticancer compounds and evaluating the mechanism of action of the responsible compound.

  11. Oxidative Stress-Mediated Apoptosis Induced by Ethanolic Mango Seed Extract in Cultured Estrogen Receptor Positive Breast Cancer MCF-7 Cells

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    Al-Shwyeh Hussah Abdullah

    2015-02-01

    Full Text Available Breast cancer has become a global health issue requiring huge expenditures for care and treatment of patients. There is a need to discover newer cost-effective alternatives for current therapeutic regimes. Mango kernel is a waste product with potential as a source of anti-cancer phytochemicals, especially since it is non-toxic towards normal breast cell lines at concentrations for which it induces cell death in breast cancer cells. In this study, the anti-cancer effect of mango kernel extract was determined on estrogen receptor-positive human breast carcinoma (MCF-7 cells. The MCF-7 cells were cultured and treated with 5, 10 and 50 μg/mL of mango kernel extract for 12 and 24 h. In response to treatment, there were time- and dose-dependent increases in oxidative stress markers and pro-apoptotic factors; Bcl-2-like protein 4 (BAX, p53, cytochrome c and caspases (7, 8 and 9 in the MCF-7 cells treated with the extract. At the same time, there were decreases in pro-survival markers (Bcl-2 and glutathione as the result of the treatments. The changes induced in the MCF-7 cells by mango kernel extract treatment suggest that the extract can induce cancer cell apoptosis, likely via the activation of oxidative stress. These findings need to be evaluated further to determine whether mango kernel extract can be developed as an anti-breast cancer agent.

  12. Oxidative stress-mediated apoptosis induced by ethanolic mango seed extract in cultured estrogen receptor positive breast cancer MCF-7 cells.

    Science.gov (United States)

    Abdullah, Al-Shwyeh Hussah; Mohammed, Abdulkarim Sabo; Rasedee, Abdullah; Mirghani, Mohamed Elwathig Saeed

    2015-02-05

    Breast cancer has become a global health issue requiring huge expenditures for care and treatment of patients. There is a need to discover newer cost-effective alternatives for current therapeutic regimes. Mango kernel is a waste product with potential as a source of anti-cancer phytochemicals, especially since it is non-toxic towards normal breast cell lines at concentrations for which it induces cell death in breast cancer cells. In this study, the anti-cancer effect of mango kernel extract was determined on estrogen receptor-positive human breast carcinoma (MCF-7) cells. The MCF-7 cells were cultured and treated with 5, 10 and 50 μg/mL of mango kernel extract for 12 and 24 h. In response to treatment, there were time- and dose-dependent increases in oxidative stress markers and pro-apoptotic factors; Bcl-2-like protein 4 (BAX), p53, cytochrome c and caspases (7, 8 and 9) in the MCF-7 cells treated with the extract. At the same time, there were decreases in pro-survival markers (Bcl-2 and glutathione) as the result of the treatments. The changes induced in the MCF-7 cells by mango kernel extract treatment suggest that the extract can induce cancer cell apoptosis, likely via the activation of oxidative stress. These findings need to be evaluated further to determine whether mango kernel extract can be developed as an anti-breast cancer agent.

  13. In vitro cytotoxicity of crude alkaloidal extracts of South African Menispermaceae against three cancer cell lines

    CSIR Research Space (South Africa)

    De Wet, H

    2009-07-20

    Full Text Available -35-9026491. species, although species from five genera in this family are used in cancer treatment (De Wet, 2006) in other parts of the world. These genera are Cissampelos, Sphe- nocentrum, Menispermum, Stephania and Tinospora, and were used in treating stomach... recorded (published) history of use against stomach and skin cancer in South Africa (Van Wyk and Gericke, 2000), but no screening for cytotoxicity against cancer cell lines has been reported on any of the 13 South African spe- cies. Most...

  14. Cytotoxicity and Proteasome Inhibition by Alkaloid Extract from Murraya koenigii Leaves in Breast Cancer Cells-Molecular Docking Studies.

    Science.gov (United States)

    Ismail, Ayesha; Noolu, Bindu; Gogulothu, Ramesh; Perugu, Shyam; Rajanna, Ajumeera; Babu, Suresh K

    2016-12-01

    Murraya koenigii (curry tree) leaves are rich in bioactive compounds such as flavonoids, alkaloids, and coumarins. Alkaloids from M. koenigii leaves have antianalgesic, antiulcerogenic, antiobesity, and antitumor activities. In this study, we tested the cytotoxic and proteasome-inhibitory potential of a total alkaloid extract (TAE) from M. koenigii leaves in the breast cancer cell line MDA-MB-231. The TAE decreased cell viability with an IC 50 of 14.4 μg/mL and altered growth kinetics of breast cancer cells. TAE (32 μg/mL) arrested cells (35%) in the "S" phase of the cell cycle and induced apoptosis. The 26S proteasome, a multicatalytic protease complex, promotes tumor cell proliferation and protects tumor cells from apoptosis. The TAE and mahanine, a carbazole alkaloid present in M. koenigii leaves, preferentially inhibited the trypsin-like, but not the chymotrypsin-like proteolytic activity of the proteasome with an IC 50 of 162 μg/mL and 287 μM, respectively. In silico analysis of 26 compounds from M. koenigii leaves revealed significant docking scores for mahanine and two other carbazole alkaloids with the β2 and β5 subunits of the catalytic 20S proteasome. Taken together, this study demonstrates that inhibition of the proteasome is an important biological activity of M. koenigii alkaloids, which may lead to cancer cell death.

  15. Cytotoxicity and Proapoptotic Effects of Allium atroviolaceum Flower Extract by Modulating Cell Cycle Arrest and Caspase-Dependent and p53-Independent Pathway in Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Somayeh Khazaei

    2017-01-01

    Full Text Available Breast cancer is the second leading cause of cancer death among women and despite significant advances in therapy, it remains a critical health problem worldwide. Allium atroviolaceum is an herbaceous plant, with limited information about the therapeutic capability. We aimed to study the anticancer effect of flower extract and the mechanisms of action in MCF-7 and MDA-MB-231. The extract inhibits the proliferation of the cells in a time- and dose-dependent manner. The underlying mechanism involved the stimulation of S and G2/M phase arrest in MCF-7 and S phase arrest in MDA-MB-231 associated with decreased level of Cdk1, in a p53-independent pathway. Furthermore, the extract induces apoptosis in both cell lines, as indicated by the percentage of sub-G0 population, the morphological changes observed by phase contrast and fluorescent microscopy, and increase in Annexin-V-positive cells. The apoptosis induction was related to downregulation of Bcl-2 and also likely to be caspase-dependent. Moreover, the combination of the extract and tamoxifen exhibits synergistic effect, suggesting that it can complement current chemotherapy. LC-MS analysis displayed 17 major compounds in the extract which might be responsible for the observed effects. Overall, this study demonstrates the potential applications of Allium atroviolaceum extract as an anticancer drug for breast cancer treatment.

  16. Cationic Antimicrobial Peptides Derived from Crocodylus siamensis Leukocyte Extract, Revealing Anticancer Activity and Apoptotic Induction on Human Cervical Cancer Cells.

    Science.gov (United States)

    Theansungnoen, Tinnakorn; Maijaroen, Surachai; Jangpromma, Nisachon; Yaraksa, Nualyai; Daduang, Sakda; Temsiripong, Theeranan; Daduang, Jureerut; Klaynongsruang, Sompong

    2016-06-01

    Known antimicrobial peptides KT2 and RT2 as well as the novel RP9 derived from the leukocyte extract of the freshwater crocodile (Crocodylus siamensis) were used to evaluate the ability in killing human cervical cancer cells. RP9 in the extract was purified by a combination of anion exchange column and reversed-phase HPLC, and its sequence was analyzed by mass spectrometry. The novel peptide could inhibit Gram-negative Vibrio cholerae (clinical isolation) and Gram-positive Bacillus pumilus TISTR 905, and its MIC values were 61.2 µM. From scanning electron microscopy, the peptide was seen to affect bacterial surfaces directly. KT2 and RT2, which are designed antimicrobial peptides using the C. siamensis Leucrocin I template, as well as RP9 were chemically synthesized for investigation of anticancer activity. By Sulforhodamine B colorimetric assay, these antimicrobial peptides could inhibit both HeLa and CaSki cancer cell lines. The IC50 values of KT2 and RT2 for HeLa and CaSki cells showed 28.7-53.4 and 17.3-30.8 µM, while those of RP9 were 126.2 and 168.3 µM, respectively. Additionally, the best candidate peptides KT2 and RT2 were used to determine the apoptotic induction on cancer cells by human apoptosis array assay. As a result, KT2 and RT2 were observed to induce apoptotic cell death in HeLa cells. Therefore, these results indicate that KT2 and RT2 with antimicrobial activity have a highly potent ability to kill human cervical cancer cells.

  17. Acceleration of pro-caspase-3 maturation and cell migration inhibition in human breast cancer cells by phytoconstituents of Rheum emodi rhizome extracts.

    Science.gov (United States)

    Naveen Kumar, D R; George, V Cijo; Suresh, P K; Kumar, R Ashok

    2013-01-01

    The aggressive nature of estrogen receptor (ER)-negative breast cancer subtype obligates for innovative targeted therapies. The present study aimed to investigate the phytoconstituents and specific anticancer activities of Rheum emodi rhizome, a known food source used locally to treat various ailments. Petroleum ether extracts (hot [PHR] and cold [PCR]) of R. emodi, exhibited significant free radical scavenging potentials through DPPH and reducing power assays, rendering them as good sources of antioxidants. The extracts, PHR and PCR had shown significant (P < 0.05) cancer-cell-specific cytotoxicity in the assayed cells (MDA-MB-231 [breast carcinoma] and WRL-68 [non-tumoral]) at 100 μg/ml, and 50 and 100 μg/ml concentrations respectively. Extracts also induced fervent apoptosis in ER-negative cells (MDA-MB-231) compared to ER-positive subtype (MCF-7), and found to involve CPP32/caspase-3 in its apoptosis induction mechanism. Moreover, extracts had an inevitable potential to inhibit the migration of metastatic breast cancer cells (MDA-MB-231) in vitro. Further, the active principles of extracts were identified through HPLC and GC-MS analysis to reveal major polyphenolics, 4,7-Dimethyl-(octahydro)indolo[4,3-fg]quinolin-10-one, 5-Oxo-isolongifolene, Valencene-2, and other quinone, quinoline and anthraquinone derivatives. The extracts are thus good candidates to target malignant ER-negative breast cancer, and the identified phytoconstituents could be eluted in further exploratory studies for use in dietary-based anti-breast cancer therapies.

  18. Hexane extract of Raphanus sativus L. roots inhibits cell proliferation and induces apoptosis in human cancer cells by modulating genes related to apoptotic pathway.

    Science.gov (United States)

    Beevi, Syed Sultan; Mangamoori, Lakshmi Narasu; Subathra, Murugan; Edula, Jyotheeswara Reddy

    2010-09-01

    Raphanus sativus, a common cruciferous vegetable has been attributed to possess a number of pharmacological and therapeutic properties. It has been used in indigenous system of medicine for the treatment of various human ailments in India. This present study evaluated the chemopreventive efficacy of different parts of R. sativus such as root, stem and leaves, extracted with solvents of varying polarity and investigated the molecular mechanism leading to growth arrest and apoptotic cell death in human cancer cell lines. Of the different parts, significant growth inhibitory effect was observed with hexane extract of R. sativus root. Analysis of hexane extract by GC-MS revealed the presence of several isothiocyanates (ITCs) such as 4-(methylthio)-3-butenyl isothiocyanate (MTBITC), 4-(methylthio)-3-butyl isothiocyanate (erucin), 4-methylpentyl isothiocyanate, 4-pentenyl isothiocyanate and sulforaphene. R. sativus root extract induced cell death both in p53 proficient and p53 deficient cell lines through induction of apoptotic signaling pathway regardless of the p53 status of cells. The molecular mechanisms underlying R. sativus-induced apoptosis may involve interactions among Bcl(2) family genes, as evidenced by up-regulation of pro-apoptotic genes and down-regulation of anti-apoptotic genes along with activation of Caspase-3. Our findings present the first evidence that hexane extract of R. sativus root exerts potential chemopreventive efficacy and induces apoptosis in cancer cell lines through modulation of genes involved in apoptotic signaling pathway.

  19. Cytotoxicity Studies of the Extracts, Fractions, and Isolated Compound of Pseudocedrela kotschyi on Cervical Cancer (HeLa), Breast Cancer (MCF-7) and Skeletal Muscle Cancer (RD) Cells.

    Science.gov (United States)

    Elufioye, Taiwo O; Abdul, Abolaji A; Moody, Jone O

    2017-01-01

    This study determined the cytotoxic effects of root and stem bark extracts, fractions, and isolated compounds derived from Pseudocedrela kotschyi on HeLa, MCF-7, and RD cells. The cytotoxic activity was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay against three cell lines (RD, HeLa, and MCF 7) at concentrations ranging from 0.01 to 1000 μg/mL. Isolation of crude saponin was done from the most active ethyl acetate fraction and further purified using vacuum liquid chromatography and preparative thin layer chromatographic techniques. The cytotoxicity assay revealed that the methanol extract from the root bark and the ethyl acetate fraction from the stem bark exhibited marked anticancer activity with IC50 of 87.36 μg/ml and 21.53 μg/ml, respectively, on HeLa cancer cell line and 101.51 μg/mL and 38.46 μg/mL, respectively, on RD cell line. These values are comparable with that obtained from vinblastine and methotrexate used as standard drugs (IC50 values of 0.01 μg/mL and 0.05 μg/mL, respectively). The isolated crude saponins also gave IC50 values of 5.28 μg/mL and 81.52 μg/mL against the RD cell lines and IC50values of 1.05 μg/mL and 86.8 μg/mL for the MCF 7 cancer cell lines. PTLC led to the isolation of a compound from the crude saponin which was identified as 7-deacetoxy-7-oxogedunin through spectroscopic analysis and comparison with literature data. P. kotschyi could be considered as a potential source of chemotherapeutic agent. However, further research to determine the exact mechanism of action needs to be carried out. Pseudocedrela kotschyi methanol extract from the root bark and the ethyl acetate fraction from the stem bark exhibited marked anticancer activity on HeLa, MCF-7, and RD cell lines7-deacetoxy-7-oxogedunin isolated as a white crystalline substance from the most active ethyl acetate fraction contributed to the observed activity. Abbreviations Used: MTT: 3-(4,5-dimethylthiazol-2-yl)-2

  20. In Vivo Inhibition of Proteasome Activity and Tumour Growth by Murraya koenigii Leaf Extract in Breast Cancer Xenografts and by Its Active Flavonoids in Breast Cancer Cells.

    Science.gov (United States)

    Noolu, Bindu; Gogulothu, Ramesh; Bhat, Mehrajuddin; Qadri, Syed S Y H; Reddy, V Sudhakar; Reddy, G Bhanuprakash; Ismail, Ayesha

    2016-01-01

    Inhibition of the 26S proteasome is an attractive approach for anticancer therapy. Proteasome inhibitors are known to selectively target cancer cells and make them more sensitive to chemotherapeutic agents. Murraya koenigii is a medicinally important herb of Asian origin and a rich source of bioactive compounds such as flavonoids and alkaloids. In the present study, we investigated the proteasome inhibitory and apoptotic effect of M. koenigii leaf extract in vivo in a xenograft tumor mouse model, and also assessed the toxicity if any in normal mice. M. koenigii extract did not lead to any toxicity in mice. Analysis of extract revealed the presence of flavonoid compounds which act as proteasome inhibitors. Quercetin treatment led to the decrease in the cell viability and arrest of cells in G2/M phase. Quercetin, Apigenin, Kaempferol and Rutin; flavonoids present in the leaf extract, dose-dependently inhibited the endogenous 26S proteasome activity in MDA-MB-231 cells. Reduction in tumor growth was associated with a decrease in proteasomal enzyme activities in the treated groups. Increased caspase-3 activity and TUNEL-positive cells indicated enhanced apoptosis with Murraya leaf extract treatment. Decreased expression of angiogenic and anti-apoptotic gene markers is indicative of inhibition of angiogenesis and promotion of apoptosis in the leaf extract treated tumors.

  1. The aqueous extract of Brucea javanica suppresses cell growth and alleviates tumorigenesis of human lung cancer cells by targeting mutated epidermal growth factor receptor

    Directory of Open Access Journals (Sweden)

    Kim SH

    2016-11-01

    Full Text Available Seung-Hun Kim,1,* Chun-Yen Liu,1,* Po-Wei Fan,1 Chang-Heng Hsieh,1 Hsuan-Yuan Lin,1 Ming-Chung Lee,2 Kang Fang1 1Department of Life Science, National Taiwan Normal University, Taipei, 2Brion Research Institute of Taiwan, New Taipei City, Taiwan *These authors contributed equally to this work Abstract: As a practical and safe herbal medicine, the seeds of Brucea javanica (L. Merr., were used to cure patients suffering from infectious diseases such as malaria. Recent advances revealed that the herb could also be a useful cancer therapy agent. The study demonstrated that aqueous B. javanica (BJ extract attenuated the growth of human non-small-lung cancer cells bearing mutant L858R/T790M epidermal growth factor receptor (EGFR. The reduced cell viability in H1975 cells was attributed to apoptosis. Transfection of EGFR small hairpin RNA reverted the sensitivities. When nude mice were fed BJ extract, the growth of xenograft tumors, as established by H1975 cells, was suppressed. Additional histological examination and fluorescence analysis of the resected tissues proved that the induced apoptosis mitigated tumor growth. The work proved that the BJ extract exerted its effectiveness by targeting lung cancer cells carrying mutated EGFR while alleviating tumorigenesis. Aqueous BJ extract is a good candidate to overcome drug resistance in patients undergoing target therapy. Keywords: Brucea javanica, target therapy, epidermal growth factor receptor, human lung, herbal medicine, apoptosis

  2. Functional proteomic analysis revels that the ethanol extract of Annona muricata L. induces liver cancer cell apoptosis through endoplasmic reticulum stress pathway.

    Science.gov (United States)

    Liu, Na; Yang, Hua Li; Wang, Pu; Lu, Yu Cheng; Yang, Ying Juan; Wang, Lan; Lee, Shao Chin

    2016-08-02

    Annona muricata L. is used to treat cancer in some countries. Extracts of Annona muricata have been shown to cause apoptosis of various cancer cells in vitro, and inhibit tumor growth in vivo in animal models. However, the molecular mechanisms underlying its anti-cancer and apoptotic effects of the herb remain to be explored. The study investigated the molecular mechanisms underlying liver cancer cell apoptosis triggered by the ethanol extract of leaves of Annona muricata L. Liver cancer HepG2 cells were used as experimental model. MTT assay was employed to evaluate cell viability. Flow cytometry and TUNEL assays were performed to confirm apoptosis. We employed functional proteomic analysis to delineate molecular pathways underlying apoptosis triggered by the herbal extract. We showed that the extract was able to reduce viability and trigger apoptosis of the cancer cells. Proteomic analysis identified 14 proteins associated with the extract-elicited apoptosis, which included the increased expression levels of HSP70, GRP94 and DPI-related protein 5. Western blot analysis confirmed that the extract did up-regulated the protein levels of HSP70 and GRP94. Results from bioinformatic annotation pulled out two molecular pathways for the extract, which, notably, included endoplasmic reticulum (ER) stress which was evidenced by the up-regulation of HSP70, GRP94 and PDI-related protein 5. Further examinations of typical protein signaling events in ER stress using western blot analysis have shown that the extract up-regulated the phorsphorelation of PERK and eIF2α as well as the expression level of Bip and CHOP. Our results indicate that the ethanol extract of leaves of Annona muricata L. causes apoptosis of liver cancer cells through ER stress pathway, which supports the ethnomedicinal use of this herb as an alternative or complementary therapy for cancer. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  3. Hazelnut (Corylus avellana L. Shells Extract: Phenolic Composition, Antioxidant Effect and Cytotoxic Activity on Human Cancer Cell Lines

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    Tiziana Esposito

    2017-02-01

    Full Text Available Hazelnut shells, a by-product of the kernel industry processing, are reported to contain high amount of polyphenols. However, studies on the chemical composition and potential effects on human health are lacking. A methanol hazelnut shells extract was prepared and dried. Our investigation allowed the isolation and characterization of different classes of phenolic compounds, including neolignans, and a diarylheptanoid, which contribute to a high total polyphenol content (193.8 ± 3.6 mg of gallic acid equivalents (GAE/g of extract. Neolignans, lawsonicin and cedrusin, a cyclic diarylheptanoid, carpinontriol B, and two phenol derivatives, C-veratroylglycol, and β-hydroxypropiovanillone, were the main components of the extract (0.71%–2.93%, w/w. The biological assays suggested that the extract could be useful as a functional ingredient in food technology and pharmaceutical industry showing an in vitro scavenging activity against the radical 1,1-diphenyl-2-picrylhydrazyl radical (DPPH (EC50 = 31.7 μg/mL with respect to α-tocopherol EC50 = 10.1 μg/mL, and an inhibitory effect on the growth of human cancer cell lines A375, SK-Mel-28 and HeLa (IC50 = 584, 459, and 526 μg/mL, respectively. The expression of cleaved forms of caspase-3 and poly(ADP-ribose polymerase-1 (PARP-1 suggested that the extract induced apoptosis through caspase-3 activation in both human malignant melanoma (SK-Mel-28 and human cervical cancer (HeLa cell lines. The cytotoxic activity relies on the presence of the neolignans (balanophonin, and phenol derivatives (gallic acid, showing a pro-apoptotic effect on the tested cell lines, and the neolignan, cedrusin, with a cytotoxic effect on A375 and HeLa cells.

  4. Apoptotic induction activity of Dactyloctenium aegyptium (L. P.B. and Eleusine indica (L. Gaerth. extracts on human lung and cervical cancer cell lines

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    Pintusorn Hansakul

    2009-08-01

    Full Text Available Dactyloctenium aegyptium (L. P.B. (Yaa paak khwaai and Eleusine indica (L. Gaerth. (Yaa teen-ka have long been used in traditional Thai medicine because of their diuretic, anti-inflamatory, and antipyretic effects. The present study examined the antiproliferative and cytotoxic effects of the hexane and butanolic extracts of these two grass species. All the grass extracts exhibited selective growth inhibition effect on human lung cancer (A549 and cervical cancer (HeLa cells relative to normal human lung MRC-5 fibroblasts with IC50 values in a range of 202 to 845 mg/ml. Apparently, HeLa cellswere more sensitive to the extracts than A549 cells. Moreover, all the extracts induced lethality in both cancer cell lines atconcentrations close to 1,000 mg/ml, indicating their selective cytotoxicity effects. ELISA assay showed that only the hexaneextract of D. aegyptium (L. P.B. and E. indica (L. Gaerth. significantly increased the apoptotic level in extract-treatedA549 cells. However, DNA ladder assay detected classic DNA ladder patterns, a characteristic feature of apoptosis, in both cancer cell lines treated with all the extracts in a dose- and time-dependent manner. Taken together, these results indicatethat the cytotoxic activity of the grass extracts against lung and cervical cancer cells is mediated through the induction ofapoptosis.

  5. The Shaggy Ink Cap Medicinal Mushroom, Coprinus comatus (Higher Basidiomycetes) Extract Induces Apoptosis in Ovarian Cancer Cells via Extrinsic and Intrinsic Apoptotic Pathways.

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    Rouhana-Toubi, Amal; Wasser, Solomon P; Fares, Fuad

    2015-01-01

    In a previous study, ethyl acetate extract of Coprinus comatus was found to reduce viability of human ovarian cancer cells. The objective of the current research was to clarify the mechanism of action of this extract. Ovarian cancer cells (ES-2) were subjected to ethyl acetate extract of C. comatus for different concentrations or exposure times. Cell cycle analysis and annexin V staining were performed using an automated flow cytometer. DNA fragmentation was detected using the TUNEL assay. Western blot analysis was performed for the assessment of activation of caspases -3, -8, and -9. Results revealed that treatment of ES-2 cells with ethyl acetate extract of C. comatus (100 μg/ml medium), for 48 h or for 72 h resulted in an increased number of cells at the sub-G1 phase of the cell cycle. These treatments also resulted in an increased number of apoptotic cells (positively stained by annexin and positively labeled by TUNEL), in comparison to the control. Reduced levels of procaspases -3, -8, and-9 were also detected in treated cells. In conclusion, ethyl acetate extract of C. comatus induces apoptosis in ovarian cancer cells (ES-2), via both extrinsic and intrinsic pathways. Meanwhile, more investigations are needed to demonstrate weather the apoptotic effect on ovarian cancer cells is accomplished by one active compound, or combined activities of different compounds that exist in the extract.

  6. Sarsaparilla (Smilax Glabra Rhizome extract inhibits migration and invasion of cancer cells by suppressing TGF-β1 pathway.

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    Tiantian She

    Full Text Available Sarsaparilla, also known as Smilax Glabra Rhizome (SGR, was shown to modulate immunity, protect against liver injury, lower blood glucose and suppress cancer. However, its effects on cancer cell adhesion, migration and invasion were unclear. In the present study, we found that the supernatant of water-soluble extract from SGR (SW could promote adhesion, inhibit migration and invasion of HepG2, MDA-MB-231 and T24 cells in vitro, as well as suppress metastasis of MDA-MB-231 cells in vivo. Results of F-actin and vinculin dual staining showed the enhanced focal adhesion in SW-treated cells. Microarray analysis indicated a repression of TGF-β1 signaling by SW treatment, which was verified by real-time RT-PCR of TGF-β1-related genes and immunoblotting of TGFBR1 protein. SW was also shown to antagonize TGF-β1-promoted cell migration. Collectively, our study revealed a new antitumor function of Sarsaparilla in counteracting invasiveness of a subset of cancer cells by inhibiting TGF-β1 signaling.

  7. Effects of Urtica dioica dichloromethane extract on cell apoptosis and related gene expression in human breast cancer cell line (MDA-MB-468).

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    Mohammadi, A; Mansoori, B; Goldar, S; Shanehbandi, D; Khaze, V; Mohammadnejad, L; Baghbani, E; Baradaran, B

    2016-02-29

    Breast cancer is the most common cancer among women in worldwide, especially in developing countries. Therefore, a large number of anticancer agents with herbal origins have been reported against this deadly disease. This study is the first to examine the cytotoxic and apoptotic effects of Urtica dioica in MDA-MB-468, human breast adenocarcinoma cells. The 3-(4,5-dimethylethiazol-2 yl)-2,5- diphenyltetrazolium (MTT) reduction and trypan-blue exclusion assay were performed in MDA-MB-468 cells as well as control cell line L929 to analyze the cytotoxic activity of the dichloromethane extract. In addition, Apoptosis induction of Urtica dioica on the MDA-MB-468 cells was assessed using TUNEL (terminal deoxy transferase (TdT)-mediated dUTP nick- end labeling) assay and DNA fragmentation analysis and real-time polymerase chain reaction (PCR). The results showed that the extract significantly inhibited cell growth and viability without inducing damage to normal control cells. Nuclei Staining in TUNEL and DNA fragments in DNA fragmentation assay and increase in the mRNA expression levels of caspase-3, caspase-9, decrease in the bcl2 and no significant change in the caspase-8 mRNA expression level, showed that the induction of apoptosis was the main mechanism of cell death that induce by Urtica dioica extract. Our results suggest that urtica dioica dichloromethane extract may contain potential bioactive compound(s) for the treatment of breast adenocarcinoma.

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

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    Zhongyuan Zhang

    2013-01-01

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

  9. Promising cytotoxic activity profile of fermented wheat germ extract (Avemar® in human cancer cell lines

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    Voigt Wieland

    2011-04-01

    Full Text Available Abstract Fermented wheat germ extract (FWGE is currently used as nutrition supplement for cancer patients. Limited recent data suggest antiproliferative, antimetastatic and immunological effects which were at least in part exerted by two quinones, 2-methoxy benzoquinone and 2,6-dimethoxybenzquinone as ingredients of FWGE. These activity data prompted us to further evaluate the in vitro antiproliferative activity of FWGE alone or in combination with the commonly used cytotoxic drugs 5-FU, oxaliplatin or irinotecan in a broad spectrum of human tumor cell lines. We used the sulforhodamine B assay to determine dose response relationships and IC50-values were calculated using the Hill equation. Drug interaction of simultaneous and sequential drug exposure was estimated using the model of Drewinko and potential clinical activity was assessed by the model of relative antitumor activity (RAA. Apoptosis was detected by DNA gel electrophoresis. FWGE induced apoptosis and exerted significant antitumor activity in a broad spectrum of 32 human cancer cell lines. The highest activity was found in neuroblastoma cell lines with an average IC50 of 0.042 mg/ml. Furthermore, IC50-range was very narrow ranging from 0.3 mg/ml to 0.54 mg/ml in 8 colon cancer cell lines. At combination experiments in colon cancer cell lines when FWGE was simultaneously applied with either 5-FU, oxaliplatin or irinotecan we observed additive to synergistic drug interaction, particularly for 5-FU. At sequential drug exposure with 5-FU and FWGE the observed synergism was abolished. Taken together, FWGE exerts significant antitumor activity in our tumor model. Simultaneous drug exposure with FWGE and 5-FU, oxaliplatin or irinotecan yielded in additive to synergistic drug interaction. However, sequential drug exposure of 5-FU and FWGE in colon cancer cell lines appeared to be schedule-dependent (5-FU may precede FWGE. Further evaluation of FWGE as a candidate for clinical combination drug

  10. Aged black garlic extract inhibits HT29 colon cancer cell growth via the PI3K/Akt signaling pathway.

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    Dong, Menghua; Yang, Guiqing; Liu, Hanchen; Liu, Xiaoxu; Lin, Sixiang; Sun, Dongning; Wang, Yishan

    2014-03-01

    Accumulating evidence indicates that aged black garlic extract (ABGE) may prove beneficial in preventing or inhibiting oncogenesis; however, the underlying mechanisms have not been fully elucidated. The present study aimed to investigate the effects of ABGE on the proliferation and apoptosis of HT29 colon cancer cells. Our results demonstrated that ABGE inhibited HT29 cell growth via the induction of apoptosis and cell cycle arrest. We further investigated the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signal transduction pathway and the molecular mechanisms underlying the ABGE-induced inhibition of HT29 cell proliferation. We observed that ABGE may regulate the function of the PI3K/Akt pathway through upregulating PTEN and downregulating Akt and p-Akt expression, as well as suppressing its downstream target, 70-kDa ribosomal protein S6 kinase 1, at the mRNA and protein levels. In conclusion, these findings suggest that the PI3K/Akt signal transduction pathway is crucial for the development of colon cancer. ABGE inhibited the growth and induced apoptosis in HT29 cells through the inhibition of the PI3K/Akt pathway, suggesting that ABGE may be effective in the prevention and treatment of colon cancer in humans.

  11. Chemopreventive and immunomodulatory effects of Murraya koenigii aqueous extract on 4T1 breast cancer cell-challenged mice.

    Science.gov (United States)

    Yeap, Swee Keong; Abu, Nadiah; Mohamad, Nurul Elyani; Beh, Boon Kee; Ho, Wan Yong; Ebrahimi, Siamak; Yusof, Hamidah Mohd; Ky, Huynh; Tan, Sheau Wei; Alitheen, Noorjahan Banu

    2015-09-04

    The progression of breast cancer is increasing at an alarming rate, particularly in western countries. Meanwhile, the lower incidence in Asian countries could be attributed to the heavy incorporation of green leaves vegetables or spices in their diets. Murraya koenigii (MK) or often times known as curry leaves are common spice used mostly in tropical countries. Anti-inflammatory and chemopreventive effects of MK aqueous extract on 4T1 breast cancer cell-challenged mice were evaluated. Herein, cytotoxic activity of MK was first tested on 4T1 cells in vitroby MTT assay. Then, in vivo chemopreventive study was conducted where mice were fed with extracts prior to and after inducing the tumor (inoculation). Tumor size was monitored post-4T1 inoculation. At the end of experiment, histopathology of tumor sections, T cell immunophenotyping, tumor nitric oxide level, serum cytokine level and qPCR analysis on expression of iNOS, iCAM, NF-kB and c-MYC were performed. MK reduced the tumors' size and lung metastasis aside from inhibited the viability of 4T1 cells in vitro. Furthermore, it decreased the level of nitric oxide and inflammation-related cytokines and genes, including iNOS, iCAM, NF-kB and c-MYC. The results propose that, MK managed to inhibit the progression of tumor via immunostimulatory effect and inflammatory reaction within the tumor samples. This suggests that MKconsumption could be a savior in the search of new chemopreventive agents.

  12. Induction of apoptosis and oxidative stress in estrogen receptor-negative breast cancer, MDA-MB231 cells, by ethanolic mango seed extract.

    Science.gov (United States)

    Abdullah, Al-Shwyeh Hussah; Mohammed, Abdulkarim Sabo; Rasedee, Abdullah; Mirghani, Mohamed Elwathig Saeed; Al-Qubaisi, Mothanna Sadiq

    2015-03-09

    In this study, the effect of mango kernel extract in the induction of apoptosis of the breast cancer (MDA-MB-231) cell line was examined. This is an attempt to discover alternatives to current therapeutic regimes in the treatment of breast cancers. The pro-apoptotic markers, Bax, cytochrome c, caspases-. -8 and -9, and anti-apoptotic markers, Bcl-2, p53 and glutathione were determined in MDA-MB231 cells treated for 12 and 24 h with mango kernel extract. The results showed that the extract produced a time- and dose-dependent increases in pro-apoptotic proteins and oxidative stress markers with a corresponding decrease in anti-apoptotic markers. Based on the findings, mango kernel extract modulates redox balance in MDA-MB-231 breast cancer cells with a tendency for apoptotic cell death. The changes observed in this study may collectively underlie the basis for the cell death induced in MDA-MB-231 breast cancer cells by mango kernel extract. Thus, mango kernel extract has potential to be developed into an antibreast cancer mixture, and hence these results are worth studying further.

  13. Automated Information Extraction on Treatment and Prognosis for Non-Small Cell Lung Cancer Radiotherapy Patients: Clinical Study.

    Science.gov (United States)

    Zheng, Shuai; Jabbour, Salma K; O'Reilly, Shannon E; Lu, James J; Dong, Lihua; Ding, Lijuan; Xiao, Ying; Yue, Ning; Wang, Fusheng; Zou, Wei

    2018-02-01

    In outcome studies of oncology patients undergoing radiation, researchers extract valuable information from medical records generated before, during, and after radiotherapy visits, such as survival data, toxicities, and complications. Clinical studies rely heavily on these data to correlate the treatment regimen with the prognosis to develop evidence-based radiation therapy paradigms. These data are available mainly in forms of narrative texts or table formats with heterogeneous vocabularies. Manual extraction of the related information from these data can be time consuming and labor intensive, which is not ideal for large studies. The objective of this study was to adapt the interactive information extraction platform Information and Data Extraction using Adaptive Learning (IDEAL-X) to extract treatment and prognosis data for patients with locally advanced or inoperable non-small cell lung cancer (NSCLC). We transformed patient treatment and prognosis documents into normalized structured forms using the IDEAL-X system for easy data navigation. The adaptive learning and user-customized controlled toxicity vocabularies were applied to extract categorized treatment and prognosis data, so as to generate structured output. In total, we extracted data from 261 treatment and prognosis documents relating to 50 patients, with overall precision and recall more than 93% and 83%, respectively. For toxicity information extractions, which are important to study patient posttreatment side effects and quality of life, the precision and recall achieved 95.7% and 94.5% respectively. The IDEAL-X system is capable of extracting study data regarding NSCLC chemoradiation patients with significant accuracy and effectiveness, and therefore can be used in large-scale radiotherapy clinical data studies.

  14. Oxidative Stress-Mediated Apoptosis Induced by Ethanolic Mango Seed Extract in Cultured Estrogen Receptor Positive Breast Cancer MCF-7 Cells

    OpenAIRE

    Al-Shwyeh Hussah Abdullah; Abdulkarim Sabo Mohammed; Abdullah Rasedee; Mohamed Elwathig Saeed Mirghani

    2015-01-01

    Breast cancer has become a global health issue requiring huge expenditures for care and treatment of patients. There is a need to discover newer cost-effective alternatives for current therapeutic regimes. Mango kernel is a waste product with potential as a source of anti-cancer phytochemicals, especially since it is non-toxic towards normal breast cell lines at concentrations for which it induces cell death in breast cancer cells. In this study, the anti-cancer effect of mango kernel extract...

  15. Anti-proliferation and Apoptosis Induction of Aqueous Leaf Extract of Carica papaya L. on Human Breast Cancer Cells MCF-7.

    Science.gov (United States)

    Zuhrotun Nisa, Fatma; Astuti, Mary; Murdiati, Agnes; Mubarika Haryana, Sofia

    2017-01-01

    Breast cancer is the most frequently diagnosed cancer in women. Chemotherapy is the main method of breast cancer treatment but there are side effects. Carica papaya leaves is vegetable foods consumed by most people of Indonesia have potential as anticancer. The aim of this study was to investigate anti-proliferative and apoptotic induced effect of aqueous papaya leaves extracts on human breast cancer cell lines MCF-7. Inhibitory on cell proliferation was measured by MTT assay while apoptosis induction was measured using Annexin V. The results showed that papaya leaf can inhibit the proliferation of human breast cancer cells MCF-7 with IC50 in 1319.25 μg mL-1. The IC50 values of papaya leaf extract was higher than the IC50 value quercetin and doxorubicin. Papaya leaf extract can also induce apoptosis of breast cancer cells MCF-7 about 22.54% for concentration 659.63 μg mL-1 and about 20.73% for concentration 329.81 μg mL-1. The percentage of cell apoptosis of papaya leaf extract lower than doxorubicin but higher than quercetin. This study indicated that papaya leaf extract have potential as anticancer through mechanism anti-proliferation and apoptosis induction.

  16. Therapeutic Effect of Supercritical CO2 Extracts of Curcuma Species with Cancer Drugs in Rhabdomyosarcoma Cell Lines.

    Science.gov (United States)

    Ramachandran, Cheppail; Quirin, Karl-W; Escalon, Enrique A; Lollett, Ivonne V; Melnick, Steven J

    2015-08-01

    Synergistic effect of supercritical CO2 extracts of Curcuma species with conventional chemotherapeutic drugs was investigated in human alveolar (SJRH30) and embryonal (RD) rhabdomyosarcoma cell lines. The Curcuma amada (mango ginger) (CA) extract showed the highest levels of cytotoxicity with inhibitory concentration IC50 values of 7.133 µg/ml and 7.501 µg/ml for SJRH30 and RD cell lines, respectively, as compared with Curcuma longa (turmeric) and Curcuma xanthorrhiza (Javanese turmeric) extracts. CA showed synergistic cytotoxic effects with vinblastine (VBL) and cyclophosphamide (CP) as indicated by the combination index values of <1 for VBL + CA, CP + CA, and VBL + CP + CA combinations in both embryonal and alveolar rhabdomyosarcomas. When lower doses of CA (0.1-0.2 µg/ml) were combined with cancer drugs like CP and VBL, caspase-3 activity increased significantly compared with individual agents and correlated with the percentage of apoptotic cells. CA in combination with VBL and CP induced a higher percentage of apoptosis than single agents in both cell lines. CA also modulated the expression of genes associated with intrinsic pathway of apoptosis (Bcl-2, Bax, Bak, and p53) and also inhibited the expression of genes associated with inflammation such as COX-2 and NF-κB. Xenograft studies with SJRH30 tumors in nude mice showed that CA treatment inhibited tumor growth rate with and without VBL and increased the survival rate significantly. These results suggest that CA can be evaluated further as an adjuvant with cancer drugs for the treatment of rhabdomyosarcoma patients. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  17. Polyphenol stabilized colloidal gold nanoparticles from Abutilon indicum leaf extract induce apoptosis in HT-29 colon cancer cells.

    Science.gov (United States)

    Mata, Rani; Nakkala, Jayachandra Reddy; Sadras, Sudha Rani

    2016-07-01

    Green synthesized gold nanoparticles have received substantial attention owing to their biomedical applications, particularly in cancer therapy. Although anticancer activities of green synthesized gold nanoparticles have been reported earlier, the underlying mechanism behind their anticancer activity is still to be understood. The present study, describes the green synthesis of Abutilon indicum gold nanoparticles (AIGNPs) from Abutilon indicum leaf extract (AILE) and their cytotoxic mechanism in colon cancer cells. Dimensions of spherical shaped AIGNPs were found to be in the range of 1-20nm as determined by TEM. GC-MS and FTIR analysis indicated the presence of polyphenolic groups in AILE, which might have been involved in the stabilization of AIGNPs. In vitro free radical scavenging analysis revealed the radical quenching activity of AIGNPs. Further, the AIGNPs exhibited cytotoxicity in HT-29 colon cancer cells with IC50 values of 210 and 180μg/mL after 24 and 48h. This was mediated through nuclear morphological changes and cell membrane damage as evidenced by acridine orange/ethidium bromide, propidium iodide and AnnexinV-Cy3 staining methods. Mechanism of the observed cytotoxicity of AIGNPs was explained on the basis of increased levels of reactive oxygen species and simultaneous reduction in cellular antioxidants, which might have caused mitochondrial membrane potential loss, DNA damage and G1/S phase cell cycle arrest. Expression of cleaved Caspase-9, Caspase-8, Caspase-3, Lamin A/C and PARP, provided the clues for the induction of intrinsic and extrinsic apoptosis pathways in AIGNPs treated HT-29 cells. The study provides a preliminary guidance towards the development of colon cancer therapy using green synthesized gold nanoparticles. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Viscum Album Var Hot Water Extract Mediates Anti-cancer Effects through G1 Phase Cell Cycle Arrest in SK-Hep1 Human Hepatocarcinoma cells.

    Science.gov (United States)

    dela Cruz, Joseph Flores; Kim, Yeon Soo; Lumbera, Wenchie Marie Lara; Hwang, Seong Gu

    2015-01-01

    Viscum album var (VAV) also known as mistletoe, has long been categorized as a traditional herbal medicine in Asia. In addition to its immunomodulating activities, mistletoe has also been used in the treatment of chronic hepatic disorders in China and Korea. There are numerous reports showing that VAV possesses anti-cancer effects, however influence on human hepatocarcinoma has never been elucidated. In the present study, hot water extracts of VAV was evaluated for its potential anti-cancer effect in vitro. SK-Hep1 cells were treated with VAV (50-400 ug/ml) for both 24 and 48 hours then cell viability was measured by cell counting kit-8 (CCK-8). Flow cytometry analysis was used to measure the proportion of SK-Hep1 in the different stages of cell cycle. RT-PCR and Western blot analysis were conducted to measure expression of cell cycle arrest related genes and proteins respectively. VAV dose dependently inhibited the proliferation of SK-Hep1 cells without any cytotoxicity with normal Chang liver cell (CCL-13). Flow cytometry analysis showed that VAV extract inhibited the cell cycle of SK-Hep1 cells via G1 phase arrest. RT-PCR and Western blot analysis both revealed that cyclin dependent kinase 2 (Cdk2) and cyclin D1 gene expression were significantly down regulated while p21 was upregulated dose dependently by VAV treatment. Combined down regulation of Cdk2, Cyclin D1 and up regulation of p21 can result in cell death. These results indicate that VAV showed evidence of anti-cancer activity through G1 phase cell cycle arrest in SK-Hep1 cells.

  19. Transcriptome Profiling of Caco-2 Cancer Cell Line following Treatment with Extracts from Iodine-Biofortified Lettuce (Lactuca sativa L..

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    Aneta A Koronowicz

    Full Text Available Although iodization of salt is the most common method used to obtain iodine-enriched food, iodine deficiency disorders are still a global health problem and profoundly affect the quality of human life. Iodine is required for the synthesis of thyroid hormones, which are crucial regulators of human metabolism, cell growth, proliferation, apoptosis and have been reported to be involved in carcinogenesis. In this study, for the first time, we evaluated the effect of iodine-biofortified lettuce on transcriptomic profile of Caco-2 cancer cell line by applying the Whole Human Genome Microarray assay. We showed 1326 differentially expressed Caco-2 transcripts after treatment with iodine-biofortified (BFL and non-fortified (NFL lettuce extracts. We analysed pathways, molecular functions, biological processes and protein classes based on comparison between BFL and NFL specific genes. Iodine, which was expected to act as a free ion (KI-NFL or at least in part to be incorporated into lettuce macromolecules (BFL, differently regulated pathways of numerous transcription factors leading to different cellular effects. In this study we showed the inhibition of Caco-2 cells proliferation after treatment with BFL, but not potassium iodide (KI, and BFL-mediated induction of mitochondrial apoptosis and/or cell differentiation. Our results showed that iodine-biofortified plants can be effectively used by cells as an alternative source of this trace element. Moreover, the observed differences in action of both iodine sources may suggest a potential of BFL in cancer treatment.

  20. The effect of ethanol extract of mangostene (Garcinia Mangostana Linn. peel on tongue cancer cells Supri's Clone-1 apoptosis, in vitro

    Directory of Open Access Journals (Sweden)

    Maria Aurora Titiana

    2011-11-01

    Full Text Available Apoptosis or programmed cell death serves to regulate physiological and pathological conditions. Garcinia mangostana Linn. is one of the medical herbs that is widely used to suppress human tongue cancer growth by inducing apoptosis. The research aimed to analyze the effect of ethanol extract of Garcinia mangostana Linn. on tongue cancer cells apoptosis Supri's Clone-1 (SP-C1. The type of the research was an experimental laboratory. Tongue cancer cells SP-C1 were treated by various ethanol extract concentrations (0, 300, 400, 500, 600, 700 pg/ml of Garcinia mangostana Linn. to detect the apoptosis, which was done by acridine orange and ethidium bromide coloring tests. The number of tongue cancer cells SP-C1 2x104 cells/dish. Observation on cells apoptosis was observed by a fluorescent microscope with 40 x magnification. The data were analyzed using one-way ANOVA and was followed by Post Hoc test (Tukey-test with 95% significance level. The result showed that tongue cancer cells SP-C1 apoptosis treated by various ethanol extracts of Garcinia mangostana Linn. increase significantly. The highest effect of apoptosis was detected at the 700 pg/ml concentration that has an effect on the percentage of tongue cancer cells apoptosis by 65%.

  1. Crocus sativus L. (saffron) stigma aqueous extract induces apoptosis in alveolar human lung cancer cells through caspase-dependent pathways activation.

    Science.gov (United States)

    Samarghandian, Saeed; Borji, Abasalt; Farahmand, Seyed Kazem; Afshari, Reza; Davoodi, Saeideh

    2013-01-01

    Worldwide, lung cancer is the most common form of cancer. Saffron has been used in folk medicine for centuries. We investigated the potential of saffron to induce cytotoxic and apoptotic effects in lung cancer cells (A549). We also examined the caspase-dependent pathways activation of saffron-induced apoptosis against the A549 cells. A549 cells were incubated with different concentrations of saffron extract; then cell morphological changes, cell viability, and apoptosis were determined by the normal invertmicroscope, MTT assay, Annexin V and propidium iodide, and flow cytometric analysis, respectively. Activated caspases were detected by treatment of saffron in lung cancer cells using fluorescein-labeled inhibitors of polycaspases. The proliferation of the A549 cells were decreased after treatment with saffron in a dose- and time-dependent manner. The percentage of apoptotic cells increased with saffron concentrations. Saffron induced morphological changes, decreased percentage of viable cells, and induced apoptosis. Saffron could induce apoptosis in the A549 cells and activate caspase pathways. The levels of caspases involved in saffron-induced apoptosis in the A549 cells indicating caspase-dependent pathway were induced by saffron. The anticancer activity of the aqueous extract of saffron could be attributed partly to its inhibition of the cell proliferation and induction of apoptosis in cancer cells through caspase-dependent pathways activation.

  2. Crocus sativus L. (Saffron Stigma Aqueous Extract Induces Apoptosis in Alveolar Human Lung Cancer Cells through Caspase-Dependent Pathways Activation

    Directory of Open Access Journals (Sweden)

    Saeed Samarghandian

    2013-01-01

    Full Text Available Worldwide, lung cancer is the most common form of cancer. Saffron has been used in folk medicine for centuries. We investigated the potential of saffron to induce cytotoxic and apoptotic effects in lung cancer cells (A549. We also examined the caspase-dependent pathways activation of saffron-induced apoptosis against the A549 cells. A549 cells were incubated with different concentrations of saffron extract; then cell morphological changes, cell viability, and apoptosis were determined by the normal invertmicroscope, MTT assay, Annexin V and propidium iodide, and flow cytometric analysis, respectively. Activated caspases were detected by treatment of saffron in lung cancer cells using fluorescein-labeled inhibitors of polycaspases. The proliferation of the A549 cells were decreased after treatment with saffron in a dose- and time-dependent manner. The percentage of apoptotic cells increased with saffron concentrations. Saffron induced morphological changes, decreased percentage of viable cells, and induced apoptosis. Saffron could induce apoptosis in the A549 cells and activate caspase pathways. The levels of caspases involved in saffron-induced apoptosis in the A549 cells indicating caspase-dependent pathway were induced by saffron. The anticancer activity of the aqueous extract of saffron could be attributed partly to its inhibition of the cell proliferation and induction of apoptosis in cancer cells through caspase-dependent pathways activation.

  3. Inhibitory effects of crude extracts from some edible Thai plants against replication of hepatitis B virus and human liver cancer cells

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    Waiyaput Wanwisa

    2012-12-01

    Full Text Available Abstract Background Edible plants such as Cratoxylum formosum (Jack Dyer, Curcumin longa Lin, Momordica charantia Lin and Moringa oleifera Lam have long been believed in Thai culture to relieve ulcers and the symptoms of liver disease. However, little is known about their anti-liver cancer properties and antiviral activity against hepatitis B virus (HBV. The aim of this study was to investigate the anti-liver cancer and anti-HBV activities of crude extracts from these edible plants on human liver cancer cells. Methods Plant samples were prepared and extracted using buffer and hydro-alcoholic solvents. The MTT assay was performed to investigate the effects of the plant extracts on the cell viability of HepG2 cells. The inhibitory effect on replication of HBV was analysed by determining the level of HBV covalently closed circular DNA (cccDNA in transiently transfected HepG2 cells with the DNA expression plasmid of the HBV genome using a quantitative real-time PCR. Results Buffer and hydroalcoholic extracts from C. formosum (leaf reduced cell viability of HepG2 cells and they also inhibited HBV cccDNA. Crude extracts from C. longa (bulb in both solvents did not have any cytotoxic effects on the HepG2 cells, but they significantly decreased the level of HBV cccDNA. Buffer extracts from the leaves of M. charantia and the fruits of M. oleifera showed to have anti-HBV activity and also a mild cytotoxicity effect on the HepG2 cells. In addition, leaves of M. Oleifera extracted by hydroalcoholic solvent drastically decreased the level of cccDNA in transiently transfected HepG2 cells. Conclusion Some crude extracts of edible plants contain compounds that demonstrate anti-liver cancer and anti-HBV activities.

  4. Changes in free amino acid, protein, and flavonoid content in jujube (Ziziphus jujube) fruit during eight stages of growth and antioxidative and cancer cell inhibitory effects by extracts.

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    Choi, Suk-Hyun; Ahn, Jun-Bae; Kim, Hyun-Jeong; Im, Nam-Kyung; Kozukue, Nobuyuki; Levin, Carol E; Friedman, Mendel

    2012-10-17

    Jujube (Ziziphus jujube) was analyzed at eight stages of ripeness (S1-8) for protein, by HPLC and mass spectroscopy for free amino acids and flavonoids, and by colorimetry for total flavonoids and antioxidative activity. The ripe fruit had lower levels of protein, flavonoids, and antioxidative activity than that of the unripe fruit. Free amino acids levels peaked at S5, due mainly to an increase in free asparagine. Extracts were also tested against four cell lines using the MTT cell viability assay. All growth stages dose-dependently inhibited HeLa cervical cancer cells, whereas the inhibition of Hel299 normal lung and A549 lung cancer cells decreased as the fruit matured and was well correlated with the flavonoid content and antioxidative activity. Chang normal liver cells were inhibited by only the S5 extract. U937 lymphoma cells were unaffected by the extracts. These results show the effect of fruit maturity on nutritional and health-promoting components.

  5. Grape seed extract dose-responsively decreases disease severity in a rat model of mucositis; concomitantly enhancing chemotherapeutic effectiveness in colon cancer cells.

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    Cheah, Ker Yeaw; Howarth, Gordon Stanley; Bastian, Susan Elaine Putnam

    2014-01-01

    Mucositis is a serious disorder of the gastrointestinal tract that results from cancer chemotherapy. We investigated the effects of increasing grape seed extract doses on the severity of chemotherapy in a rat model and its coincident impact on chemotherapeutic effectiveness in colon cancer cells. Female Dark Agouti rats were gavaged with grape seed extract (400-1000 mg/kg) or water (day 3-11) and were injected intraperitoneally with 5-Fluorouracil (150 mg/kg) or saline (control) on day 9 to induce mucositis. Daily metabolic data were collected and rats were sacrificed on day 12. Intestinal tissues were collected for histological and myeloperoxidase analyses. Caco-2 cell viability was examined in response to grape seed extract in combination with 5-Fluorouracil by 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide) assay. Compared with 5-Fluorouracil controls, grape seed extract (400-1000 mg/kg) significantly decreased the histological damage score (PGrape seed extract (1000 mg/kg) increased jejunal crypt depth by 25% (PGrape seed extract (600 mg/kg) decreased myeloperoxidase activity by 55% (PGrape seed extract was more effective at ameliorating 5-Fluorouracil induced intestinal injury, with effects most pronounced in the proximal jejunum. Grape seed extract (10-25 ug/mL) significantly enhanced the growth-inhibitory effects of 5-Fluorouracil by 26% (PGrape seed extract may represent a new therapeutic option to decrease the symptoms of intestinal mucositis while concurrently impacting on the viability of colon cancer cells.

  6. Effects of Ethyl Acetate Extracts from the Polycephalomyces nipponicus Isolate Cod-MK1201 (Ascomycetes) against Human Pathogenic Bacteria and a Breast Cancer Cell Line.

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    Sangdee, Kusavadee; Seephonkai, Prapairat; Buranrat, Benjaporn; Surapong, Nilawan; Sangdee, Aphidech

    2016-01-01

    This study aimed to identify a suitable organic solvent for extracting bioactive compounds from Polycephalomyces nipponicus and to evaluate the antibacterial and anticancer activities of the extracts obtained. Only extracts obtained with ethyl acetate exhibited antibacterial activity, so ethyl acetate was chosen for large-scale extraction. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Gram-positive and Gram-negative human pathogenic bacteria of the 3 ethyl acetate-derived extracts-ethyl acetate extract from P. nipponicus (PN-ME), ethyl acetate extract after defatting (PN-ME*), and ethyl acetate extract after refluxation (PN-ME')-were determined. PN-ME' exhibited the most potent activity, inhibiting 12 of the 18 test bacteria, especially Bacillus cereus ATCC 11778 and Vibrio cholera (O1) DMST 9700, with low MIC and MBC values. PN-ME* showed greater inhibitory activity than PN-ME. The effects of the extracts on bacterial cell morphology were also determined. After 120 minutes of treatment with PN-ME* or PN-ME', B. cereus ATCC 11778 exhibited an abnormal rod-shaped cell structure, with some cells elongated to multiple times their original size and others appearing collapsed. V cholera (O1) DMST 9700 cells showed shrinkage and the formed subsurface cavities. PN-ME* and PN-ME' also inhibited the growth of MCF-7 breast cancer cells. In conclusion, the fungal isolate P. nipponicus Cod-MK1201 represents a source of antibacterial and anti-breast cancer compounds.

  7. Cytotoxic Activity of Kenaf Seed Oils from Supercritical Carbon Dioxide Fluid Extraction towards Human Colorectal Cancer (HT29 Cell Lines

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    Siti Aisyah Abd Ghafar

    2013-01-01

    Full Text Available Kenaf (Hibiscus cannabinus from the family Malvaceae, is a valuable fiber plant native to India and Africa and is currently planted as the fourth commercial crop in Malaysia. Kenaf seed oil contains alpha-linolenic acid, phytosterol such as β-sitosterol, vitamin E, and other antioxidants with chemopreventive properties. Kenaf seeds oil (KSO was from supercritical carbon dioxide extraction fluid (SFE at 9 different permutations of parameters based on range of pressures from 200 to 600 bars and temperature from 40 to 80°C. They were 200/40, 200/60, 200/80, 400/40, 400/60, 400/80, 600/40, 600/60, and 600/80. Extraction from 9 parameters of KSO-SFE was screened for cytotoxicity towards human colorectal cancer cell lines (HT29 and mouse embryonic fibroblast (NIH/3T3 cell lines using MTS assay. KSO-SFE at 600/40 showed the strongest cytotoxicity towards HT29 with IC50 of 200 µg/mL. The IC50 for NIH/3T3 was not detected even at highest concentration employed. Cell cycle analysis showed a significant increase in the accumulation of KSO-SFE-treated cells at sub-G1 phase, indicating the induction of apoptosis by KSO-SFE. Further apoptosis induction was confirmed by Annexin V/PI and AO/PI staining.

  8. The Value of Caspase-3 after the Application ofAnnona muricataLeaf Extract in COLO-205 Colorectal Cancer Cell Line.

    Science.gov (United States)

    Abdullah, Murdani; Syam, Ari Fahrial; Meilany, Sofy; Laksono, Bayu; Prabu, Oryza Gryagus; Bekti, Heri Setiyo; Indrawati, Lili; Makmun, Dadang

    2017-01-01

    Annona muricata , commonly known as soursop, contains annonacin, acetogenin, and polyphenol which are known to have chemopreventive effects on cancer. In this study, we tend to evaluate the apoptosis-inducing effect of soursop ( Annona muricata ) leaf extract on the colorectal cancer cell line COLO-205 through the activities of caspase-3 which is a marker of cell apoptosis. Cell cultures were incubated with soursop leaf with a concentration of 10  μ g/ml and then compared with those of the incubated positive control leucovorin 10  μ g/ml and placebo as a negative control. The apoptotic activity of caspase-3 was measured with ELISA. After the administration of each treatment in the colorectal cancer cell line COLO-205, the expression of caspase-3 activity was 1422 ng/ml after incubation with the extract of Annona muricata leaves, 1373 ng/ml after the administration of leucovorin, and 1297 ng/ml in the one with placebo. Annona muricata leaf extract elevated caspase-3 by 1.09 times compared to that of the pure cell line. Annona muricata leaf extract had a higher value of caspase-3 activity than leucovorin and placebo in the COLO-205 colorectal cancer cell line. These results may suggest that Annona muricata leaf extract had anticancer properties by enhancing caspase-3 activity which is a proapoptotic marker.

  9. Maytenus ilicifolia dry extract protects normal cells, induces apoptosis and regulates Bcl-2 in human cancer cells.

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    Araújo Júnior, Raimundo Fernandes de; Oliveira, Ana Luiza Cabral de Sá Leitão; Pessoa, Jonas Bispo; Garcia, Vinícios Barreto; Guerra, Gerlane Coelho Bernardo; Soares, Luiz Alberto Lira; Souza, Tatiane Pereira de; Petrovick, Pedro Ros; Araújo, Aurigena Antunes de

    2013-11-01

    Maytenus is the largest genus of the family Celastraceae and the species Maytenus ilicifolia (popularly known as 'Espinheira Santa'). It is widely used in traditional Brazilian medicine to treat stomach conditions including nausea, gastritis, and ulcers. In this study, the apoptotic effects of a spray-dried extract of M. ilicifolia (SDEMI) was evaluated using human hepatocellular cells (HepG2), colorectal carcinoma cells (HT-29), and normal keratinocytes (HaCaT). Cells were treated with SDEMI for 4 and 24 h, then were assayed for levels of apoptosis, caspase-3, and Bcl-2 by flow cytometry, immunostaining, and Western blot, respectively. Significant differences between groups were determined using analysis of variance (P < 0.05). For HepG2 and HT-29 cells treated with SDEMI, various cytotoxic effects were observed compared with control cells at all timepoints assayed (P < 0.001). Furthermore, positive caspase-3 staining and down-regulation of Bcl-2 were observed, consistent with the induction of cell death detected in these cell lines. In contrast, treatment of HaCaT cells with SDEMI was associated with a protective effect compared with control cells at both timepoints (P < 0.001). For example, increased expression of Bcl-2 and negative caspase-3 staining were detected. Taken together, these results suggest that SDEMI protects normal cells, while SDEMI mediates induction of apoptosis via down-regulation of Bcl-2 and involvement of caspase-3 in human carcinoma cells.

  10. Emblica officinalis extract induces autophagy and inhibits human ovarian cancer cell proliferation, angiogenesis, growth of mouse xenograft tumors.

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    Alok De

    Full Text Available Patients with ovarian cancer (OC may be treated with surgery, chemotherapy and/or radiation therapy, although none of these strategies are very effective. Several plant-based natural products/dietary supplements, including extracts from Emblicaofficinalis (Amla, have demonstrated potent anti-neoplastic properties. In this study we determined that Amla extract (AE has anti-proliferative effects on OC cells under both in vitro and in vivo conditions. We also determined the anti-proliferative effects one of the components of AE, quercetin, on OC cells under in vitro conditions. AE did not induce apoptotic cell death, but did significantly increase the expression of the autophagic proteins beclin1 and LC3B-II under in vitro conditions. Quercetin also increased the expression of the autophagic proteins beclin1 and LC3B-II under in vitro conditions. AE also significantly reduced the expression of several angiogenic genes, including hypoxia-inducible factor 1α (HIF-1α in OVCAR3 cells. AE acted synergistically with cisplatin to reduce cell proliferation and increase expression of the autophagic proteins beclin1 and LC3B-II under in vitro conditions. AE also had anti-proliferative effects and induced the expression of the autophagic proteins beclin1 and LC3B-II in mouse xenograft tumors. Additionally, AE reduced endothelial cell antigen - CD31 positive blood vessels and HIF-1α expression in mouse xenograft tumors. Together, these studies indicate that AE inhibits OC cell growth both in vitro and in vivo possibly via inhibition of angiogenesis and activation of autophagy in OC. Thus AE may prove useful as an alternative or adjunct therapeutic approach in helping to fight OC.

  11. Lipido-sterolic extract of Serenoa repens (LSESr, Permixon) treatment affects human prostate cancer cell membrane organization.

    Science.gov (United States)

    Petrangeli, E; Lenti, L; Buchetti, B; Chinzari, P; Sale, P; Salvatori, L; Ravenna, L; Lococo, E; Morgante, E; Russo, A; Frati, L; Di Silverio, F; Russo, M A

    2009-04-01

    The molecular mechanism by which the lipido-sterolic extract of Serenoa repens (LSESr, Permixon) affects prostate cells remains to be fully elucidated. In androgen-independent PC3 prostate cancer cells, the LSESr-induced effects on proliferation and apoptosis were evaluated by counting cells and using a FACScan cytofluorimeter. PC3 cells were stained with JC-1 dye to detect mitochondrial membrane potential. Cell membrane lipid composition was evaluated by thin layer chromatography and gas chromatographic analysis. Akt phosphorylation was analyzed by Western blotting and cellular ultrastructure through electron microscopy. LSESr (12.5 and 25 microg/ml) administration exerted a biphasic action by both inhibiting proliferation and stimulating apoptosis. After 1 h, it caused a marked reduction in the mitochondrial potential, decreased cholesterol content and modified phospholipid composition. A decrease in phosphatidylinositol-4,5-bisphosphate (PIP2) level was coupled with reduced Akt phosphorylation. After 24 h, all of these effects were restored to pre-treatment conditions; however, the saturated (SFA)/unsaturated fatty acid (UFA) ratio increased, mainly due to a significant decrease in omega 6 content. The reduction in cholesterol content could be responsible for both membrane raft disruption and redistribution of signaling complexes, allowing for a decrease of PIP2 levels, reduction of Akt phosphorylation and apoptosis induction. The decrease in omega 6 content appears to be responsible for the prolonged and more consistent increase in the apoptosis rate and inhibition of proliferation observed after 2-3 days of LSESr treatment. In conclusion, LSESr administration results in complex changes in cell membrane organization and fluidity of prostate cancer cells that have progressed to hormone-independent status. (c) 2008 Wiley-Liss, Inc.

  12. Ethanolic extract of Descurainia sophia seeds sensitizes A549 human lung cancer cells to TRAIL cytotoxicity by upregulating death receptors.

    Science.gov (United States)

    Park, Jong-Shik; Lim, Chae Jun; Bang, Ok-Sun; Kim, No Soo

    2016-04-02

    Our previous genome-wide gene expression analysis revealed that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptors 4 (DR4) and 5 (DR5) are markedly upregulated by the ethanolic extract of D. sohia seeds (EEDS) in A549 TRAIL-refractory cancer cells. In the present study, we investigated whether the EEDS-mediated upregulation of TRAIL death receptors was associated with increased TRAIL-mediated toxicity in A549 cells in vitro. Cell proliferation and viability were determined by an automatic cell counter. Gene silencing was performed by introducing small interfering RNA into cells. Expression changes of cellular proteins were determined by western blot analysis. Apoptotic cell death was monitored by western blot analysis. Analysis of variance followed by the post-hoc Dunnett's test was used to compare the data. EEDS treatment increased both mRNA and protein levels of DR4 and DR5 in the TRAIL refractory A549 cells. Co-treatment of A549 cells with sub-lethal dose of EEDS and recombinant TRAIL increased the apoptotic cell death. Upregulation of DR5 by EEDS was mediated by an endoplasmic reticulum stress-induced transcription factor, CCAAT/enhancer-binding protein homologous protein (CHOP), and knockdown of CHOP expression inhibited EEDS-induced DR5 upregulation and abolished the EEDS-associated increase in TRAIL toxicity in A549 cells. EEDS can sensitize A549 cells to TRAIL cytotoxicity by upregulation of TRAIL death receptors. Our findings suggested that EEDS is a good initial herbal source for the development of an anticancer supplement for anticancer therapeutics associated with TRAIL.

  13. Herbal Extract SH003 Suppresses Tumor Growth and Metastasis of MDA-MB-231 Breast Cancer Cells by Inhibiting STAT3-IL-6 Signaling

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    Youn Kyung Choi

    2014-01-01

    Full Text Available Cancer inflammation promotes cancer progression, resulting in a high risk of cancer. Here, we demonstrate that our new herbal extract, SH003, suppresses both tumor growth and metastasis of MDA-MB-231 breast cancer cells via inhibiting STAT3-IL-6 signaling path. Our new herbal formula, SH003, mixed extract from Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii Maximowicz, suppressed MDA-MB-231 tumor growth and lung metastasis in vivo and reduced the viability and metastatic abilities of MDA-MB-231 cells in vitro. Furthermore, SH003 inhibited STAT3 activation, which resulted in a reduction of IL-6 production. Therefore, we conclude that SH003 suppresses highly metastatic breast cancer growth and metastasis by inhibiting STAT3-IL-6 signaling path.

  14. Antioxidant and Cytotoxic Effect of Barringtonia racemosa and Hibiscus sabdariffa Fruit Extracts in MCF-7 Human Breast Cancer Cell Line.

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    Amran, Norliyana; Rani, Anis Najwa Abdul; Mahmud, Roziahanim; Yin, Khoo Boon

    2016-01-01

    The fruits of Barringtonia racemosa and Hibiscus sabdariffa have been used in the treatment of abscess, ulcer, cough, asthma, and diarrhea as traditional remedy. This study aims to evaluate cytotoxic effect of B. racemosa and H. sabdariffa methanol fruit extracts toward human breast cancer cell lines (MCF-7) and its antioxidant activities. Total antioxidant activities of extracts were assayed using 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH) and β-carotene bleaching assay. Content of phytochemicals, total flavonoid content (TFC), and total phenolic content (TPC) were determined using aluminum chloride colorimetric method and Folin-Ciocalteu's reagent, respectively. Cytotoxic activity in vitro was investigated through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. B. racemosa extract exhibited high antioxidant activities compared to H. sabdariffa methanol fruit extracts in DPPH radical scavenging assay (inhibitory concentration [IC50] 15.26 ± 1.25 μg/mL) and ί-carotene bleaching assay (I% 98.13 ± 1.83%). B. racemosa also showed higher TPC (14.70 ± 1.05 mg gallic acid equivalents [GAE]/g) and TFC (130 ± 1.18 mg quercetin equivalents [QE]/g) compared to H. sabdariffa (3.80 ± 2.13 mg GAE/g and 40.75 ± 1.15 mg QE/g, respectively). In MTT assay, B. racemosa extract also showed a higher cytotoxic activity (IC50 57.61 ± 2.24 μg/mL) compared to H. sabdariffa. The present study indicated that phenolic and flavonoid compounds known for oxidizing activities indicated an important role among the contents of these plants extract. B. racemosa methanol extract have shown potent cytotoxic activity toward MCF-7. Following these promising results, further fractionation of the plant extract is underway to identify important phytochemical bioactives for the development of potential nutraceutical and pharmaceutical use. The phenolic and flavonoid compounds were present in B. racemosa and H. sabdariffa methanol extractsB. racemosa methanol

  15. Radiation-induced DNA Double Strand Breaks and Their Modulations by Treatments with Moringa oleifera Lam. Leaf Extracts: A Cancer Cell Culture Model

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    K. Boonsirichai

    2014-04-01

    Full Text Available Gamma radiation brings deleterious effects upon human cells by inducing oxidative stress and DNA damages. Antioxidants have been shown to confer protective effects on irradiated normal cells. Moringa oleifera Lam. is a widely used nutritional supplement with antioxidant activities. This report showed that antioxidant-containing supplements, in addition to protecting normal cells, could protect cancer cells against genotoxic effects of gamma radiation. -H2AX immunofluorescent foci were utilized as an indicator of radiation-induced DNA double strand breaks. MCF-7 human breast adenocarcinoma cells were irradiated with 2-8 Gy gamma radiation. A linear relationship between the formation of -H2AX foci and radiation dose was observed with an average of 10 foci per cell per Gy. A 30-minute pretreatment of the cells with either the aqueous or the ethanolic extract of M. oleifera leaves could partially protect the cells from radiation-induced DNA double strand breaks. A pretreatment with 500 µg/mL aqueous extract reduced the number of foci formed by 15% when assayed at 30 minutes post-irradiation. The ethanolic extract was more effective; 500 µg/mL of its concentration reduced the number of foci among irradiated cells by 30%. The results indicated that irradiated cancer cells responded similarly to nutritional supplements containing antioxidants as irradiated normal cells. These natural antioxidants could confer protective effects upon cancer cells against gamma radiation

  16. Antioxidant Activity and ROS-Dependent Apoptotic Effect of Scurrula ferruginea (Jack Danser Methanol Extract in Human Breast Cancer Cell MDA-MB-231.

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    Mohsen Marvibaigi

    Full Text Available Scurrula ferruginea (Jack Danser is one of the mistletoe species belonging to Loranthaceae family, which grows on the branches of many deciduous trees in tropical countries. This study evaluated the antioxidant activities of S. ferruginea extracts. The cytotoxic activity of the selected extracts, which showed potent antioxidant activities, and high phenolic and flavonoid contents, were investigated in human breast cancer cell line (MDA-MB-231 and non-cancer human skin fibroblast cells (HSF-1184. The activities and characteristics varied depending on the different parts of S. ferruginea, solvent polarity, and concentrations of extracts. The stem methanol extract showed the highest amount of both phenolic (273.51 ± 4.84 mg gallic acid/g extract and flavonoid contents (163.41 ± 4.62 mg catechin/g extract and strong DPPH• radical scavenging (IC50 = 27.81 μg/mL and metal chelation activity (IC50 = 80.20 μg/mL. The stem aqueous extract showed the highest ABTS•+ scavenging ability. The stem methanol and aqueous extracts exhibited dose-dependent cytotoxic activity against MDA-MB-231 cells with IC50 of 19.27 and 50.35 μg/mL, respectively. Furthermore, the extracts inhibited the migration and colony formation of MDA-MB-231 cells in a concentration-dependent manner. Morphological observations revealed hallmark properties of apoptosis in treated cells. The methanol extract induced an increase in ROS generation and mitochondrial depolarization in MDA-MB-231 cells, suggesting its potent apoptotic activity. The present study demonstrated that the S. ferruginea methanol extract mediated MDA-MB-231 cell growth inhibition via induction of apoptosis which was confirmed by Western blot analysis. It may be a potential anticancer agent; however, its in vivo anticancer activity needs to be investigated.

  17. Antiproliferative effect of the Ginkgo biloba extract is associated with the enhancement of cytochrome P450 1B1 expression in estrogen receptor-negative breast cancer cells

    Science.gov (United States)

    ZHAO, XIAO-DAN; DONG, NI; MAN, HONG-TAO; FU, ZHONG-LIN; ZHANG, MEI-HONG; KOU, SHUANG; MA, SHI-LIANG

    2013-01-01

    Ginkgo biloba is a dioecious tree and its extract is a complex mixture that has been used for thousands of years to treat a variety of ailments in traditional Chinese medicine. The aim of this study was to present our observations on the inhibitory effects of different Ginkgo biloba extracts on human breast cancer cell proliferation and growth. Our results demonstrated that treatment of MCF-7 and MDA-MB-231 human breast cancer cells with Ginkgo biloba leaves and ginkgo fruit extract inhibited cell proliferation. It was also observed that this inhibition was accompanied by the enhancement of cytochrome P450 (CYP) 1B1 expression in MDA-MB-231 cells. In addition, treatment with ginkgo fruit extract resulted in a higher CYP1B1 expression in MDA-MB-231 cells compared to treatment with the Ginkgo biloba leaves extract. Our results suggested that the inhibitory effects of the Ginkgo biloba extract on estrogen receptor-negative breast cancer proliferation and the induction of CYP1B1 expression may be exerted through an alternative pathway, independent of the estrogen receptor or the aryl hydrocarbon receptor pathway. PMID:24649031

  18. Induction of apoptosis and oxidative stress in estrogen receptor-negative breast cancer, MDA-MB231 cells, by ethanolic mango seed extract

    OpenAIRE

    Abdullah, Al-Shwyeh Hussah; Mohammed, Abdulkarim Sabo; Rasedee, Abdullah; Mirghani, Mohamed Elwathig Saeed; Al-Qubaisi, Mothanna Sadiq

    2015-01-01

    Background In this study, the effect of mango kernel extract in the induction of apoptosis of the breast cancer (MDA-MB-231) cell line was examined. This is an attempt to discover alternatives to current therapeutic regimes in the treatment of breast cancers. Methods The pro-apoptotic markers, Bax, cytochrome c, caspases-. -8 and ?9, and anti-apoptotic markers, Bcl-2, p53 and glutathione were determined in MDA-MB231 cells treated for 12 and 24?h with mango kernel extract. Results The results ...

  19. Huaier extract enhances the treatment efficacy of paclitaxel in breast cancer cells via the NF-κB/IκBα pathway.

    Science.gov (United States)

    Yang, Liu; Song, Zhenchuan; Wang, Xinle; Yang, Wei; Wang, Meiqi; Liu, Huan

    2017-12-01

    Breast cancer is considered as the most common malignant disease in women. Huaier extract, a type of traditional Chinese medicine, has been found to have antitumor activity. In the present study, we aimed to investigate whether the combined treatments of paclitaxel and Huaier extract may improve treatment efficacy in breast cancer cells. Human breast cancer cell lines MCF-7 and MDA-MB-231 were used to evaluate the antitumor efficacy of Huaier extract and paclitaxel both in vitro and in vivo. Using proliferation assays and flow cytometry, we found that both Huaier extract and paclitaxel decreased cell viability and induced cell apoptosis in a time- and dose-dependent manner. The combined treatments were more effective than monotherapy. Huaier extract induced cycle arrest in the G0/G1 phase, and paclitaxel arrested the cell cycle in the G2/M phase. Furthermore, the results of real-time PCR and western blotting revealed that Huaier extract decreased p65 and c-Met expression and increased IκBα expression, while paclitaxel increased p65 expression and reduced IκBα and c-Met expression. Consistent with the in vitro results, both Huaier extract and paclitaxel exerted a significant inhibitory effect on xenografted tumor growth, and the combined therapies revealed the most marked inhibitory effect. Collectively, our results indicated that Huaier extract increased the antitumor effect of paclitaxel therapy in breast cancer cells. The molecular mechanisms may be involved in the inhibition of the NF-κB pathway and c-Met expression.

  20. [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.

  1. Pharmacological screening of bryophyte extracts that inhibit growth and induce abnormal phenotypes in human HeLa cancer cells.

    Science.gov (United States)

    Krzaczkowski, Lucie; Wright, Michel; Rebérioux, Delphine; Massiot, Georges; Etiévant, Chantal; Gairin, Jean Edouard

    2009-08-01

    Antitumor activities of substances from natural sources apart from vascular plants and micro-organisms have been poorly investigated. Here we report on a pharmacological screening of a bryophyte extract library using a phenotypic cell-based assay revealing microtubules, centrosomes and DNA. Among the 219 moss extracts tested, we identified 41 extracts acting on cell division with various combinations of significant effects on interphasic and mitotic cells. Seven extracts were further studied using a cell viability assay, cell cycle analysis and the phenotypic assay. Three distinct pharmacological patterns were identified including two unusual phenotypes.

  2. Differential effect of grape seed extract against human non-small-cell lung cancer cells: the role of reactive oxygen species and apoptosis induction.

    Science.gov (United States)

    Tyagi, Alpna; Raina, Komal; Gangar, Subhash; Kaur, Manjinder; Agarwal, Rajesh; Agarwal, Chapla

    2013-01-01

    The present study examines grape seed extract (GSE) efficacy against a series of non-small-cell lung cancer (NSCLC) cell lines that differ in their Kras and p53 status to establish GSE potential as a cytotoxic agent against a wide range of lung cancer cells. GSE suppressed growth and induced apoptotic death in NSCLC cells irrespective of their k-Ras status, with more sensitivity toward H460 and H322 (wt k-Ras) than A549 and H1299 cells (mutated k-Ras). Mechanistic studies in A549 and H460 cells, selected, based on comparative efficacy of GSE at higher and lower doses, respectively, showed that apoptotic death involves cytochrome c release associated caspases 9 and 3 activation, and poly (ADP-ribosyl) polymerase cleavage, strong phosphorylation of ERK1/2 and JNK1/2, downregulation of cell survival proteins, and upregulated proapoptotic Bak expression. Importantly, GSE treatment caused a strong superoxide radical-associated oxidative stress, significantly decreased intracellular reduced glutathione levels, suggesting, for the first time, the involvement of GSE-caused oxidative stress in its apoptotic inducing activity in these cells. Because GSE is a widely-consumed dietary agent with no known untoward effects, our results support future studies to establish GSE efficacy and usefulness against NSCLC control.

  3. The effect of ethanolic extract of Thymus kotschyanus on cancer cell growth in vitro and depression-like behavior in the mouse

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    Mohammad-Hossein Doosti

    2018-01-01

    Full Text Available Cancer and depression are known as two of the most debilitating disease and disorder increasing evidence suggest an urgent need for new therapeutic agents with lower toxicity and high efficacy. Some Thyme species extracts have remarkably been shown to positively affect depression and cancer cells. In the present study, we investigated the effect of Thymus kotschyanus on depression and cancer cells. To this end, in experiment 1, NMRI mice were treated orally with the ethanolic extract of T. kotschyanus (50, 150 and 250 mg/ml for seven days and then depression-like behavior was measured by Forced Swim Test (FST and Tail Suspension Test (TST. In experiment 2, the pharmacological effect of the extract on the lung (A549 and cervical (Hela cancer cell lines was also evaluated by MTT (3-(4,5-Dimethylthiazol-2-Yl-2,5-Diphenyltetrazolium Bromide in various concentration_(10, 5, 2.5, 1.25, 0.63, 0.31, 0.15 and 0.08 mg/ml. The results indicated that T. kotschyanus extract treatment (150 and 250 mg/kg decreased depression-like behavior in the FST and TST tests in adult mice. Moreover, the treatment inhibited cancer cell growth and viability in a dose and time-dependent manner. Collectively these findings suggest that T. kotschyanus have antidepressant and anticancer effects.

  4. In Vitro Antiproliferative Effect of Arthrocnemum indicum Extracts on Caco-2 Cancer Cells through Cell Cycle Control and Related Phenol LC-TOF-MS Identification

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    Mondher Boulaaba

    2013-01-01

    Full Text Available This study aimed to determinate phenolic contents and antioxidant activities of the halophyte Arthrocnemum indicum shoot extracts. Moreover, the anticancer effect of this plant on human colon cancer cells and the likely underlying mechanisms were also investigated, and the major phenols were identified by LC-ESI-TOF-MS. Results showed that shoot extracts had an antiproliferative effect of about 55% as compared to the control and were characterised by substantial total polyphenol content (19 mg GAE/g DW and high antioxidant activity (IC50=40 μg/mL for DPPH test. DAPI staining revealed that these extracts decrease DNA synthesis and reduce the proliferation of Caco-2 cells which were stopped at the G2/M phase. The changes in the cell-cycle-associated proteins (cyclin B1, p38, Erk1/2, Chk1, and Chk2 correlate with the changes in cell cycle distribution. Eight phenolic compounds were also identified. In conclusion, A. indicum showed interesting antioxidant capacities associated with a significant antiproliferative effect explained by a cell cycle blocking at the G2/M phase. Taken together, these data suggest that A. indicum could be a promising candidate species as a source of anticancer molecules.

  5. Coix lacryma-jobi var. ma-yuen Stapf sprout extract has anti-metastatic activity in colon cancer cells in vitro.

    Science.gov (United States)

    Son, Eun Suk; Kim, Young Ock; Park, Chun Geon; Park, Kyung Hun; Jeong, Sung Hwan; Park, Jeong-Woong; Kim, Se-Hee

    2017-11-06

    Coix lacryma-jobi var. ma-yuen (Rom.Caill.) Stapf has been used in China as an herbal medicine. Many studies of this plant have reported anti-proliferative and apoptotic activities on human cancer cell lines. Therefore, this study of the anti-metastatic effect of Coix lacryma-jobi var. ma-yuen Stapf sprout extract (CLSE) in colorectal cancer cells may provide a scientific basis for exploring anti-cancer effects of edible crops. To evaluate the effect of CLSE on cell proliferation and signaling, we performed a Cell Counting Kit-8 (CCK-8) assay in HCT116 cells and used western blot analysis. Furthermore, scratch-wound healing, transwell migration, matrigel invasion, and adhesion assays were conducted to elucidate the anti-metastatic effects of CLSE under hypoxic conditions in colon cancer cells. First, CLSE decreased deferoxamine (DFO)-induced migration of colon cancer cells by 87%, and blocked colon cancer cell migration by 80% compared with hypoxia control cells. Second, CLSE treatment resulted in a 54% reduction in hypoxia-induced invasiveness of colon cancer cells, and 50% inhibition of adhesive potency through inactivation of the extracellular signal-regulated kinase (ERK) 1/2 and protein kinase b (AKT) pathways. Third, conditioned medium collected from CLSE-treated HCT116 cells suppressed tube formation of human umbilical vein endothelial cells (HUVECs) by 91%. CLSE inhibited migration, invasion, and adhesion of colon cancer cells and tube formation by HUVECs via repression of the ERK1/2 and AKT pathways under hypoxic conditions. Therefore, CLSE may be used to treat patients with colon cancer.

  6. Ethanolic extract of Thevetia peruviana flowers enhances TNF-α and TRAIL-induced apoptosis of human cervical cancer cells via intrinsic and extrinsic pathways

    Science.gov (United States)

    Managit, Chittima; Sakurai, Hiroaki; Saiki, Ikuo

    2017-01-01

    Tumor necrosis factor-α (TNF-α) and TNF-related apoptosis-inducing ligand (TRAIL) are promising candidates for cancer treatment due to their ability to induce apoptosis through death receptor stimulation. However, their usage may be limited due to the resistance of cancer cells to TNF-α- and TRAIL-induced apoptosis. Currently, there is interest in screening for natural products that can sensitize cancer cells to TNF-α- and TRAIL-induced apoptosis for their use in combination with TNF-α or TRAIL. It was previously reported that the bark extract of Thevetia peruviana showed a reversal effect on TRAIL-resistance in human gastric adenocarcinoma cell lines. In the present study, the effects of the ethanolic extract of T. peruviana flowers on TNF-α- and TRAIL-induced apoptosis of human cervical cancer HeLa cells were investigated in vitro by determining cell viability and apoptosis using a WST-1 cell proliferation assay and immunoblot analysis, respectively. The ethanolic extract of T. peruviana flowers promoted TNF-α and TRAIL-mediated cell death through the activation of the caspase cascade, poly(ADP-ribose) polymerase and BH3-interacting domain death agonist cleavage. Combined treatment using the extract plus TNF-α resulted in downregulation of anti-apoptotic protein, including myeloid cell leukemia sequence-1, B-cell lymphoma-extra large (Bcl-XL), X-linked inhibitor of apoptosis protein and survivin, while the combined treatment with TRAIL downregulated Bcl-XL. Thus, the ethanolic extract of T. peruviana flowers has potential in sensitizing the TNF-α- and TRAIL-induced apoptosis of HeLa cells via the intrinsic and extrinsic pathways. PMID:28454468

  7. Piper nigrum ethanolic extract rich in piperamides causes ROS overproduction, oxidative damage in DNA leading to cell cycle arrest and apoptosis in cancer cells.

    Science.gov (United States)

    de Souza Grinevicius, Valdelúcia Maria Alves; Kviecinski, Maicon Roberto; Santos Mota, Nádia Sandrini Ramos; Ourique, Fabiana; Porfirio Will Castro, Luiza Sheyla Evenni; Andreguetti, Rafaela Rafognato; Gomes Correia, João Francisco; Filho, Danilo Wilhem; Pich, Claus Tröger; Pedrosa, Rozangela Curi

    2016-08-02

    Ayurvedic and Chinese traditional medicine and tribal people use herbal preparations containing Piper nigrum fruits for the treatment of many health disorders like inflammation, fever, asthma and cancer. In Brazil, traditional maroon culture associates the spice Piper nigrum to health recovery and inflammation attenuation. The aim of the current work was to evaluate the relationship between reactive oxygen species (ROS) overproduction, DNA fragmentation, cell cycle arrest and apoptosis induced by Piper nigrum ethanolic extract and its antitumor activity. The plant was macerated in ethanol. Extract constitution was assessed by TLC, UV-vis and ESI-IT-MS/MS spectrometry. The cytotoxicity, proliferation and intracellular ROS generation was evaluated in MCF-7 cells. DNA damage effects were evaluated through intercalation into CT-DNA, plasmid DNA cleavage and oxidative damage in CT-DNA. Tumor growth inhibition, survival time increase, apoptosis, cell cycle arrest and oxidative stress were assessed in Ehrlich ascites carcinoma-bearing mice. Extraction yielded 64mg/g (36% piperine and 4.2% piperyline). Treatments caused DNA damage and reduced cell viability (EC50=27.1±2.0 and 80.5±6.6µg/ml in MCF-7 and HT-29 cells, respectively), inhibiting cell proliferation by 57% and increased ROS generation in MCF-7 cells (65%). Ehrlich carcinoma was inhibited by the extract, which caused reduction of tumor growth (60%), elevated survival time (76%), cell cycle arrest and induced apoptosis. The treatment with extract increased Bax and p53 and inhibited Bcl-xL and cyclin A expression. It also induced an oxidative stress in vivo verified as enhanced lipid peroxidation and carbonyl proteins content and increased activities of glutathione reductase, superoxide dismutase and catalase. GSH concentration was decreased in tumor tissue from mice. The ethanolic extract has cytotoxic and antiproliferative effect on MCF-7 cells and antitumor effect in vivo probably due to ROS overproduction

  8. Targeting Colorectal Cancer Proliferation, Stemness and Metastatic Potential Using Brassicaceae Extracts Enriched in Isothiocyanates: A 3D Cell Model-Based Study

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    Lucília P. Pereira

    2017-04-01

    Full Text Available Colorectal cancer (CRC recurrence is often attributable to circulating tumor cells and/or cancer stem cells (CSCs that resist to conventional therapies and foster tumor progression. Isothiocyanates (ITCs derived from Brassicaceae vegetables have demonstrated anticancer effects in CRC, however little is known about their effect in CSCs and tumor initiation properties. Here we examined the effect of ITCs-enriched Brassicaceae extracts derived from watercress and broccoli in cell proliferation, CSC phenotype and metastasis using a previously developed three-dimensional HT29 cell model with CSC-like traits. Both extracts were phytochemically characterized and their antiproliferative effect in HT29 monolayers was explored. Next, we performed cell proliferation assays and flow cytometry analysis in HT29 spheroids treated with watercress and broccoli extracts and respective main ITCs, phenethyl isothiocyanate (PEITC and sulforaphane (SFN. Soft agar assays and relative quantitative expression analysis of stemness markers and Wnt/β-catenin signaling players were performed to evaluate the effect of these phytochemicals in stemness and metastasis. Our results showed that both Brassicaceae extracts and ITCs exert antiproliferative effects in HT29 spheroids, arresting cell cycle at G2/M, possibly due to ITC-induced DNA damage. Colony formation and expression of LGR5 and CD133 cancer stemness markers were significantly reduced. Only watercress extract and PEITC decreased ALDH1 activity in a dose-dependent manner, as well as β-catenin expression. Our research provides new insights on CRC therapy using ITC-enriched Brassicaceae extracts, specially watercress extract, to target CSCs and circulating tumor cells by impairing cell proliferation, ALDH1-mediated chemo-resistance, anoikis evasion, self-renewal and metastatic potential.

  9. Fractionated Ocimum gratissimum leaf extract inhibit prostate cancer (PC3·AR) cells growth by reducing androgen receptor and survivin levels.

    Science.gov (United States)

    Ekunwe, Stephen I; Hall, Sakeli M; Luo, Xuan; Wang, Hengshan; Begonia, Gregorio B

    2013-11-01

    In this study, the antiproliferative activity of the organic solvent-soluble and aqueous extracts of Ocimum gratissimum leaf against the prostate cancer cells PC3·AR were evaluated by their inhibitory effects on the Androgen Receptor (AR) and Survivin protein. Two organic solvent-soluble extracts P2 and P3-2, and a water- soluble extract, PS/PT1, were found to reduce AR and Survivin levels in a time-dependent manner. In addition, extract PS/PT1, also exhibited the inhibitory activity in a dose-dependent manner. This is the first time that the inhibitory eff ects of O. gratissimum extracts have been evaluated on the Androgen Receptor (AR) and Survivin protein. The results encouraged the further studies of O. gratissimum as a potential treatment of prostate cancer.

  10. Investigating migration inhibition and apoptotic effects of Fomitopsis pinicola chloroform extract on human colorectal cancer SW-480 cells.

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    Yaqin Wang

    Full Text Available BACKGROUND: Fomitopsis pinicola (Sw. Ex Fr.m Karst (FPK which belongs to the Basidiomycota fungal class is one of the most popular medical fungi in China. It has been used for many diseases: cancer, heart diseases, diabetes and so on. However, little study on the pro-apoptotic effect and migration inhibition of FPK chloroform extract (FPKc has been reported and the possible involved mechanism has not been illuminated. METHODOLOGY/PRINCIPAL FINDINGS: Chemical analysis was performed by HPLC which showed ergosterol (ES concentration was 105 µg/mg. MTT assay revealed that FPKc could selectively inhibit SW-480 cells viability with the IC50 of 190.28 µg/ml. Wound healing and transwell assay indicated that FPKc could inhibit the migration of SW-480 cells obviously, FPKc could also dramatically decreased the matrix metalloproteinases-2, 9 (MMP-2 and MMP-9 expression. Annexin V-FITC/PI staining, nuclear Hoechst 33342 staining and DNA fragmentation analysis revealed that FPKc and ES could induce SW-480 cells apoptosis. The apoptosis process closely involved in ROS accumulation and depletion of GSH, activation of caspase 3, poly (ADP-ribose polymerase (PARP degradation. FPKc could also up-regulate P53 expression and thus lead to G1 phase arrest. When SW-480 cells were pretreated with N-acetylcysteine (NAC, the ROS generation, cell viability and apoptotic ratio were partially declined, which indicated that ROS was vertical in the pro-apoptosis process induced by FPKc. Moreover, in the whole process, ES which has been previously found in FPKc had the similar effect to FPKc. Thus we could conclude that ES, as one of the highest abundant components in FPKc, might also be one of the active constituents. CONCLUSION/SIGNIFICANCE: FPKc could inhibit the migration of SW-480 cells, induce SW-480 cells G1 phase arrest and cause ROS-mediated apoptosis effect. And ES might be one of the effective constituents in the whole process.

  11. The in vitro effect of Viscum album (VA) extract on DNA repair of peripheral blood mononuclear cells (PBMC) in cancer patients.

    Science.gov (United States)

    Kovacs, Eva

    2002-03-01

    Viscum album (VA) extract as an immunomodulator was tested in an in vitro model to investigate DNA repair in damaged peripheral blood mononuclear cells (PBMC) of ten breast cancer patients. The cells were exposed by gamma rays or 4-hydroxycyclophosphamide (4-HCy). Two hours after exposure the following were measured, without or with VA extract (1) DNA repair using the alkaline sucrose gradient for the sedimentation of DNA strand breaks, (2) DNA-gamma-production in the supernatant of the cultured cells. The VA extract led to an improvement of DNA repair in gamma-ray or 4-HCy damaged PBMC and to a significant increase of the IFN-gamma-production both in undamaged and in damaged cells. The results indicate that the VA extract affects positively DNA repair in PBMC damaged by two different agents and suggest that an increased IFN-gamma-production may play an important role in the DNA repair process. Copyright 2002 John Wiley & Sons, Ltd.

  12. Lycopene Extracts from Different Tomato-Based Food Products Induce Apoptosis in Cultured Human Primary Prostate Cancer Cells and Regulate TP53, Bax and Bcl-2 Transcript Expression

    Science.gov (United States)

    Soares, Nathalia da Costa Pereira; Machado, Clara Lima; Trindade, Bruno Boquimpani; Lima, Ingridy Celestino do Canto; Gimba, Etel Rodrigues Pereira; Teodoro, Anderson Junger; Takiya, Christina; Borojevic, Radovan

    2017-01-01

    Carotenoids are the main tomato components, especially lycopene. Lycopene is more bioavailable in tomato processed products than in raw tomatos, since formation of lycopene cis-isomers during food processing and storage may increase its biological activity. In the current study, we evaluated the influence of lycopene extracts (5 mg / mL) from different tomato-based food products (paste, sauce, extract and ketchup) on cell viability and apoptosis on primary human prostate cancer cells (PCa cels) for 96h. Using MTT assay, we observed a significant decrease on primary PCa cell viability upon treatment with lycopene extracted from either 4 tomato-based food products. Flow cytometeric analysis revealed that lycopene from tomato extract and tomato sauce promoted up to fifty-fold increase on the proportion of apoptotic cells, when compared to the control group. Using real time PCR assay, we found that lycopene promoted an upregulation of TP53 and Bax transcript expression and also downregulation of Bcl-2 expression in PCa cells. In conclusion, our data demostrate that cis-lycopene promoted a significant inhibition on primary PCa cell viability, as well as an increase on their apoptotic rates, evidencing that cis-lycopene contained in tomato sauce and extract cain mainly modulate of primary human prostate cancer cell survival. PMID:28345329

  13. A comparison of the gene expression profiles and pathway network analyses after treatment of Prostate cancer cell lines with different Ganoderma lucidum based extracts.

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    Chi H.J. Kao

    2014-05-01

    Full Text Available Background: Ganoderma lucidum is a type of fungus commonly consumed in Asia for the promotion of health and longevity. The observed biological activity of G. lucidum includes anti-cancer and anti-inflammatory effects which may be useful in the treatment and prevention of cancer and other chronic diseases. G. lucidum grows under conditions which range from tropical to temperate and has a different physiology depending on the geographical region in which it is grown. For this reason, the health benefits may vary depending on the form of G. lucidum and the environmental conditions to which it was exposed. This led us to investigate the effect of wildly grown G. lucidum, from the Himalayan region versus other commercially available G. lucidum products, on two human cancer cell lines. Methods: Extraction of the bioactive components found in G. lucidum is essential, as the fungus is tough and indigestible. Four different Ganoderma extracts were prepared. Thereafter, the extracts were tested on two human prostate cancer cell lines, and the IC50s were determined. This was followed by the use of Affymetrix GeneChip® PrimeView™ Human Gene Expression Arrays to identify the changes in gene expression due to the treatment of prostate cancer cell lines (PC3 and DU145 with Ganoderma extracts. Several key genes identified with Affymetrix analysis were validated using RT-PCR. Results and Discussion: We found that all the Ganoderma extracts showed growth inhibition in the cancer cell lines tested. Using Affymetrix microarray analysis, we identified four main biologically active pathways: cell cycle control/apoptosis, cell-cell adhesion, DNA repair, and inflammatory /immune response, where activity was influenced by the Ganoderma extracts used. Using RT-PCR, we tested ten genes associated with all four pathways. The RT-PCR results supported our findings in the Affymetrix analysis, i.e. that G. lucidum extracts have an anti-inflammatory and cell cycle effect and

  14. IC 50 of Ganoderma lucidum extract on oral cancer cells, ORL-48T ...

    African Journals Online (AJOL)

    ... and Malaysia ranked 14 in the world for oral cancer incidence. Despite recent advancement in treatment modalities, the prognosis and survival rates for oral cancer patients have not improved significantly over the past decades. Ganodermalucidum has long been used in Chinese traditional and conventional medicine for ...

  15. The anticancer potential of steroidal saponin, dioscin, isolated from wild yam (Dioscorea villosa) root extract in invasive human breast cancer cell line MDA-MB-231 in vitro

    Science.gov (United States)

    Previously, we observed that wild yam (Dioscorea villosa) root extract (WYRE) was able to activate GATA3 in human breast cancer cells targeting epigenome. This study aimed to 'nd out if dioscin (DS), a bioactive compound of WYRE, can modulate GATA3 functions and cellular invasion in human breast can...

  16. Grape seed extract dose-responsively decreases disease severity in a rat model of mucositis; concomitantly enhancing chemotherapeutic effectiveness in colon cancer cells.

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    Ker Yeaw Cheah

    Full Text Available OBJECTIVE: Mucositis is a serious disorder of the gastrointestinal tract that results from cancer chemotherapy. We investigated the effects of increasing grape seed extract doses on the severity of chemotherapy in a rat model and its coincident impact on chemotherapeutic effectiveness in colon cancer cells. DESIGN: Female Dark Agouti rats were gavaged with grape seed extract (400-1000 mg/kg or water (day 3-11 and were injected intraperitoneally with 5-Fluorouracil (150 mg/kg or saline (control on day 9 to induce mucositis. Daily metabolic data were collected and rats were sacrificed on day 12. Intestinal tissues were collected for histological and myeloperoxidase analyses. Caco-2 cell viability was examined in response to grape seed extract in combination with 5-Fluorouracil by 3-(4,5-Dimethylthiazol-2yl-2,5-diphenyl-tetrazolium bromide assay. RESULTS: Compared with 5-Fluorouracil controls, grape seed extract (400-1000 mg/kg significantly decreased the histological damage score (P<0.05 in the jejunum. Grape seed extract (1000 mg/kg increased jejunal crypt depth by 25% (P<0.05 in 5-Fluorouracil treated rats compared to 5-Fluorouracil controls, and attenuated the 5-Fluorouracil -induced reduction of mucosal thickness (25%, P<0.05. Grape seed extract (600 mg/kg decreased myeloperoxidase activity by 55% (P<0.01 compared to 5-Fluorouracil controls. Grape seed extract was more effective at ameliorating 5-Fluorouracil induced intestinal injury, with effects most pronounced in the proximal jejunum. Grape seed extract (10-25 ug/mL significantly enhanced the growth-inhibitory effects of 5-Fluorouracil by 26% (P<0.05 in Caco-2 cells and was more potent than 5-Fluorouracil at 50-100 µg/mL. CONCLUSION: Grape seed extract may represent a new therapeutic option to decrease the symptoms of intestinal mucositis while concurrently impacting on the viability of colon cancer cells.

  17. Rhodiola rosea extracts and salidroside decrease the growth of bladder cancer cell lines via inhibition of the mTOR pathway and induction of autophagy.

    Science.gov (United States)

    Liu, Zhongbo; Li, Xuesen; Simoneau, Anne R; Jafari, Mahtab; Zi, Xiaolin

    2012-03-01

    The incidence of human urinary bladder cancer increases markedly with age, suggesting a mechanistic connection between aging and bladder carcinogenesis and a potential use of anti-aging agents in bladder cancer chemoprevention. Rhodiola rosea, growing in high altitude or cold regions of the world, has been reported to have anti-aging effects in Drosophila. We demonstrated that a R. rosea extract and one of its bioactive components, salidroside, inhibited the growth of bladder cancer cell lines with a minimal effect on nonmalignant bladder epithelial cells TEU-2. Interestingly, the R. rosea extract and salidroside component exhibited a selective ability to inhibit the growth of p53 knockout primary mouse embryo fibroblasts (p53-/- MEFs) compared to their wild-type counterparts. The growth inhibitory effects of the R. rosea extract and salidroside were, however, attenuated in TSC2 and p53 double knock MEFs (TSC2-/-, p53-/- MEFs), suggesting that TSC2 protein is, at least in part, required for the growth inhibitory effects of the R. rosea extract and salidroside. The R. rosea extract and salidroside treatment of UMUC3 cells resulted in an increase of AMP-activated protein kinase (AMPK)-α phosphorylation and a decrease of 4E-BP1 phosphorylation, leading to increased binding of 4E-BP1 to m7 GTP. These results indicate that the R. rosea extract and salidroside inhibit translation initiation. Furthermore, both the R. rosea extract and salidroside treatment of UMUC3 cells caused a significant percentage of cells undergoing autophagy. Therefore, the R. rosea extract and salidroside deserve further study as novel agents for chemoprevention of bladder carcinogenesis. Copyright © 2011 Wiley Periodicals, Inc.

  18. The Effect of Crude Extract of Pandanus conoideus Lamb. var. Yellow Fruit on Apoptotic Expression of the Breast Cancer Cell Line (T47D

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    OKID PARAMA ASTIRIN

    2009-01-01

    Full Text Available A mechanism controlling a growing cancer cells is by a programmed cell death (apoptosis. The wildtype-p53 enable to stop cleaves that follow DNA repair or cell death (apoptosis. The mutation of wt-p53 caused loosing its ability to inhibit cancer cells proliferation. Healing methods like surgery, radiation, immunotherapy and chemotherapy still have some weaknesses, and clinical medicine to cancer is also still has any dissatisfactory. Much of chemotherapy was not given optimal result yet, because no specific action to cancer cells only, but also to the normal cells. These problems encourage important effort to find specific and sensitive anticancer. Empirical evidence indicates that the crude extract of Pandanus conoideus Lamb var. yellow fruit has potential effect as an anticancer. Method of Freshney was used in growing T47D cell line, counting cells was done by direct counting, and apoptotic evaluation was done by TUNEL enzymatic labeling assay. The results of the research demonstrated that the LC50 of yellow fruit extract are 0.25 µL/mL. The percentage of apoptotic of 0.125 µL/mL, 0.0625 µL/mL, and 0.03125 µL/mL are 34.38±2.26, 30.03±3.87 and 21.07±1.14 respectively.

  19. Ginkgo biloba extract decreases non-small cell lung cancer cell migration by downregulating metastasis-associated factor heat-shock protein 27.

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    Jong-Rung Tsai

    Full Text Available Heat-shock proteins (HSPs are molecular chaperones that protect proteins from damage. HSP27 expression is associated with cancer transformation and invasion. Ginkgo biloba extract (EGb761, the most widely sold herbal supplement, has antiangiogenic effects and induces tumor apoptosis. Data regarding the effect of EGb761 on HSP expression is limited, particularly in cancer. HSP27 expression in paired tumors and normal lung tissues of 64 patients with non-small cell lung cancer (NSCLC were detected by real-time PCR, western blotting, and immunohistochemistry. NSCLC cell lines (A549/H441 were used to examine the migratory abilities in vitro. NSCLC tissue showed higher HSP27 expression than normal lung tissue. Kaplan-Meier survival analysis showed that NSCLC patients with low HSP27 expression ratio (1 (p = 0.04. EGb761 inhibited HSP27 expression and migratory ability of A549/H441 cells, which is the same as HSP27-siRNA transfection effect. Moreover, EGb761 treatment activated the AKT and p38 pathways and did not affect the expression of PI3K, ERK, and JNK pathways. HSP27 is a poor prognostic indicator of NSCLC. EGb761 can decrease the migration ability of A549/H441 by inhibiting HSP27 expression most likely through AKT and p38 MAPK pathways activation.

  20. Ethyl Acetate Extracts of Semen Impatientis Inhibit Proliferation and Induce Apoptosis of Human Prostate Cancer Cell Lines through AKT/ERK Pathways.

    Science.gov (United States)

    Wang, Tao; Cai, Yang; Song, Wen; Chen, Ruibao; Hu, Dunmei; Ye, Jianhan; Liu, Lu; Peng, Wei; Zhang, Junfeng; Wang, Shaogang; Yang, Weiming; Liu, Jihong; Ding, Yufeng

    2017-01-01

    Objective. To investigate the inhibitory effect of ethyl acetate extracts of Impatiens balsamina L. on prostate cancer cells. Methods. Impatiens balsamina L. was extracted to get water, ethanol, oil ether, ethyl acetate, and butanol extracts. CCK-8 assay was used to detect the inhibitory effect. Apoptosis rates and cell cycle distribution were detected by flow cytometry. Transwell assay was performed to test the ability of migration. The expressions of Bcl-2, Bax, cleaved-caspase-3, p-ERK, ERK, p-AKT, AKT, cyclin D1, cyclin E, and MMP2 were detected by Western blot. Results. Ethyl acetate extracts had the strongest inhibitory effect. After being treated with different concentrations of ethyl acetate extracts, the percentage of G0/G1 phase increased significantly, cyclin D1 and cyclin E expression decreased, apoptosis rate was significantly higher, and the ability of migration of PC-3 and RV1 was inhibited significantly. Western blot showed that the expressions of Bcl-2, p-ERK, and p-AKT were significantly decreased, but the expressions of Bax and caspase-3 cleavage were increased. Conclusions. Impatiens balsamina L. inhibited the proliferation of human prostate cancer cells; ethyl acetate extracts have the strongest effect. It could inhibit cell proliferation and migration, cause G1 phase arrest, and induce apoptosis probably through inhibition of the AKT and ERK pathways.

  1. Anticancer Potential of Aqueous Ethanol Seed Extract of Ziziphus mauritiana against Cancer Cell Lines and Ehrlich Ascites Carcinoma

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    Tulika Mishra

    2011-01-01

    Full Text Available Ziziphus mauritiana (Lamk. is a fruit tree that has folkloric implications against many ailments and diseases. In the present study, anticancer potential of seed extract of Ziziphus mauritiana in vitro against different cell lines (HL-60, Molt-4, HeLa, and normal cell line HGF by MTT assay as well as in vivo against Ehrich ascites carcinoma bearing Swiss albino mice was investigated. The extract was found to markedly inhibit the proliferation of HL-60 cells. Annexin and PI binding of treated HL-60 cells indicated apoptosis induction by extract in a dose-dependent manner. The cell cycle analysis revealed a prominent increase in sub Go population at concentration of 20 μg/ml and above. Agarose gel electrophoresis confirmed DNA fragmentation in HL-60 cells after 3 h incubation with extract. The extract also exhibited potent anticancer potential in vivo. Treatment of Ehrlich ascites carcinoma bearing Swiss albino mice with varied doses (100–800 mg/kg b.wt. of plant extract significantly reduced tumor volume and viable tumor cell count and improved haemoglobin content, RBC count, mean survival time, tumor inhibition, and percentage life span. The enhanced antioxidant status in extract-treated animals was evident from decline in levels of lipid peroxidation and increased levels of glutathione, catalase, and superoxide dismutase.

  2. Bio-guided fractionation of methanol extract of Ziziphus mauritiana Lam. (bark and effect of the most active fraction on cancer cell lines

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    Richard Simo Tagne

    2015-04-01

    Full Text Available Objective: To investigate the anticancer and antioxidant potential of methanol bark extract of Ziziphus mauritiana (Z. mauritiana, which is used by traditional healers to cure some cases of cancer in Cameroon. Methods: The methanol crude extract of Z. mauritiana has the antiproliferative activity on four cancer cell lines and its antioxidant activity. The extract was partitioned in five different solvents, and each fraction was tested. The effect of the most antiproliferative fraction on cell cycle was determined. Bio-guided fractionation was performed on the fraction with the highest antiproliferative and the highest antioxidant activities. Results: Z. mauritiana methanol extract was active on all tested cells, and showed promising antioxidant activity. All fractions except hexane fraction were active with the dichloromethane fraction being the most active and showed S and G2-M phase arrest (P<0.01 on cell cycle progression of NCI-H460 and MCF-7, respectively. Bio-guided fractionation of the dichloromethane fraction led to lupeol and betulinic acid. The greatest antioxidant activity was recorded with ethyl acetate fraction and its fractionation led to catechin and epigallocatechin. Conclusions: Overall, this study showed that Z. mauritiana barks has benefits as a chemoprevention agent cancer.

  3. Cytotoxicity of methanol extracts ofAnnona muricata,Passiflora edulisand nine other Cameroonian medicinal plants towards multi-factorial drug-resistant cancer cell lines.

    Science.gov (United States)

    Kuete, Victor; Dzotam, Joachim K; Voukeng, Igor K; Fankam, Aimé G; Efferth, Thomas

    2016-01-01

    Cancer cells rapidly acquire resistance leading to treatment failures. In the present study, we have evaluated the cytotoxicity of 17 methanol extracts from 11 Cameroonian medicinal plants against the sensitive leukemia CCRF-CEM cells and the best ones were further tested on a panel of 8 other human cancer cell lines, including various MDR phenotypes as well as against the normal AML12 hepatocytes. The cytotoxicity of the extracts was determined using a resazurin reduction assay meanwhile flow cytometry was used to measure cell cycle, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species. In an initial screening using leukemia CCRF-CEM cells, ten extracts from five plants namely Alchornea floribunda , Annona muricata , Euphorbia prostata , Pachypodanthium staudtii and Passiflora edulis displayed IC 50 values below 20 µg/mL. They were further tested in 8 other cell lines as well as in normal AML12 hepatocytes. All selected extracts were active against leukemia CEM/ADR5000 cells with IC 50 value below 40 µg/mL. IC 50 values ranging from 10.13 µg/mL (towards CEM/ADR5000 cells) to 72.01 µg/mL [towards resistant colon carcinoma HCT116 ( p53 - / - ) cells] for Pachypodanthium staudtii roots and from 0.11 µg/mL (towards CCRF-CEM cells) to 108 µg/mL (towards P-glycoprotein-over-expressing CEM/ADR5000 cells) for doxorubicin were obtained in the eight other cancer cell lines studied. Extracts from Annona muricata leaves (AML) and seeds (AMS), and Passiflora edulis fruit (PEF) had IC 50 values below 1 µg/mL against CCRF-CEM cells and below 10 µg/mL against its MDR subline CEM/ADR5000 cells. AML, AMS and PEF induced MMP-loss-mediated apoptosis in CCRF-CEM cells. Results of the present study suggest that some of the tested plants namely Alchornea floribunda , Annona muricata , Euphorbia prostata , Pachypodanthium staudtii and Passiflora edulis represent a source of anticancer drugs. Annona muricata and Passiflora edulis are good

  4. Antiproliferative activity and nitric oxide production of a methanolic extract of Fraxinus micrantha on Michigan Cancer Foundation-7 mammalian breast carcinoma cell line

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    Suresh Kumar

    2015-06-01

    Full Text Available Aim:Methanolic extract of aFraxinus micrantha(MeFM was evaluated for antiproliferative activity in vitrousing Michigan Cancer Foundation-7 (MCF-7 breast carcinoma cell line. This plant was selected and studied for naturally available bioactive compound as different synthetic drugs available for cancer treatment has certain limitations and side effects. Materials and Methods:The anti-proliferative activity of a methanolic extract from the aerial parts of F. micranthawas assessed on MCF-7 breast cancer cell line using 3(4,5-dimethylthiazol-2-yl2,5-diphenyl-tetrazolium bromide assay. Furthermore, to understand the mechanism of anti-proliferation, production of nitric oxide (NO and DNA fragmentation was also determined on MCF-7 cells. Different phytoconstituents of the extract were determined qualitatively based on various biochemical assays. Results: The results demonstrated anti-proliferative activity of an MeFM in a concentration and time-dependent manner. The percentage viability determined was 31.24% at 125 and #956;g/ml as compared to 80.46% in negative control group. An MeFM has also shown NO production in a concentration (0.2-125 and #956;g/ml and time-dependent manner (24-48 h. DNA fragmentation studies showed that a methanolic extract was causing DNA fragmentation thus inducing apoptosis in MCF-7 breast carcinoma cells. Biochemical analysis result showed the presence of flavonoids, polyphenols, and sterols in an MeFM. Conclusion:In conclusion, F. micranthapossesses potent anti-proliferative activity on the malignant MCF-7 cell line which is correlated with the production of NO and DNA fragmentation. Further studies are required to identify, isolate, and characterize the phytochemicals present in the methanolic extract that might have antiproliferative potential in the treatment of different cancer conditions. [J Intercult Ethnopharmacol 2015; 4(2.000: 109-113

  5. Evaluation of chemical composition, antioxidant, antibacterial, cytotoxic and apoptotic effects of Aloysia citrodora extract on colon cancer cell line using Real Time PCR and Flow-cytometry methods

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    Amir Mirzaie

    2016-06-01

    Full Text Available Background and aims: Aloysia citrodora belongs to the Verbenaceae family of plants, a well-known herbal medicine in Iran. The aim of the present study was to investigate the chemical composition, antioxidant, antibacterial, cytotoxic and apoptotic effect of A. citrodora extract against human colon cancer using real time PCR and flow cytometry methods. Materials and Methods: this experimental study was carried out in Islamic Azad University, East Tehran Branch, from March to September of 2014. At first, the A. citrodora chemical constituents were analyzed by GC/MS technique. In addition, antioxidant assay, antibacterial and anti-cancer effect was performed using DPPH, disk diffusion and MTT methods, respectively. Finally, the apoptosis gene (Bax and Bcl2 expression was performed by real time PCR and apoptotic effects was analyzed using Flow-cytometry technique. Results:  GC/MS analysis of A. citrodora extract was shown 37 major components and the most frequent component was belonged to Spathulenol (17.57% and Caryophyllene oxide (15.15%. The antioxidant activity of the extract was IC50=0.6 ±0.03. The maximum and minimum antibacterial effects of extract were belonged to Gram negative and Gram positive bacteria, respectively. Cytotoxic results revealed that the extract have IC50= 20.1± 0.78 mg/ml against colon cell line and Real Time PCR results showed the expression level of Bax and Bcl2 was increased and decreased respectively in colon cancer cell line (3.470 ± 0.72 (P<0.05, 0.43 ± 0.35 (P< 0.05. In addition, the flow-cytometry results indicated the 38.66 % apoptosis in colon cancer cell line. Conclusion: According to the results, it seems that A. citrodora extract has potential uses for pharmaceutical industries and it suggested that further studies were performed for A. citrodora pharmaceutical importance.

  6. Anticancer Activity of Chloroform Extract and Sub-fractions of Nepeta deflersiana on Human Breast and Lung Cancer Cells: An In vitro Cytotoxicity Assessment.

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    Al-Oqail, Mai M; Al-Sheddi, Ebtesam S; Siddiqui, Maqsood A; Musarrat, Javed; Al-Khedhairy, Abdulaziz A; Farshori, Nida N

    2015-10-01

    Cancer is one of the major causes of death worldwide. The plant-derived natural products have received considerable attention in recent years due to their diverse pharmacological properties including anticancer effects. Nepeta deflersiana (ND) is used in the folk medicine as antiseptic, carminative, antimicrobial, antioxidant, and for treating rheumatic disorders. However, the anticancer activity of ND chloroform extract has not been explored so far. The present study was aimed to investigate the anticancer activities of chloroform Nepeta deflersiana extract and various sub-fractions (ND-1-ND-15) of ND against human breast cancer cells (MCF-7) and human lung cancer cells (A-549). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and neutral red uptake assays, and cellular morphological alterations using phase contrast light microscope were studied. Cells were exposed with 10-1000 μg/ml of sub-fractions of ND for 24 h. Results showed that selected sub-fractions of the chloroform extract significantly reduced the cell viability of MCF-7 and A-549 cells, and altered the cellular morphology in a concentration-dependent manner. Among the sub-fractions, ND-10 fraction showed relatively higher cytotoxicity compared to other fractions whereas, ND-1 did not cause any cytotoxicity even at higher concentrations. The A-549 cells were found to be more sensitive to growth inhibition by all the extracts as compared to the MCF-7 cells. The present study provides preliminary screening of anticancer activities of chloroform extract and sub-fractions of ND, which can be further used for the development of a potential therapeutic anticancer agent. Nepeta deflersiana extract exhibit cytotoxicity and altered the cellular morphology. Sub-fractions of the chloroform extract of Nepeta deflersiana reduced the cell viability of MCF-7 and A-549 cells. Among the sub-fractions, ND-10 fraction showed relatively higher cytotoxicity. The A-549 cells were found to be more sensitive

  7. Alterations in Cell Cycle and Induction of Apoptotic Cell Death in Breast Cancer Cells Treated with α-Mangostin Extracted from Mangosteen Pericarp

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    Hitomi Kurose

    2012-01-01

    Full Text Available The development of molecularly targeted drugs has greatly advanced cancer therapy, despite these drugs being associated with some serious problems. Recently, increasing attention has been paid to the anticancer effects of natural products. α-Mangostin, a xanthone isolated from the pericarp of mangosteen fruit, has been shown to induce apoptosis in various cancer cell lines and to exhibit antitumor activity in a mouse mammary cancer model. In this study, we investigated the influence of α-mangostin on apoptosis and cell cycle in the human breast cancer cell line MDA-MB231 (carrying a p53 mutation, and HER2, ER, and PgR negative in order to elucidate its anticancer mechanisms. In α-mangostin-treated cells, induction of mitochondria-mediated apoptosis was observed. On cell-cycle analysis, G1-phase arrest, increased p21cip1 expression and decreases in cyclins, cdc(s, CDKs and PCNA were observed. In conclusion, α-mangostin may be useful as a therapeutic agent for breast cancer carrying a p53 mutation and having HER2- and hormone receptor-negative subtypes.

  8. The bioactive compounds alpha-chaconine and gallic acid in potato extracts decrease survival and induce apoptosis in LNCaP and PC3 prostate cancer cells.

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    Reddivari, Lavanya; Vanamala, Jairam; Safe, Stephen H; Miller, J Creighton

    2010-01-01

    We recently reported that colored potato extracts and an anthocyanin rich fraction suppressed lymph-node carcinoma of the prostate (LNCaP) and prostate cancer-3 (PC-3) prostate cancer cell proliferation and induced apoptosis via caspase-dependent and caspase-independent pathways. Chlorogenic acid, caffeic acid, gallic acid, catechin, malvidin, and glycoalkaloids (alpha-chaconine and solanine) have now been identified as the major bioactive components of potato, and their effects on LNCaP and PC-3 cell proliferation and apoptosis have been investigated. alpha-chaconine (5 microg/ml) and gallic acid (15 microg/ml) exhibited potent antiproliferative properties and increased cyclin-dependent kinase inhibitor p27 levels in both cell lines. Both alpha-chaconine and gallic acid induced poly [adenosine diphosphate (ADP)] ribose polymerase cleavage and caspase-dependent apoptosis in LNCaP cells; however, caspase-independent apoptosis through nuclear translocation of endonuclease G was observed in both LNCaP and PC-3 cells. alpha-chaconine and gallic acid activated c-Jun N-terminal protein kinase (JNK), and this response played a major role in induction of caspase-dependent apoptosis in LNCaP cells; whereas modulation of JNK and mitogen-activated protein kinase did not affect alpha-chaconine- and gallic acid-induced caspase-independent apoptosis. These results suggest that apoptosis induced by whole potato extracts in prostate cancer cell lines may be in part due to alpha-chaconine and gallic acid.

  9. Phytochemical composition, antibacterial and anticancer activities of Trifolium cherleri extract on lung cancer cell line (A549 and analysis of caspase 3 and caspase 9 apoptosis genes expression

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    Amir Mirzaie

    2017-08-01

    Methods: This experimental study was performed in Islamic Azad University, from December 2016 to February 2017. At first, the phytochemical constituents of T. cherleri extract were determined using gas chromatography-mass spectrometry (GC-MS method. Subsequently, the antibacterial activity of the extract was evaluated against some gram positive and negative pathogenic bacteria included Staphylococcus aureus ATCC 25923, Streptococcus pyogenes ATCC 19615, Salmonella enteritidis ATCC 13076 and Listeria monocytogenes ATCC 35152 via minimum inhibitory concentration (MIC method. Moreover, anticancer potential of extract was examined by colorimetric MTT assay toward lung cancer (A549 cell line. Then, the evaluation of caspase 3 and 9 apoptosis gene expression was determined using Real-Time Polymerase Chain Reaction (Real-Time PCR technique. Moreover, the Real-Time PCR was performed using relative quantitative method. Results: The phytochemical analyses of T. cherleri extract showed the 20 major components and the most frequent component was belonged to hexadecanoic acid, ethyl ester (20.7% and 2-Pentadecanone, 6,10,14-trimethyl (19.9%. The extract had maximum antibacterial effects against Staphylococcus aureus and Streptococcus pyogenes. There was a dose dependent increase in the cytotoxicity effect of extract against A549 cancer cell. Moreover, the Real-Time PCR results indicated that the caspase 3 and caspase 9 gene expression was significantly up-regulated 2.57±0.27 (P<0.05, and 3.3±0.46 (P<0.05, respectively. Conclusion: The results of this study showed that the T. cherleri extract had significant anti-bacterial and anti-cancer effects and it appear that the extract has potential uses for pharmaceutical industries. Moreover, it could be considered as a promising source for novel drug compounds, but more studies are needed.

  10. Cytotoxic activity of extracts and crude saponins from Zanthoxylum armatum DC. against human breast (MCF-7, MDA-MB-468) and colorectal (Caco-2) cancer cell lines.

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    Alam, Fiaz; Najum Us Saqib, Qazi; Waheed, Abdul

    2017-07-17

    Zanthoxylum armatum DC has been an important traditional plant known for its medicinal properties. It is well known for its antimicrobial, larvicidal and cytotoxic activities. The potential anticancer effects of the methanol extract and the crude saponins from fruit, bark and leaves of Z. armatum on breast (MDA-MB-468 and MCF-7) and colorectal (Caco-2) cancer cell lines using MTT, neutral red uptake(NRU) and DAPI stain assays were evaluated. In MTT assay the methanol extract of fruit (Zf), bark (Zb) and leaves (Zl) of Zanthoxylum armatum, showed significant and dose dependent growth inhibition of MCF-7, MDA MB-468 and Caco-2 cancer cell lines in a dose of 200 μg/ml and above. The saponins (Zf.Sa, Zb.Sa and Zl.Sa) showed significant activity against MDA MB-468 (95, 94.5 and 85.3%) as compared to MCF-7 (79.8, 9.43, 49.08%) and Caco-2 (75.8, 61.8, 68.62%) respectively. The extracts were further tested in more sensitive NRU assay and its was found that Zf extract showed higher cytotoxic activity as compared to Zb and Zl extracts with 100 μg/ml concentration. The breast cancer cell lines showed more sensitivity toward the crude saponins from fruit and bark with maximum inhibition of up to 93.81(±2.32) % with respect to 71.19(± 2.76) of Actinomycin-D. DAPI staining experiment showed that saponins from fruit induced apoptosis mode of cell death in all three types of cell lines while saponins form leaves and bark showed similar results against MDA MB-468 indicated by nuclear fragmentation and chromatin condensation. The effect of saponins from fruit, bark and leaves (Zf.Sa, Zb.Sa and Zl.Sa) against Caco-2 cell lines inhibited the growth of Caco-2 by 53.16 (±3.31) %, 66.43 (± 3.24) and 45.96 (± 10.67) respectively with respect to Actinomycin-D (4 μM) which showed the growth inhibition of 65.40(±4.29) %. The current study clearly demonstrates that the extract and crude saponins from fruit, bark and leaves of traditional medicinal plant Zanthoxyllum armatum DC

  11. Caffeic Acid Phenethyl Ester and Ethanol Extract of Propolis Induce the Complementary Cytotoxic Effect on Triple-Negative Breast Cancer Cell Lines

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    Anna Rzepecka-Stojko

    2015-05-01

    Full Text Available Chemotherapy of breast cancer could be improved by bioactive natural substances, which may potentially sensitize the carcinoma cells’ susceptibility to drugs. Numerous phytochemicals, including propolis, have been reported to interfere with the viability of carcinoma cells. We evaluated the in vitro cytotoxic activity of ethanol extract of propolis (EEP and its derivative caffeic acid phenethyl ester (CAPE towards two triple-negative breast cancer (TNBC cell lines, MDA-MB-231 and Hs578T, by implementation of the MTT and lactate dehydrogenase (LDH assays. The morphological changes of breast carcinoma cells were observed following exposure to EEP and CAPE. The IC50 of EEP was 48.35 µg∙mL−1 for MDA-MB-23 cells and 33.68 µg∙mL−1 for Hs578T cells, whereas the CAPE IC50 was 14.08 µM and 8.01 µM for the MDA-MB-231 and Hs578T cell line, respectively. Here, we report that propolis and CAPE inhibited the growth of the MDA-MB-231 and Hs578T lines in a dose-dependent and exposure time-dependent manner. EEP showed less cytotoxic activity against both types of TNBC cells. EEP and, particularly, CAPE may markedly affect the viability of breast cancer cells, suggesting the potential role of bioactive compounds in chemoprevention/chemotherapy by potentiating the action of standard anti-cancer drugs.

  12. Cigarette smoke extract induces epithelial-mesenchymal transition of human bladder cancer T24 cells through activation of ERK1/2 pathway.

    Science.gov (United States)

    Sun, Xin; Deng, Qifei; Liang, Zhaofeng; Liu, Zhiqi; Geng, Hao; Zhao, Li; Zhou, Qirui; Liu, Jie; Ma, Jiaxing; Wang, Daming; Yu, Dexin; Zhong, Caiyun

    2017-02-01

    Bladder cancer is a common genitourinary malignant disease worldwide. Abundant evidence has shown that cigarette smoke (CS) is a crucial risk factor for bladder cancer. Nevertheless, the mechanism underlying the relationship between cigarette smoking and bladder cancer remains unclear. In the present study, we investigated the effects of cigarette smoke extract (CSE) on mitogen-activated protein kinase (MAPK) pathway activation and EMT alterations in human bladder cancer T24 cells, and the preventive effect of extracellular regulated protein kinases 1 and 2 (ERK1/2) inhibitor U0126 was further examined. Our results illustrated that CSE exposure induced morphological change of human bladder cancer T24 cells, enhanced migratory and invasive capacities, reduced epithelial marker expression and elevated mesenchymal marker expression. Meanwhile, exposure of T24 cells to CSE resulted in activation of ERK1/2 pathway as well as activator protein 1 (AP-1) proteins. Interestingly, treatment with ERK1/2 inhibitor U0126 effectively abrogated CSE-triggered EMT and ERK1/2/AP-1 activation. These findings provide novel insight into the molecular mechanisms of CS-associated bladder cancer and may open up new avenues in the search for potential target of bladder cancer intervention. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Galectin-3-independent Down-regulation of GABABR1 due to Treatment with Korean Herbal Extract HAD-B Reduces Proliferation of Human Colon Cancer Cells

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    Kim Kyung-Hee

    2012-09-01

    Full Text Available Objectives: Many efforts have shown multi-oncologic roles of galectin-3 for cell proliferation, angiogenesis, and apoptosis. However, the mechanisms by which galectin-3 is involved in cell proliferation are not yet fully understood, especially in human colon cancer cells. Methods: To cluster genes showing positively or negatively correlated expression with galectin-3, we employed human colon cancer cell lines, SNU-61, SNU-81, SNU-769B, SNU-C4 and SNU-C5 in high-throughput gene expression profiling. Gene and protein expression levels were determined by using real-time quantitative polymerase chain reaction (PCR and western blot analysis, respectively. The proliferation rate of human colon cancer cells was measured by using a 3-(4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide (MTT assay. Results: Expression of γ-aminobutyric acid B receptor 1 (GABABR1 showed a positive correlation with galectin-3 at both the transcriptional and the translational levels. Downregulation of galectin-3 decreased not only GABABR1 expression but also the proliferation rate of human colon cancer cells. However, Korean herbal extract, HangAmDan-B (HAD-B, decreased expression of GABABR1 without any expressional change of galectin-3, and offset γ-aminobutyric acid (GABA-enhanced human colon cancer cell proliferation. Conclusions: Our present study confirmed that GABABR1 expression was regulated by galectin-3. HAD-B induced galectin-3-independent down-regulation of GABABR1, which resulted in a decreased proliferation of human colon cancer cells. The therapeutic effect of HAD-B for the treatment of human colon cancer needs to be further validated.

  14. The Acetone Extract of Sclerocarya birrea (Anacardiaceae) Possesses Antiproliferative and Apoptotic Potential against Human Breast Cancer Cell Lines (MCF-7)

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    Tanih, Nicoline Fri; Ndip, Roland Ndip

    2013-01-01

    Interesting antimicrobial data from the stem bark of Sclerocarya birrea, which support its use in traditional medicine for the treatment of many diseases, have been delineated. The current study was aimed to further study some pharmacological and toxicological properties of the plant to scientifically justify its use. Anticancer activity of water and acetone extracts of S. birrea was evaluated on three different cell lines, HT-29, HeLa, and MCF-7 using the cell titre blue viability assay in 96-well plates. Apoptosis was evaluated using the acridine orange and propidium iodide staining method, while morphological structure of treated cells was examined using SEM. The acetone extract exhibited remarkable antiproliferative activities on MCF-7 cell lines at dose- and time-dependent manners (24 h and 48 h of incubation). The extract also exerted apoptotic programmed cell death in MCF-7 cells with significant effect on the DNA. Morphological examination also displayed apoptotic characteristics in the treated cells, including clumping, condensation, and culminating to budding of the cells to produce membrane-bound fragmentation, as well as formation of apoptotic bodies. The acetone extract of S. birrea possesses antiproliferative and apoptotic potential against MCF-7-treated cells and could be further exploited as a potential lead in anticancer therapy. PMID:23576913

  15. Nucleic acid extraction from formalin-fixed paraffin-embedded cancer cell line samples: a trade off between quantity and quality?

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    Seiler, Caroline; Sharpe, Alan; Barrett, J Carl; Harrington, Elizabeth A; Jones, Emma V; Marshall, Gayle B

    2016-01-01

    Advanced genomic techniques such as Next-Generation-Sequencing (NGS) and gene expression profiling, including NanoString, are vital for the development of personalised medicines, as they enable molecular disease classification. This has become increasingly important in the treatment of cancer, aiding patient selection. However, it requires efficient nucleic acid extraction often from formalin-fixed paraffin-embedded tissue (FFPE). Here we provide a comparison of several commercially available manual and automated methods for DNA and/or RNA extraction from FFPE cancer cell line samples from Qiagen, life Technologies and Promega. Differing extraction geometric mean yields were evaluated across each of the kits tested, assessing dual DNA/RNA extraction vs. specialised single extraction, manual silica column based extraction techniques vs. automated magnetic bead based methods along with a comparison of subsequent nucleic acid purity methods, providing a full evaluation of nucleic acids isolated. Out of the four RNA extraction kits evaluated the RNeasy FFPE kit, from Qiagen, gave superior geometric mean yields, whilst the Maxwell 16 automated method, from Promega, yielded the highest quality RNA by quantitative real time RT-PCR. Of the DNA extraction kits evaluated the PicoPure DNA kit, from Life Technologies, isolated 2-14× more DNA. A miniaturised qPCR assay was developed for DNA quantification and quality assessment. Careful consideration of an extraction kit is necessary dependent on quality or quantity of material required. Here we provide a flow diagram on the factors to consider when choosing an extraction kit as well as how to accurately quantify and QC the extracted material.

  16. Chrysin, Abundant in Morinda citrifolia Fruit Water-EtOAc Extracts, Combined with Apigenin Synergistically Induced Apoptosis and Inhibited Migration in Human Breast and Liver Cancer Cells.

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    Huang, Cheng; Wei, Yu-Xuan; Shen, Ma-Ching; Tu, Yu-Hsuan; Wang, Chia-Chi; Huang, Hsiu-Chen

    2016-06-01

    The composition of Morinda citrifolia (M. citrifolia) was determined using high-performance liquid chromatography (HPLC), and the anticancer effects of M. citrifolia extract evaluated in HepG2, Huh7, and MDA-MB-231 cancer cells. M. citrifolia fruit extracts were obtained by using five different organic solvents, including hexane (Hex), methanol (MeOH), ethyl acetate (EtOAc), chloroform (CHCl3), and ethanol (EtOH). The water-EtOAc extracts from M. citrifolia fruits was found to have the highest anticancer activity. HPLC data revealed the predominance of chrysin in water-EtOAc extracts of M. citrifolia fruit. Furthermore, the combined effects of cotreatment with apigenin and chrysin on liver and breast cancer were investigated. Treatment with apigenin plus chrysin for 72-96 h reduced HepG2 and MDA-MB-231 cell viability and induced apoptosis through down-regulation of S-phase kinase-associated protein-2 (Skp2) and low-density lipoprotein receptor-related protein 6 (LRP6) expression. However, the combination treatment for 36 h synergistically decreased MDA-MB-231 cell motility but not cell viability through down-regulation of MMP2, MMP9, fibronectin, and snail in MDA-MB-231 cells. Additionally, chrysin combined with apigenin also suppressed tumor growth in human MDA-MB-231 breast cancer cells xenograft through down-regulation of ki-67 and Skp2 protein. The experimental results showed that chrysin combined with apigenin can reduce HepG2 and MDA-MB-231 proliferation and cell motility and induce apoptosis. It also offers opportunities for exploring new drug targets, and further investigations are underway in this regard.

  17. Hericium erinaceus (Lion’s Mane) mushroom extracts inhibit metastasis of cancer cells to the lung in CT-26 colon cancer-transplanted mice

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    We investigated the anti-metastatic activity of four Hericium erinaceus edible mushroom extracts using CT-26 murine colon carcinoma cells as an indicator of inhibition of cell migration to the lung. Hot water (HWE) and microwaved 50% ethanol (MWE) extracts of Hericium erinaceus strongly elicited ca...

  18. Soy milk digestion extract inhibits progression of prostate cancer cell growth via regulation of prostate cancer‑specific antigen and cell cycle-regulatory genes in human LNCaP cancer cells.

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    Kang, Nam-Hee; Shin, Hee-Chang; Oh, Seunghyun; Lee, Kyun-Hee; Lee, Yoon-Bok; Choi, Kyung-Chul

    2016-08-01

    Soy milk, which is produced from whole soybeans, contains a variety of biologically active components. Isoflavones are a class of soy-derived phytoestrogens with beneficial effects, among which genistein (GEN) has been previously indicated to reduce the risk of prostate cancer. The present study evaluated the effects of soy milk digestion extract (SMD) on the progression of prostate cancer via the estrogen receptor (ER)β in human LNCaP prostate cancer cells. To evaluate the effects of SMD (daizein, 1.988 mg/100g, glycitein, 23.537 mg/100 g and GEN, 0.685 mg/100g) on cell proliferation, LNCaP cells were cultured in media containing vehicle (0.1% dimethyl sulfoxide), 17β‑estradiol (E2; 2.7x10‑7 mg/ml), GEN (2.7x10-2 mg/ml) of SMD (total aglycon concentration, 0.79 mg/ml), after which the cell viability was examined using an MTT assay. The cell viability was significantly elevated by E2 (by 45±0.18%), while it was markedly reduced by GEN (73.2±0.03%) or SMD (74.8±0.09%). Semi‑quantitative reverse transcription polymerase chain reaction analysis was performed to assess the mRNA expression levels of target genes, including ERβ, prostate cancer‑specific antigen (PSA) and cell cycle regulators p21, Cyclin D1 and cyclin-dependent kinase (CDK)4. The expression of ERβ was almost completely diminished by E2, whereas it was significantly elevated by SMD. In addition, the expression levels of PSA were considerably reduced by SMD. The expression of p21 was significantly elevated by SMD, while it was markedly reduced by E2. Of note, the expression levels of Cyclin D1 and CDK4 were considerably elevated by E2, while being significantly reduced by GEN and SMD. All of these results indicated that SMD may inhibit the proliferation of human prostate cancer cells via regulating the expression of ERβ, PSA, p21, Cyclin D1 and CDK4 in an ER-dependent manner.

  19. Epithelial-mesenchymal transition and cancer stem cells, mediated by a long non-coding RNA, HOTAIR, are involved in cell malignant transformation induced by cigarette smoke extract

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    Liu, Yi; Luo, Fei; Xu, Yuan; Wang, Bairu; Zhao, Yue; Xu, Wenchao; Shi, Le; Lu, Xiaolin; Liu, Qizhan, E-mail: drqzliu@hotmail.com

    2015-01-01

    The incidence of lung diseases, including cancer, caused by cigarette smoke is increasing, but the molecular mechanisms of gene regulation induced by cigarette smoke remain unclear. This report describes a long noncoding RNA (lncRNA) that is induced by cigarette smoke extract (CSE) and experiments utilizing lncRNAs to integrate inflammation with the epithelial-mesenchymal transition (EMT) in human bronchial epithelial (HBE) cells. The present study shows that, induced by CSE, IL-6, a pro-inflammatory cytokine, leads to activation of STAT3, a transcription activator. A ChIP assay determined that the interaction of STAT3 with the promoter regions of HOX transcript antisense RNA (HOTAIR) increased levels of HOTAIR. Blocking of IL-6 with anti-IL-6 antibody, decreasing STAT3, and inhibiting STAT3 activation reduced HOTAIR expression. Moreover, for HBE cells cultured in the presence of HOTAIR siRNA for 24 h, the CSE-induced EMT, formation of cancer stem cells (CSCs), and malignant transformation were reversed. Thus, IL-6, acting on STAT3 signaling, which up-regulates HOTAIR in an autocrine manner, contributes to the EMT and to CSCs induced by CSE. These data define a link between inflammation and EMT, processes involved in the malignant transformation of cells caused by CSE. This link, mediated through lncRNAs, establishes a mechanism for CSE-induced lung carcinogenesis. - Highlights: • STAT3 directly regulates the levels of LncRNA HOTAIR. • LncRNA HOTAIR mediates the link between inflammation and EMT. • LncRNA HOTAIR is involved in the malignant transformation of cells caused by CSE.

  20. TheEffect of bevacizumab and hydroalcohlic Extract of Matricaria chamomilla on cell viability and nitric oxide production of the colorectal cancer cell line (HT-29

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    N Danaei

    2016-03-01

    Full Text Available Background & aim: Angiogenesis is associated with tumor growth and metastasis of tumor cells, this processes directly linked with the production of nitric oxide. In this study anticancer effects of hydroalcohoic extract of M. chamomilla and avastin (bevacizumab were investigated via dimethyl thiazol diphenyltetrazolium bromide (MTT cell viability assay and nitric oxide (NO production level in colon cancer cell line (HT-29. Methods: In the present experimental study, the HT-29 cell line was cultured in RPMI-1640 media supplemented with 10% (v/v fetal bovine serum (FBS, 1% antibiotic solution (consisting of100 U/mL penicillin and 100 µg/ml streptomycin. After growing to a favorite confluent, 104cells were seeded into separate 96-well culture microtiter plates and incubated at 370C in an incubator with 5% CO2 for 24 h prior to treatment. Every plate was treated with different   concentrations of the extract (1000, 1400, 1800, 2200, 2600 µg/ml of medium and bevacizumab (100,200,300 µg/ml.  The production of NO was assessed by Griess reagent and the cell viability was determined by MTT assay. The results were compared by one-way ANOVA followed by Tukey-Kramer. Result: The results of MTT assay indicated that the extract and bevacizumab anticancer effect is time and dose dependent. The highest percentage of cell death was observed after 48 h incubation which increased in the bevacizumab concentration (P<0.01. Fifty percent inhibitory concentration (IC50 of extract in 24 h and 48h was 1881 and 1669 µg/ml, respectively. Inhibition of nitric oxide (NO production was maximum in 2600 µg/ml extract concentration.                                                                                                                                               Conclusion: The results of the present study demonstrated

  1. Evaluation of antioxidative and antitumor activities of extracted flavonoids from Pink Lady apples in human colon and breast cancer cell lines.

    Science.gov (United States)

    Yang, Shufang; Zhang, Haisheng; Yang, Xingbin; Zhu, Yilin; Zhang, Min

    2015-12-01

    The antioxidative and anticancer effects of extracted flavonoids from Pink Lady apples on human colon cancer LoVo cells and breast cancer MCF-7 cells were evaluated. It was found that the antioxidative property of the peel-flavonoids (Peel-F) was more effective than that of the flesh-flavonoids (Flesh-F). Meanwhile, both the Peel-F and Flesh-F can inhibit cancer cell growth in a dose-dependent manner, with the IC50 values of 110.33 ± 2.52 mg mL(-1) and 378.14 ± 1.64 mg mL(-1) for LoVo cells and 58.42 ± 1.39 mg mL(-1) and 296.06 ± 3.71 mg mL(-1) for MCF-7 cells. This led to the conclusion that the Peel-F were more effective against cancer cells than the Flesh-F, and that the scavenging ROS effects were significantly higher in the Peel-F in vitro. Moreover, we also found that the generation of ROS is a critical mediator in apple flavonoid-induced cell apoptosis and the induction effect of the Peel-F was significantly higher than that of the Flesh-F.

  2. Combined ginger extract & Gelam honey modulate Ras/ERK and PI3K/AKT pathway genes in colon cancer HT29 cells.

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    Tahir, Analhuda Abdullah; Sani, Nur Fathiah Abdul; Murad, Noor Azian; Makpol, Suzana; Ngah, Wan Zurinah Wan; Yusof, Yasmin Anum Mohd

    2015-04-01

    The interconnected Ras/ERK and PI3K/AKT pathways play a central role in colorectal tumorigenesis, and they are targets for elucidating mechanisms involved in attempts to induce colon cancer cell death. Both ginger (Zingiber officinale) and honey have been shown to exhibit anti-tumor and anti-inflammation properties against many types of cancer, including colorectal cancer. However, there are currently no reports showing the combined effect of these two dietary compounds in cancer growth inhibition. The aim of this study was to evaluate the synergistic effect of crude ginger extract and Gelam honey in combination as potential cancer chemopreventive agents against the colorectal cancer cell line HT29. The cells were divided into 4 groups: the first group represents HT29 cells without treatment, the second and third groups were cells treated singly with either ginger or Gelam honey, respectively, and the last group represents cells treated with ginger and Gelam honey combined. The results of MTS assay showed that the IC50 of ginger and Gelam honey alone were 5.2 mg/ml and 80 mg/ml, respectively, whereas the IC50 of the combination treatment was 3 mg/ml of ginger plus 27 mg/ml of Gelam honey with a combination index of ginger and Gelam honey treatment was associated with the stimulation of early apoptosis (upregulation of caspase 9 and IκB genes) accompanied by downregulation of the KRAS, ERK, AKT, Bcl-xL, NFkB (p65) genes in a synergistic manner. In conclusion, the combination of ginger and Gelam honey may be an effective chemopreventive and therapeutic strategy for inducing the death of colon cancer cells.

  3. Differential growth inhibition of cancer cell lines and antioxidant activity of extracts of red, brown, and green marine algae.

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    Murugan, Kavitha; Iyer, Vidhya V

    2013-05-01

    As the use of various anticancer drugs is associated with many undesirable side effects, there is an urgent need for the discovery of new, better, and specific anticancer compounds. Antioxidant and antiproliferative activities as well as effects on cell morphology were investigated for methanol (M), chloroform (C), ethyl acetate (E), and aqueous (A) extracts of Caulerpa peltata, Gelidiella acerosa, Padina gymnospora, and Sargassum wightii using 2,2-diphenyl-1-picrylhydrazyl radical-scavenging, ferrous ion chelation, and resazurin-based growth inhibition (in A549, HCT-15, MG-63, and PC-3 cell lines) assays. A general trend was the greater extraction of phenols and flavonoids by chloroform and ethyl acetate, which showed higher activity in many assays. These non-polar C and E extracts showed higher DPPH radical-scavenging and growth inhibitory activities in A549, HCT-15, and PC-3 cells. However, higher ferrous ion chelation (A extracts) and growth inhibition in MG-63 cells (M and A extracts) were seen for the polar extracts. Furthermore, P. gymnospora and C. peltata emerged as promising sources for antiproliferative agents that could be explored for their own activity and as leads for the development of other compounds.

  4. The Inhibitory Effect of C-phycocyanin Containing Protein Extract (C-PC Extract) on Human Matrix Metalloproteinases (MMP-2 and MMP-9) in Hepatocellular Cancer Cell Line (HepG2).

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    Kunte, Mugdha; Desai, Krutika

    2017-06-01

    Spirulina platensis :have been studied for several biological activities. In the current study C-phycocyanin containing protein extract (C-PC extract) of Spirulina platensis have been studied for its effect on human matrix metalloproteinases (MMP-1, MMP-2 and MMP-9) and tissue inhibitors of MMPs (TIMP-1 and TIMP-2). In the present study, breast cancer cell line (MDA-MB 231) and hepatocellular cancer cell line (HepG2) were examined for inhibition of MMPs at different levels of expression after C-PC extract treatment. Herein, we have demonstrated that C-PC extract significantly reduced activity of MMP-2 by 55.13% and MMP-9 by 57.9% in HepG2 cells at 15 μg concentration. Additionally, the treatment has reduced mRNA expression of MMP-2 and MMP-9 at 20 μg concentration by 1.65-folds and 1.66-folds respectively. The C-PC extract treatment have also downregulated a mRNA expression of TIMP-2 by 1.12 folds at 20 μg concentration in HepG2 cells. Together, these results indicate that C-PC, extract successfully inhibited MMP-2 and -9 at different levels of expression and TIMP-2 at a mRNA expression level; however, extract did not have any effect on MMP-1 expressed in MDA-MB231 and TIMP-1 expressed in HepG2 cells as well as the exact mechanism of inhibition of MMP-2, MMP-9 and TIMP-2 remained unclear.

  5. Anti-Inflammatory Effects of a Methanol Extract from the Marine Sponge Geodia cydonium on the Human Breast Cancer MCF-7 Cell Line

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    Susan Costantini

    2015-01-01

    Full Text Available Many research groups are working to find new possible anti-inflammatory molecules, and marine sponges represent a rich source of biologically active compounds with pharmacological applications. In the present study, we tested different concentrations of the methanol extract from the marine sponge, Geodia cydonium, on normal human breast epithelial cells (MCF-10A and human breast cancer cells (MCF-7. Our results show that this extract has no cytotoxic effects on both cell lines whereas it induces a decrease in levels of VEGF and five proinflammatory cytokines (CCL2, CXCL8, CXCL10, IFN-γ, and TNF-α only in MCF-7 cells in a dose-dependent manner, thereby indicating an anti-inflammatory effect. Moreover, interactomic analysis suggests that all six cytokines are involved in a network and are connected with some HUB nodes such as NF-kB subunits and ESR1 (estrogen receptor 1. We also report a decrease in the expression of two NFKB1 and c-Rel subunits by RT-qPCR experiments only in MCF-7 cells after extract treatment, confirming NF-kB inactivation. These data highlight the potential of G. cydonium for future drug discovery against major diseases, such as breast cancer.

  6. Investigation of Astragalus honey and propolis extract's cytotoxic effect on two human cancer cell lines and their oncogen and proapoptotic gene expression profiles.

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    Sadeghi-Aliabadi, Hojjat; Hamzeh, Jamal; Mirian, Mina

    2015-01-01

    Cancer is one of the major fatal human diseases. Natural products have been used in the treatment of cancer for long time. Bee products including honey and propolis have been introduced for malignancy treatment in recent decades. In this study cytotoxicity of bee products and their effects on the expression of proapoptotic genes have been investigated. Cytotoxic effects of Astragalus honey, ethanol extract of propolis and a sugar solution (as control) against HepG2, 5637 and L929 cell lines have been evaluated by the MTT assay. Total RNAs of treated cells were isolated and p53 and Bcl-2 gene expression were evaluated, using real-time PCR. Propolis IC50 values were 58, 30 and 15 μg/ml against L929, HepG2 and 5637, respectively. These values for honey were 3.1%, 2.4% and 1.9%, respectively. Propolis extract has increased the expression of the Bcl-2 gene in all cell lines whereas the honey decreased that significantly (P honey and propolis decreased p53 gene expression in HepG2 and 5637 significantly but not in L929 cells. The sugar solution increased the expression of p53 in two cancer cell lines but no significant changes were observed in the expression of this gene in L929 as normal mouse cell. By downregulation of Bcl-2 expression it could be concluded that the cytotoxicity of honey was more than two fold against tested cancer cells compared with the sugar solution. No significant changes were observed in the expression of p53 in honey-treated cells. Propolis had no significant effect on Bcl-2 and p53 gene expressions (P > 0.05).

  7. Study of chemical composition and characteristics of Centurea cyanus extract on colon cancer cell line and analysis of apoptosis gene expression

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    Amir Mirzaie

    2016-12-01

    Full Text Available Background: Centaurea cyanus is an endemic and well-known herbal medicine in Iran, is an annual flowering plant in the family of Asteraceae. The flowers are the part used in modern herbal medicine and are considered to have tonic, stimulant and emmenagogue properties, with action similar to that of blessed thistle. The aim this study was to investigate the phytochemical constituents of C. cyanus extract, its antioxidant, anti-tumor and anti-bacterial activities. Methods: This experimental study was conducted from June to January of 2015 in Islamic Azad University of Varamin, Iran. At first, the phytochemical components of C. cyanus extract was analyzed using gas chromatography–mass spectrometry (GC-MS method. Subsequently, the antibacterial potential of the extract was evaluated against 4 pathogenic bacteria including Staphylococcus aureus, Streptococcus pyogenes, Psedomonas aeroginosa and Klebsiella pnemoniae via minimum inhibitory concentration (MIC mathod. Moreover, the anti-oxidant and anti-tumor activities of extract on colon cancer cell line (HT29 were investigate using DPPH and MTT colorimetric methods, respectively. Finally, the Bax and Bcl2 apoptosis gene expression level was analyzed by quantitative Real-time PCR technique. Results: GC-MS analysis of C. cyanus extract was shown 19 major components and the most frequent component was belonged to n-Hexadecanoic acid (36.4% and Linoleic acid (19.3%. The maximum antibacterial activity of extract was observed on S. aureus and P. aeroginosa isolates. The antioxidant activity of the extract was 0.109±0.07 mg/ml. Moreover, the MTT results show that extract had IC50= 26.04±0.45 on HT29 cell line. The Real-time PCR results showed the expression level of Bax and Bcl2 was significantly increased and decreased respectively in colon cancer cell line (2.63±0.54 (P< 0.05, 0.38±0.72 (P< 0.05. Conclusion: The results of this study show that the extract had significant anti-bacterial and anti-cancer

  8. Antiproliferative Activity of the Methanolic Extract of Withania Somnifera Leaves from Faifa Mountains, Southwest Saudi Arabia, against Several Human Cancer Cell Lines.

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    Alfaifi, Mohammad Yahya; Saleh, Kamel Ahmed; El-Boushnak, Mohammed Atallah; Elbehairi, Serag Eldin I; Alshehri, Mohammed Ali; Shati, Ali Abdullah

    2016-01-01

    Cancer represent one of the most serious health problems and major causes of death around the world. Many anticancer drugs in clinical use today are natural products or derived from natural sources. Withania somnifera (L.) Dunal is a small shrub widely distributed in many parts of the world including Saudi Arabia. The antiproliferative activities of the methanolic extract of W. somnifera leaves collected from Faifa mountains, southwest Saudi Arabia against MCF-7, HCT116 and HepH2 cell lines were investigated. The extract showed a strong antiproliferative activity against all cell lines with IC50 values of 3.35, 2.19 and 1.89 μg/ml, respectively. Flow cytometry results showed that the extract arrested the cell cycle at S phase, and the increase in the caspase 3 activity suggested that the extract could induce cell apoptosis by a caspase mediated pathway. These results demonstrated that the methanolic extract of W. somnifera leaves collected from Faifa mountains has comparable strong antiproliferative activities to samples collected from different locations.

  9. Ethanol extract of Kilkyung-baeksan, a traditional herbal formula, induces G0/G1 cell cycle arrest in human lung cancer cell lines

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    Jinhee Kim

    2015-09-01

    Conclusion: EE-KKBS exerted its cytostatic activity through regulating G1 cell cycle checkpoint in lung cancer cells, and this activity is mainly mediated by one of its component herbs, seeds of Croton tiglium. Collectively, our data suggest that EE-KKBS could be a novel candidate for adjuvant therapy for lung cancer.

  10. A Preclinical Evaluation of Antrodia camphorata Alcohol Extracts in the Treatment of Non-Small Cell Lung Cancer Using Non-Invasive Molecular Imaging

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    Jeng-Feng Chiou

    2011-01-01

    Full Text Available This study was carried out to provide a platform for the pre-clinical evaluation of anti-cancer properties of a unique CAM (complementary and alternative medicine agent, Antrodia camphorata alcohol extract (ACAE, in a mouse model with the advantageous non-invasive in vivo bioluminescence molecular imaging technology. In vitro analyses on the proliferation, migration/invasion, cell cycle and apoptosis were performed on ACAE-treated non-small cell lung cancer cells, H441GL and control CGL1 cells. In vivo, immune-deficient mice were inoculated subcutaneously with H441GL followed by oral gavages of ACAE. The effect of ACAE on tumor progression was monitored by non-invasive bioluminescence imaging. The proliferation and migration/invasion of H441GL cells were inhibited by ACAE in a dose-dependent manner. In addition, ACAE induced cell cycle arrest at G0/G1 phase and apoptosis in H441GL cells as shown by flow cytometric analysis, Annexin-V immunoflourescence and DNA fragmentation. In vivo bioluminescence imaging revealed that tumorigenesis was significantly retarded by oral treatment of ACAE in a dose-dependent fashion. Based on our experimental data, ACAE contains anti-cancer properties and could be considered as a potential CAM agent in future clinical evaluation.

  11. First Evidence that Sika Deer (Cervus nippon) Velvet Antler Extract Suppresses Migration of Human Prostate Cancer Cells.

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    Tang, YuJiao; Jeon, Byong-Tae; Wang, Yanmei; Choi, Eun-Ju; Kim, Yon-Suk; Hwang, Jin-Woo; Park, Pyo-Jam; Moon, Sang Ho; Kim, Eun-Kyung

    2015-01-01

    Deer velvet antler (DVA) is one of the most popular medicines in China. Numerous studies have demonstrated that velvet antler possess biological effects. However, data regarding its anti-migration activity on prostate cancer is scarce. In this study, we investigated the inhibitory effect of top DVA (T-DVA) on the expression of prostate-specific antigen (PSA) and migration-related genes in the human prostate cancer cell, LNCaP. The T-DVA down-regulated the expression of PSA. In addition, the Radius(TM) assay revealed that T-DVA inhibited the migration behavior of prostate cancer cells. Furthermore, the expression of matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF) was also decreased with T-DVA. On the contrary, T-DVA increased the tissue inhibition of metalloproteinase (TIMP)-1 and (TIMP)-2. Taken together, our findings indicate that the T-DVA possesses anti-migration activity on prostate cancer cells. This is the first study of DVA to report the anti-migration activity on prostate cancer.

  12. Muscadine grape skin extract can antagonize Snail-cathepsin L-mediated invasion, migration and osteoclastogenesis in prostate and breast cancer cells.

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    Burton, Liza J; Smith, Basil A; Smith, Bethany N; Loyd, Quentin; Nagappan, Peri; McKeithen, Danielle; Wilder, Catera L; Platt, Manu O; Hudson, Tamaro; Odero-Marah, Valerie A

    2015-09-01

    To develop new and effective chemopreventive agents against bone metastasis, we assessed the effects of muscadine grape skin extract (MSKE), whose main bioactive component is anthocyanin, on bone turnover, using prostate and breast cancer cell models overexpressing Snail transcription factor. MSKE has been shown previously to promote apoptosis in prostate cancer cells without affecting normal prostate epithelial cells. Snail is overexpressed in prostate and breast cancer, and is associated with increased invasion, migration and bone turnover/osteoclastogenesis. Cathepsin L (CatL) is a cysteine cathepsin protease that is overexpressed in cancer and involved in bone turnover. Snail overexpression in prostate (LNCaP, ARCaP-E) and breast (MCF-7) cancer cells led to increased CatL expression/activity and phosphorylated STAT-3 (pSTAT-3), compared to Neo vector controls, while the reverse was observed in C4-2 (the aggressive subline of LNCaP) cells with Snail knockdown. Moreover, CatL expression was higher in prostate and breast tumor tissue compared to normal tissue. MSKE decreased Snail and pSTAT3 expression, and abrogated Snail-mediated CatL activity, migration and invasion. Additionally, Snail overexpression promoted osteoclastogenesis, which was significantly inhibited by the MSKE as effectively as Z-FY-CHO, a CatL-specific inhibitor, or osteoprotegerin, a receptor activator of nuclear factor kappa B ligand (RANKL) antagonist. Overall, these novel findings suggest that Snail regulation of CatL may occur via STAT-3 signaling and can be antagonized by MSKE, leading to decreased cell invasion, migration and bone turnover. Therefore, inhibition using a natural product such as MSKE could potentially be a promising bioactive compound for bone metastatic cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Ursolic Acid Inhibits Cigarette Smoke Extract-Induced Human Bronchial Epithelial Cell Injury and Prevents Development of Lung Cancer

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    Siming Yu

    2012-08-01

    Full Text Available Cigarette smoking is the main cause of chronic obstructive pulmonary disease and lung cancer. The present study was aimed to explore the chemopreventive effect of ursolic acid (UA on these diseases. In the CSE treated normal human bronchial epithelial cell model, UA alleviated cytotoxicity caused by CSE, recovered the intracellular redox balance, and relieved the stimulation of external deleterious factors as well. UA mitigated CSE-induced DNA damage through the Nrf2 (nuclear factor erythroid 2-related factor 2 pathway. Moreover, UA inhibited lung cancer development in the model established by A549 cells in nude mice in vivo. For the first time, our results indicate that UA could be developed as a potential lung cancer chemopreventive agent.

  14. Huaier aqueous extract inhibits ovarian cancer cell motility via the AKT/GSK3β/β-catenin pathway.

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    Xiaohui Yan

    Full Text Available Traditional Chinese medicine has gained popularity due to its ability to kill tumor cells. Recently, the apoptotic and anti-angiogenic effects of Trametes robiniophila murr (Huaier have been investigated. The aim of this study was to investigate its effect on cell mobility and tumor growth in ovarian cancer. Cell viability and motility were measured using SRB, scratch and migration assays. Cell apoptosis was analysed by annexin V/PI staining. Using a reverse-phase protein array (RPPA assay, we analyzed the levels of 153 proteins and/or phosphorylations in Huaier-treated and untreated cells. Huaier inhibited cell viability and induced both early and late apoptosis in SKOV3, SKOV3.ip1 and Hey cells in a time- and dose-dependent manner. Cell invasiveness and migration were also suppressed significantly. The RPPA results showed significant differences (of at least 30%; P <0.05 in the levels of 7 molecules in SKOV3 cells and 10 in SKOV3.ip1 cells between the untreated and treated cells. Most of the molecules identified play roles in cell proliferation, apoptosis or cell adhesion/invasion. Western blot analysis further validated that Huaier treatment resulted in decreased AKT phosphorylation, enhanced expression of total GSK3β, inhibition of the phosphorylation of GSK3β on S9, reduction of both cytoplasmic β-catenin expression and nuclear β-catenin translocation, and transcriptional repression of several Wnt/β-catenin target genes (DIXDC1, LRP6, WNT5A, and cyclin D1. After knocking down GSK3β, β-catenin expression could not be inhibited by Huaier. Finally, Huaier inhibited the growth of ovarian tumor xenografts in vivo. These studies indicate that Huaier inhibits tumor cell mobility in ovarian cancer via the AKT/GSK3β/β-catenin signaling pathway.

  15. Differential Control of Growth, Apoptotic Activity, and Gene Expression in Human Breast Cancer Cells by Extracts Derived from Medicinal Herbs Zingiber officinale

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    Ayman I. Elkady

    2012-01-01

    Full Text Available The present study aimed to examine the antiproliferative potentiality of an extract derived from the medicinal plant ginger (Zingiber officinale on growth of breast cancer cells. Ginger treatment suppressed the proliferation and colony formation in breast cancer cell lines, MCF-7 and MDA-MB-231. Meanwhile, it did not significantly affect viability of nontumorigenic normal mammary epithelial cell line (MCF-10A. Treatment of MCF-7 and MDA-MB-231 with ginger resulted in sequences of events marked by apoptosis, accompanied by loss of cell viability, chromatin condensation, DNA fragmentation, activation of caspase 3, and cleavage of poly(ADP-ribose polymerase. At the molecular level, the apoptotic cell death mediated by ginger could be attributed in part to upregulation of Bax and downregulation of Bcl-2 proteins. Ginger treatment downregulated expression of prosurvival genes, such as NF-κB, Bcl-X, Mcl-1, and Survivin, and cell cycle-regulating proteins, including cyclin D1 and cyclin-dependent kinase-4 (CDK-4. On the other hand, it increased expression of CDK inhibitor, p21. It also inhibited the expression of the two prominent molecular targets of cancer, c-Myc and the human telomerase reverse transcriptase (hTERT. These findings suggested that the ginger may be a promising candidate for the treatment of breast carcinomas.

  16. An investigation of compositions and effects of local herbal Glycyrrhiza glabra and Mentha pulegium extracts on Helicobacter pylori and cell Line of stomach cancer (AGS by MTT assays

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    Fereshteh Salmani Jamaat1

    2017-07-01

    Full Text Available Background & Aim:According to globally development of stomach cancer especially in Ardabil, Iran, as the second major cause of mortality throughout the world, increased drug-resistant bacteria including Helicobacter pylori as the most important risk factors for stomach cancer, and side effects of antibiotics and chemical drugs normally used to treat. Experimental: The current research was conducted to investigate the anticancer and antimicrobial effects of native herbs of liquorice (Glycyrrhiza glabra and pennyroyal (Mentha pulegium extractions for finding a solution with the lowest complications in control or treatment of stomach cancer.The extractions were firstly obtained using Soxhlet and methanol solvent and then their compounds were determined by GC/MS. Antimicrobial activity, MIC and MBC of the extractions were assessed respectively using agar diffusion and broth dilution test and the anticancer effect on stomach cancer (cell line AGS was assessed by MTT assay. H. pylori ATCC 26695 was respectively revived and purified on Brucella broth containing 7% citrated horse serum and Columbia agar. Results: The analysis showed that liquorice extract contains 15 compositions, mainly consists of 26.48% Nonane, 23.38% Ethylcyclohexan, 8.29% 3-Bromodecane, 10.31% trans-2-Heptenal, 8.93% 9-Octadecenamide and 4.68% β-pregna and pennyroyal extract contains 17 compositions, mainly including 3.36% Camphor, 22.79% Pulegone, 4.92% Paramenth-3-n8-l, 8.06% Menthoforan, 7.54% Cis-Isopulegon and 24.58% α-Selinene. The bacteria were resistant or semi-sensitive to common antibiotics, whereas had considerable sensitivity to herbal extracts and liquorice showed almost three times more antibacterial effect. Pennyroyal extract had no cytotoxic effects, but the anticancer effect was observed in liquorice extract with optimal concentration of 25 μg/ml after 48 hours. Recommended applications/industries: In conclusion, liquorice extract due to the significant health

  17. Water extract of Galla Rhois with steaming process enhances apoptotic cell death in human colon cancer cells

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    Nam-Hui Yim

    2016-12-01

    Conclusion: Compared with GRE, AGRE is more potent in its ability to induce apoptosis in HCT116 cells; therefore, we suggest that the steaming process may be useful as a feasible method for improving the anticancer effect of GRE.

  18. Cytotoxic activity of biosynthesized gold nanoparticles with an extract of the red seaweed Corallina officinalis on the MCF-7 human breast cancer cell line.

    Science.gov (United States)

    El-Kassas, Hala Yassin; El-Sheekh, Mostafa M

    2014-01-01

    Nano-biotechnology is recognized as offering revolutionary changes in the field of cancer therapy and biologically synthesized gold nanoparticles are known to have a wide range of medical applications. Gold nanoparticles (GNPs) were biosynthesized with an aqueous extract of the red alga Corallina officinalis, used as a reducing and stabilizing agent. GNPs were characterized using UV-Vis spectroscopy, transmission electron microscopy (TEM), energy dispersive analysis (EDX) and Fourier transform infra-red (FT-IR) spectroscopy and tested for cytotoxic activity against human breast cancer (MCF-7) cells cultured in Dulbecco's modified Eagle medium supplemented with 10% fetal bovine serum, considering their cytotoxicty and effects on cellular DNA. The biosynthesized GNPs were 14.6 ± 1 nm in diameter. FT-IR analysis showed that the hydroxyl functional group from polyphenols and carbonyl group from proteins could assist in formation and stabilization. The GNPs showed potent cytotoxic activity against MCF-7 cells, causing necrosis at high concentrations while lower concentrations were without effect as indicated by DNA fragmentation assay. The antitumor activity of the biosynthesized GNPs from the red alga Corallina officinalis against human breast cancer cells may be due to the cytotoxic effects of the gold nanoparticles and the polyphenolcontent of the algal extract.

  19. Potential Combinational Anti-Cancer Therapy in Non-Small Cell Lung Cancer with Traditional Chinese Medicine Sun-Bai-Pi Extract and Cisplatin.

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    Tseng, Chia-Yi; Lin, Chin-Hung; Wu, Lung-Yuan; Wang, Jhih-Syuan; Chung, Meng-Chi; Chang, Jing-Fen; Chao, Ming-Wei

    2016-01-01

    Traditional lung cancer treatments involve chemical or radiation therapies after surgical tumor removal; however, these procedures often kill normal cells as well. Recent studies indicate that chemotherapies, when combined with Traditional Chinese Medicines, may offer a new way to treat cancer. In vitro tests measuring the induction of autophagy and/or apoptosis were used to examine the cytotoxicity of SBPE, commonly used for lung inflammation on A549 cell line. The results indicated that intercellular levels of p62 and Atg12 were increased, LC3-I was cleaved into LC3-II, and autophagy was induced with SBPE only. After 24 hours, the apoptotic mechanism was induced. If the Cisplatin was added after cells reached the autophagy state, we observed synergistic effects of the two could achieve sufficient death of lung cancer cells. Therefore, the Cisplatin dosage used to induce apoptosis could be reduced by half, and the amount of time needed to achieve the inhibitory concentration of 50% was also half that of the original. In addition to inducing autophagy within a shortened period of time, the SBPE and chemotherapy drug combination therapy was able to achieve the objective of rapid low-dosage cancer cell elimination. Besides, SBPE was applied with Gemcitabine or Paclitaxel, and found that the combination treatment indeed achieve improved lung cancer cell killing effects. However, SBPE may also be less toxic to normal cells.

  20. Potential Combinational Anti-Cancer Therapy in Non-Small Cell Lung Cancer with Traditional Chinese Medicine Sun-Bai-Pi Extract and Cisplatin.

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    Chia-Yi Tseng

    Full Text Available Traditional lung cancer treatments involve chemical or radiation therapies after surgical tumor removal; however, these procedures often kill normal cells as well. Recent studies indicate that chemotherapies, when combined with Traditional Chinese Medicines, may offer a new way to treat cancer. In vitro tests measuring the induction of autophagy and/or apoptosis were used to examine the cytotoxicity of SBPE, commonly used for lung inflammation on A549 cell line. The results indicated that intercellular levels of p62 and Atg12 were increased, LC3-I was cleaved into LC3-II, and autophagy was induced with SBPE only. After 24 hours, the apoptotic mechanism was induced. If the Cisplatin was added after cells reached the autophagy state, we observed synergistic effects of the two could achieve sufficient death of lung cancer cells. Therefore, the Cisplatin dosage used to induce apoptosis could be reduced by half, and the amount of time needed to achieve the inhibitory concentration of 50% was also half that of the original. In addition to inducing autophagy within a shortened period of time, the SBPE and chemotherapy drug combination therapy was able to achieve the objective of rapid low-dosage cancer cell elimination. Besides, SBPE was applied with Gemcitabine or Paclitaxel, and found that the combination treatment indeed achieve improved lung cancer cell killing effects. However, SBPE may also be less toxic to normal cells.

  1. Green synthesis of NiO nanoparticles using Moringa oleifera extract and their biomedical applications: Cytotoxicity effect of nanoparticles against HT-29 cancer cells.

    Science.gov (United States)

    Ezhilarasi, A Angel; Vijaya, J Judith; Kaviyarasu, K; Maaza, M; Ayeshamariam, A; Kennedy, L John

    2016-11-01

    Green protocols for the synthesis of nickel oxide nanoparticles using Moringa oleifera plant extract has been reported in the present study as they are cost effective and ecofriendly, moreover this paper records that the nickel oxide (NiO) nanoparticles prepared from green method shows better cytotoxicity and antibacterial activity. The NiO nanoparticles were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), High resolution transmission electron microscopy (HRTEM), Energy dispersive X-ray analysis (EDX), and Photoluminescence spectroscopy (PL). The formation of a pure nickel oxide phase was confirmed by XRD and FTIR. The synthesized NiO nanoparticles was single crystalline having face centered cubic phase and has two intense photoluminescence emissions at 305.46nm and 410nm. The formation of nano- and micro-structures was confirmed by HRTEM. The in-vitro cytotoxicity and cell viability of human cancer cell HT-29 (Colon Carcinoma cell lines) and antibacterial studies against various bacterial strains were studied with various concentrations of nickel oxide nanoparticles prepared from Moringa oleifera plant extract. MTT assay measurements on cell viability and morphological studies proved that the synthesized NiO nanoparticles posses cytotoxic activity against human cancer cells and the various zones of inhibition (mm), obtained revealed the effective antibacterial activity of NiO nanoparticles against various Gram positive and Gram negative bacterial pathogens. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Effects of Biebersteinia multifida hydro-ethanol extract on proliferation and apoptosis of human prostate cancer and human embryonic kidney cells

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    Alireza Golshan

    2016-11-01

    Full Text Available Objective: Biebersteinia (Geraniaceae has a history of use in traditional medicine in some countries including Iran. In the present study, cytotoxic and apoptogenic properties of hydro-ethanol extract of B. multifidi was investigated on human prostate cancer cell lines (PC3 and DU 145 and human embryonic kidney 293 (HEK293 cells. Materials and Methods: Cells were cultured in RPMI-1640 medium supplemented with 10% FBS at 37ºC in a humidified atmosphere of 95% air and 5% CO2. The root of the plant was macerated with EtOH 70%. Cytotoxic activity of ethanol extract of B. multifida was assessed using alamarBlue® assay after 48 hr of treatment. Apoptotic cells were stained with propidium iodide (PI and detected by flow cytometry (sub-G1 peak. Results: B. multifidi had cytotoxic effect on malignant cells and normal HEK293 cells in a dose-dependent manner and significantly decreased the cell viability (IC50 values were between 199.2 and 302.9 µg/ml. B. multifida increased the sub-G1 peak in flow cytometry histogram of treated PC3 cells compared to control showing the induction of apoptosis and DNA fragmentation. Conclusion: Due to cytotoxic and apoptotic activity of B. multifida, the plant is suggested for further phytochemical analysis and mechanistic evaluation.

  3. Antiproliferative effect on human cancer cell lines after treatment with nimbolide extracted from an edible part of the neem tree (Azadirachta indica).

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    Roy, Molay Kumar; Kobori, Masuko; Takenaka, Makiko; Nakahara, Kazuhiko; Shinmoto, Hiroshi; Isobe, Seiichiro; Tsushida, Tojiro

    2007-03-01

    Nimbolide, a triterpenoid extracted from the flowers of the neem tree (Azadirachta indica), was found to have antiproliferative activity against some cancer cell lines. Treatment of cells with 0.5-5.0 microm concentrations of nimbolide resulted in moderate to very strong growth inhibition in U937, HL-60, THP1 and B16 cell lines. Flow cytometric analysis of U937 cells showed that nimbolide treatment (1-2.5 microm) resulted in cell cycle disruption by decreasing the number of cells in G0/G1 phase, with initial increases in S and G2/M phases. Cells exposed to a higher dose of nimbolide for a longer period displayed a severely damaged DNA profile, resulting in a remarkable increase in the number of cells in the sub-G1 fraction, with a reciprocal decrease of cells in all phases. Quantification of the expression of phosphatidylserine in the outer cell membrane showed that doses of nimbolide higher than 0.4 microm exerted remarkable lethality, with over 60% of cells exhibiting apoptotic features after exposure to 1.2 microm nimbolide. The antiproliferative effect of nimbolide and its apoptosis-inducing property raise hope for its use in anticancer therapy by enhancing the effectiveness of cell cycle disruption.

  4. Ganoderma tsugae Extract Inhibits Growth of HER2-Overexpressing Cancer Cells via Modulation of HER2/PI3K/Akt Signaling Pathway

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    Han-Peng Kuo

    2013-01-01

    Full Text Available Ganoderma, also known as Lingzhi or Reishi, has been used for medicinal purposes in Asian countries for centuries. It is a medicinal fungus with a variety of biological properties including immunomodulatory and antitumor activities. In this study, we investigated the molecular mechanisms by which Ganoderma tsugae (GT, one of the most common species of Ganoderma, inhibits the proliferation of HER2-overexpressing cancer cells. Here, we show that a quality assured extract of GT (GTE inhibited the growth of HER2-overexpressing cancer cells in vitro and in vivo and enhanced the growth-inhibitory effect of antitumor drugs (e.g., taxol and cisplatin in these cells. We also demonstrate that GTE induced cell cycle arrest by interfering with the HER2/PI3K/Akt signaling pathway. Furthermore, GTE curtailed the expression of the HER2 protein by modulating the transcriptional activity of the HER2 gene and the stability/degradation of the HER2 protein. In conclusion, this study suggests that GTE may be a useful adjuvant therapeutic agent in the treatment of cancer cells that highly express HER2.

  5. Anticancer activity of a sub-fraction of dichloromethane extract of Strobilanthes crispus on human breast and prostate cancer cells in vitro

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    Navaratnam Visweswaran

    2010-08-01

    Full Text Available Abstract Background The leaves of Strobilanthes crispus (S. crispus which is native to the regions of Madagascar to the Malay Archipelago, are used in folk medicine for their antidiabetic, diuretic, anticancer and blood pressure lowering properties. Crude extracts of this plant have been found to be cytotoxic to human cancer cell lines and protective against chemically-induced hepatocarcinogenesis in rats. In this study, the cytotoxicity of various sub-fractions of dichloromethane extract isolated from the leaves of S. crispus was determined and the anticancer activity of one of the bioactive sub-fractions, SC/D-F9, was further analysed in breast and prostate cancer cell lines. Methods The dichloromethane extract of S. crispus was chromatographed on silica gel by flash column chromatography. The ability of the various sub-fractions obtained to induce cell death of MCF-7, MDA-MB-231, PC-3 and DU-145 cell lines was determined using the LDH assay. The dose-response effect and the EC50 values of the active sub-fraction, SC/D-F9, were determined. Apoptosis was detected using Annexin V antibody and propidium iodide staining and analysed by fluorescence microscopy and flow cytometry, while caspase 3/7 activity was detected using FLICA caspase inhibitor and analysed by fluorescence microscopy. Results Selected sub-fractions of the dichloromethane extract induced death of MCF-7, MDA-MB-231, PC-3 and DU-145 cells. The sub-fraction SC/D-F9, consistently killed breast and prostate cancer cell lines with low EC50 values but is non-cytotoxic to the normal breast epithelial cell line, MCF-10A. SC/D-F9 displayed relatively higher cytotoxicity compared to tamoxifen, paclitaxel, docetaxel and doxorubicin. Cell death induced by SC/D-F9 occurred via apoptosis with the involvement of caspase 3 and/or 7. Conclusions A dichloromethane sub-fraction of S. crispus displayed potent anticancer activities in vitro that can be further exploited for the development of a

  6. Differential control of growth, apoptotic activity and gene expression in human colon cancer cells by extracts derived from medicinal herbs, Rhazya stricta and Zingiber officinale and their combination.

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    Elkady, Ayman I; Hussein, Rania Abd El Hamid; Abu-Zinadah, Osama A

    2014-11-07

    To investigate the effects of extracts from Rhazya stricta (R. stricta) and Zingiber officinale (Z. officinale) on human colorectal cancer cells. Human colorectal cancer cells (HCT116) were subjected to increasing doses of crude alkaloid extracts from R. stricta (CAERS) and crude flavonoid extracts from Z. officinale (CFEZO). Cells were then harvested after 24, 48 or 72 h and cell viability was examined by trypan blue exclusion dye test; clonogenicity and soft agar colony-forming assays were also carried out. Nuclear stain (Hoechst 33342), acridine orange/ethidium bromide double staining, agarose gel electrophoresis and comet assays were performed to assess pro-apoptotic potentiality of the extracts. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), using gene-specific primers and Western blot analyses were performed to assess the impact of CAERS and CFEZO on the expression levels of key regulatory proteins in HCT116 cells. Treatment with a combination of CAERS and CFEZO synergistically suppressed the proliferation, colony formation and anchorage-independent growth of HCT116 cells. Calculated IC50, after 24, 48 and 72 h, were 70, 90 and 130 μg/mL for CAERS, 65, 85 and 120 μg/mL for CFEZO and 20, 25 and 45 μg/mL for both agents, respectively. CAERS- and CFEZO-treated cells exhibited morphologic and biochemical features of apoptotic cell death. The induction of apoptosis was associated with the release of mitochondrial cytochrome c, an increase in the Bax/Bcl-2 ratio, activation of caspases 3 and 9 and cleavage of poly ADP-ribose polymerase. CAERS and CFEZO treatments downregulated expression levels of anti-apoptotic proteins including Bcl-2, Bcl-X, Mcl-1, survivin and XIAP, and upregulated expression levels of proapoptotic proteins such as Bad and Noxa. CAERS and CFEZO treatments elevated expression levels of the oncosuppressor proteins, p53, p21 and p27, and reduced levels of the oncoproteins, cyclin D1, cyclin/cyclin-dependent kinase-4 and

  7. Assessment of Cellular Responses to Oxidative Stress using MCF-7 Breast Cancer Cells, Black Seed (N. Sativa L. Extracts and H2O2

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    Ibrahim O. Farah

    2005-12-01

    Full Text Available Black seed (N. Sativa L is an oriental spice of the family Ranunculaceae that has long been rationally used as a natural medicine for treatment of many acute as well as chronic conditions including cardiovascular disease and immunological disorders. It has been used in the treatment of diabetes, hypertension, and dermatological conditions. There have been very few studies on the effects of N. Sativa as a chemoprevention of chronic diseases as well as in cancer prevention and/or therapy. Oxidative stress is a condition that underlies many acute as well as chronic conditions. The combination and role of oxidative stress and antioxidants in vivo is still a matter of conjecture. Our objective for the present study was to expose MCF-7 breast cancer cells in vitro (as a chronic disease example to aqueous and alcohol extracts and in combination with H2O2 as an oxidative stressor. Measurement of cell survival under various concentrations and mixtures was conducted using standard cell culture techniques, exposure protocols in 96 well plates and Fluorospectrosphotometry. Following cellular growth to 90% confluencey, exposure to water (WE and ethanol (AE extracts of N. sativa and H2O2 was performed. Cell survival indices were calculated from percent survival using regression analysis. Results showed that the alcohol extract and its mixtures were able to influence the survival of MCF-7 cells (indices ranged from 357.15- 809.50 Bg/ml in descending potency for H2O2+AE to the mix of 3. In contrast, H2O2 alone reduced effectively the survival of MCF-7 cells and the least effective combinations in descending potency were AE+H2O2, WE+H2O2, AE+WE, and WE+AE+H2O2. Mixtures other than AE+H2O2 showed possible interactions and loss of potency. In conclusion, N. Sativa alone or in combination with oxidative stress was found to be effective (in vitro in influencing the survival of MCF-7 breast cancer cells, unveiling promising opportunities in the field of cancer

  8. An in vitro based investigation of the cytotoxic effect of water extracts of the Chinese herbal remedy LD on cancer cells

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    Jones Lucy A

    2009-09-01

    Full Text Available Abstract Background Long Dan Xie Gan Wan (LD, a Chinese herbal remedy formulation, is traditionally used to treat a range of conditions, including gall bladder diseases, hepatitis, hyperthyroidism, migraines but it is not used for the management or treatment of cancer. However some of its herbal constituents, specifically Radix bupleuri, Radix scutellariae and Rhizoma alismatis have been shown to inhibit the growth of cancer cells. Thus, the aim of the study was to investigate the impact of LD on cancer cells in vitro. Methods HL60 and HT29 cancer cell lines were exposed to water extracts of LD (1:10, 1:50, 1:100 and/or 1:1000 prepared from a 3 mg/30 ml stock and for both cell lines growth, apoptotic induction, alterations in cell cycle characteristics and genotoxicity were investigated. The specificity of the action of LD on these cancer cell lines was also investigated by determining its effect on human peripheral blood lymphocytes. Preliminary chemical analysis was carried out to identify cytotoxic constituents of LD using HPLC and LCMS. Results LD was significantly cytotoxic to, and induced apoptosis in, both cell lines. Apoptotic induction appeared to be cell cycle independent at all concentrations of LD used (1:10, 1:50 and 1:100 for the HL60 cell lines and at 1:10 for the HT29 cell line. At 1:50 and 1:100 apoptotic induction by LD appeared to be cell cycle dependent. LD caused significant genotoxic damage to both cell lines compared to their respective controls. The specificity study showed that LD exerted a moderate cytotoxic action against non-proliferating and proliferating blood lymphocytes but not apoptosis. Chemical analysis showed that a number of fractions were found to exert a significant growth inhibitory effect. However, the molecular weights of compounds within these fractions did not correspond to those from the herbal constituents of LD. Conclusion It is possible that LD may have some chemotherapeutic potential. However

  9. Mitotic Arrest and Apoptosis in Breast Cancer Cells Induced by Origanum majorana Extract: Upregulation of TNF-α and Downregulation of Survivin and Mutant p53

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    Al Dhaheri, Yusra; Eid, Ali; AbuQamar, Synan; Attoub, Samir; Khasawneh, Mohammad; Aiche, Ghenima; Hisaindee, Soleiman; Iratni, Rabah

    2013-01-01

    Background In the present study, we investigated the effect of Origanum majorana ethanolic extract on the survival of the highly proliferative and invasive triple-negative p53 mutant breast cancer cell line MDA-MB-231. Results We found that O. majorana extract (OME) was able to inhibit the viability of the MDA-MB-231 cells in a time- and concentration-dependent manner. The effect of OME on cellular viability was further confirmed by the inhibition of colony growth. We showed, depending on the concentration used, that OME elicited different effects on the MDA-MB 231 cells. Concentrations of 150 and 300 µg/mL induced an accumulation of apoptotic–resistant population of cells arrested in mitotis and overexpressing the cyclin-dependent kinase inhibitor, p21 and the inhibitor of apoptosis, survivin. On the other hand, higher concentrations of OME (450 and 600 µg/mL) triggered a massive apoptosis through the extrinsic pathway, including the activation of tumor necrosis factor-α (TNF-α), caspase 8, caspase 3, and cleavage of PARP, downregulation of survivin as well as depletion of the mutant p53 in MDA-MB-231 cells. Furthermore, OME induced an upregulation of γ-H2AX, a marker of double strand DNA breaks and an overall histone H3 and H4 hyperacetylation. Conclusion Our findings provide strong evidence that O. majorana may be a promising chemopreventive and therapeutic candidate against cancer especially for highly invasive triple negative p53 mutant breast cancer; thus validating its complementary and alternative medicinal use. PMID:23451065

  10. Mitotic arrest and apoptosis in breast cancer cells induced by Origanum majorana extract: upregulation of TNF-α and downregulation of survivin and mutant p53.

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    Yusra Al Dhaheri

    Full Text Available BACKGROUND: In the present study, we investigated the effect of Origanum majorana ethanolic extract on the survival of the highly proliferative and invasive triple-negative p53 mutant breast cancer cell line MDA-MB-231. RESULTS: We found that O. majorana extract (OME was able to inhibit the viability of the MDA-MB-231 cells in a time- and concentration-dependent manner. The effect of OME on cellular viability was further confirmed by the inhibition of colony growth. We showed, depending on the concentration used, that OME elicited different effects on the MDA-MB 231 cells. Concentrations of 150 and 300 µg/mL induced an accumulation of apoptotic-resistant population of cells arrested in mitotis and overexpressing the cyclin-dependent kinase inhibitor, p21 and the inhibitor of apoptosis, survivin. On the other hand, higher concentrations of OME (450 and 600 µg/mL triggered a massive apoptosis through the extrinsic pathway, including the activation of tumor necrosis factor-α (TNF-α, caspase 8, caspase 3, and cleavage of PARP, downregulation of survivin as well as depletion of the mutant p53 in MDA-MB-231 cells. Furthermore, OME induced an upregulation of γ-H2AX, a marker of double strand DNA breaks and an overall histone H3 and H4 hyperacetylation. CONCLUSION: Our findings provide strong evidence that O. majorana may be a promising chemopreventive and therapeutic candidate against cancer especially for highly invasive triple negative p53 mutant breast cancer; thus validating its complementary and alternative medicinal use.

  11. A cytotoxic Petiveria alliacea dry extract induces ATP depletion and decreases β-F1-ATPase expression in breast cancer cells and promotes survival in tumor-bearing mice

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    John F. Hernández

    Full Text Available Abstract Metabolic plasticity in cancer cells assures cell survival and cell proliferation under variable levels of oxygen and nutrients. Therefore, new anticancer treatments endeavor to target such plasticity by modifying main metabolic pathways as glycolysis or oxidative phosphorylation. In American traditional medicine Petiveria alliacea L., Phytolaccacea, leaf extracts have been used for leukemia and breast cancer treatments. Herein, we study cytotoxicity and antitumoral effects of P. alliacea extract in tumor/non-tumorigenic cell lines and murine breast cancer model. Breast cancer cells treated with P. alliacea dry extract showed reduction in β-F1-ATPase expression, glycolytic flux triggering diminished intracellular ATP levels, mitochondrial basal respiration and oxygen consumption. Consequently, a decline in cell proliferation was observed in conventional and three-dimension spheres breast cancer cells culture. Additionally, in vivo treatment of BALB/c mice transplanted with the murine breast cancer TS/A tumor showed that P. alliacea extract via i.p. decreases the primary tumor growth and increases survival in the TS/A model.

  12. The aqueous extract of Ficus religiosa induces cell cycle arrest in human cervical cancer cell lines SiHa (HPV-16 Positive and apoptosis in HeLa (HPV-18 positive.

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    Amit S Choudhari

    Full Text Available Natural products are being extensively explored for their potential to prevent as well as treat cancer due to their ability to target multiple molecular pathways. Ficus religiosa has been shown to exert diverse biological activities including apoptosis in breast cancer cell lines. In the present study, we report the anti-neoplastic potential of aqueous extract of F. religiosa (FRaq bark in human cervical cancer cell lines, SiHa and HeLa. FRaq altered the growth kinetics of SiHa (HPV-16 positive and HeLa (HPV-18 positive cells in a dose-dependent manner. It blocked the cell cycle progression at G1/S phase in SiHa that was characterized by an increase in the expression of p53, p21 and pRb proteins with a simultaneous decrease in the expression of phospho Rb (ppRb protein. On the other hand, in HeLa, FRaq induced apoptosis through an increase in intracellular Ca(2+ leading to loss of mitochondrial membrane potential, release of cytochrome-c and increase in the expression of caspase-3. Moreover, FRaq reduced the migration as well as invasion capability of both the cervical cancer cell lines accompanied with downregulation of MMP-2 and Her-2 expression. Interestingly, FRaq reduced the expression of viral oncoproteins E6 and E7 in both the cervical cancer cell lines. All these data suggest that F. religiosa could be explored for its chemopreventive potential in cervical cancer.

  13. The antiproliferative activity of 3-deoxyanthocyanins extracted from red sorghum (Sorghum bicolor) bran through P(53)-dependent and Bcl-2 gene expression in breast cancer cell line.

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    Suganyadevi, P; Saravanakumar, K M; Mohandas, S

    2013-03-14

    The aim of this study was to investigate the anti proliferative activity of 3-deoxyanthocyanin extracted from red sorghum bran on human breast cancer cell line MCF 7. The confirmatory tests were carried out in vitro through the expression studies of p(53) and (bcl) 2 genes in MCF 7 cells. The 3-deoxyanthocyanins were isolated from red sorghum bran and cytotoxic studies were performed in MCF 7 cell line by MTT assay. The mRNA expression levels of p(53) and (bcl) 2 genes were performed using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis in MCF 7 cells. On cytotoxic studies, the present data indicates sorghum anthocyanins, which showed 84.09% of inhibition in the proliferation of MCF 7 cells, and the CTC(50) value was 300 μg/ml. The sorghum 3-deoxyanthocyanins induced apoptosis in MCF 7 was mediated by stimulation of the p(53) gene and down regulation of the (bcl) 2 gene. The significance of our work was the anthocyanin isolated from red sorghum bran inhibits the proliferation of human breast cancer cell line. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Effect of Helix aspersa extract on TNFα, NF-κB and some tumor suppressor genes in breast cancer cell line Hs578T.

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    El Ouar, Ibtissem; Braicu, Cornelia; Naimi, Dalila; Irimie, Alexendru; Berindan-Neagoe, Ioana

    2017-01-01

    The garden snail, Helix aspersa, is a big land snail widely found in the Mediterranean countries. It is one of the most consumed species and widely used in zootherapy. The present study was carried out to investigate for the first time the first time the antitumor activity of an aqueous extract from Helix aspersa. The effect of H. aspersa extract was studied on a triple negative breast cancer cell line Hs578T. Firstly, the morphological changes and the mode of cell death induced by the extract have been evaluated by microscopy and acridine orange/ethidium bromide staining. The effect of the extract at dilution 0.1% and 1% was then tested on some genes, regulators of cell death and proliferation like tumor necrosis factor α (TNFα), NF- κB, and the tumor suppressor genes P53 and PTEN. Data demonstrate that the extract induces necrosis in tumor cells. It enhances significantly the expression of TNFα; mRNA levels were 20 and 10 times more important in treated cells compared to nontreated cells. NF-κB and PTEN were inhibited with the dilution 1% after 8 and 24 hours of treatment. P53 expression was further inhibited but only with the highest dose, after 4, 8, and 24 hours. Our results show that H. aspersa extract has an antitumor activity against Hs578T cells; it is a potent stimulator for TNFα and a good inhibitor for NF-κB. Abbreviations used: AO: acridine orange; Bcl-2: B cell lymphoma 2. cDNA: complementary DNA; ELISA: enzyme linked immunosorbent assay; EB: ethidium bromide; IC50: the half maximal inhibitory concentration; mRNA: messenger RNA. MAPK: mitogen-activated protein kinase; NF-κB: nuclearfactorkappa B; PBS: phosphate buffered saline. PI3K: phospho-inositol 3 kinase; PTEN: phosphatase and tensin homolog; ROS: reactive oxygen species. RT-PCR: reverse transcription polymerase chain reaction; TNFα: tumor necrosis factor alpha. TNFR1: TNF receptor-1; TP53: tumor protein 53.

  15. Qualitative screening of phenolic compounds in olive leaf extracts by hyphenated liquid chromatography and preliminary evaluation of cytotoxic activity against human breast cancer cells.

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    Fu, Shaoping; Arráez-Roman, David; Segura-Carretero, Antonio; Menéndez, Javier A; Menéndez-Gutiérrez, María P; Micol, Vicente; Fernández-Gutiérrez, Alberto

    2010-05-01

    In this work, high-performance liquid chromatography (HPLC) coupled to electrospray time-of-flight mass spectrometry (ESI-TOF-MS) and electrospray ion trap multiple-stage tandem mass spectrometry (ESI-IT-MS(2)) has been applied to screen phenolic compounds in olive leaf extracts. The use of a small particle size C18 column (1.8 micro) provided great resolution and made separation of a lot of isomers possible. The structural characterization was based on accurate mass data obtained by ESI-TOF-MS, and the nature of fragmentation ions were further confirmed by ESI-IT-MS(2) when possible. In addition, we employed tetrazolium salt (MTT)-based assays to assess the effects of olive leaf extracts on the growth of human tumor-derived cells. Upon this approach, we achieved an accurate profile of olive leaf phenolics along with the identification of several important isomers of secoiridoids and flavonoids. This will allow a better understanding of the complete composition of olive-leaf-bioactive compounds as well as their involvement in Olea europaea L. biochemical pathways. Importantly, olive leaf extracts exhibited dose-dependent inhibitory effects on the metabolic status (cell viability) of three breast cancer models in vitro. Since the tumoricidal activity of the extracts should be mainly attributed to the identified olive leaf phenolics, these findings warrant further investigation at the structure-function molecular level to definitely establish the anticancer value of these phytochemicals.

  16. Anti-proliferative effect of an extract of the root of Polygonum multiflorum Thunb. on MCF-7 human breast cancer cells and the possible mechanisms.

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    Chen, Hong-Sheng; Liu, Yan; Lin, Luo-Qiang; Zhao, Jin-Lu; Zhang, Chun-Peng; Jin, Jun-Chao; Wang, Lei; Bai, Ming-Han; Wang, Yi-Chong; Liu, Ming; Shen, Bao-Zhong

    2011-01-01

    The root of Polygonum multiflorum Thunb. (PM) is utilized to treat many diseases associated with aging. Research also indicates that PM inhibits the proliferation of certain types of cancer cells. The aim of the present study was to evaluate the inhibitory effect of PM extract (PME) on the proliferation of MCF-7 cells and to investigate the underlying mechanisms. Inhibition of the proliferation of MCF-7 cells was determined by the MTT assay. Cell cycle distribution and apoptotic rates were evaluated by flow cytometry, and cell cycle and apoptosis-related protein expression was assessed by Western blotting. Apoptotic characteristics of MCF-7 cells were detected by transmission electron microscopy. The present study showed that PME at doses of 100, 150, 200 and 250 µg/ml significantly inhibited proliferation of MCF-7 cells in a time- and dose-dependent manner. Flow cytometry showed that the cell apoptotic rates were 9.1 ± 1.67 and 17.7 ± 2.93% after treatment with 100 and 200 µg/ml PME for 48 h, respectively. The proportions of cells in the G2/M phase were 37.9 ± 1.47 and 42.0 ± 1.71% after treatment with 100 and 200 µg/ml PME for 24 h, respectively. Western blot analysis showed that PME down-regulated the protein expression of Cdc25B and Cdc25C phosphatases accompanied by an increase in phospho-Cdk1, and PME promoted cytochrome c release from mitochondria into the cytosol to activate caspase-9. The present study demonstrated that PME inhibited MCF-7 cell proliferation by inducing cell cycle arrest in the G2/M phase and promoting cell apoptosis. The effects of PME on MCF-7 cells were associated with the modulation of the expression levels of proteins involved in the cell cycle and apoptosis. These data suggest that PME has promise as a treatment against breast cancer by inhibiting the proliferation of cancer cells.

  17. Biosynthesis, Antibacterial Activity and Anticancer Effects Against Prostate Cancer (PC-3) Cells of Silver Nanoparticles Using Dimocarpus Longan Lour. Peel Extract

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    He, Yan; Du, Zhiyun; Ma, Shijing; Cheng, Shupeng; Jiang, Sen; Liu, Yue; Li, Dongli; Huang, Huarong; Zhang, Kun; Zheng, Xi

    2016-06-01

    Metal nanoparticles, particularly silver nanoparticles (AgNPs), are developing more important roles as diagnostic and therapeutic agents for cancers with the improvement of eco-friendly synthesis methods. This study demonstrates the biosynthesis, antibacterial activity, and anticancer effects of silver nanoparticles using Dimocarpus Longan Lour. peel aqueous extract. The AgNPs were characterized by UV-vis absorption spectroscopy, X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), and Fourier transform infrared spectroscope (FTIR). The bactericidal properties of the synthesized AgNPs were observed via the agar dilution method and the growth inhibition test. The cytotoxicity effect was explored on human prostate cancer PC-3 cells in vitro by trypan blue assay. The expressions of phosphorylated stat 3, bcl-2, survivin, and caspase-3 were examined by Western blot analysis. The longan peel extract acted as a strong reducing and stabilizing agent during the synthesis. Water-soluble AgNPs of size 9-32 nm was gathered with a face-centered cubic structure. The AgNPs had potent bactericidal activities against gram-positive and gram-negative bacteria with a dose-related effect. AgNPs also showed dose-dependent cytotoxicity against PC-3 cells through a decrease of stat 3, bcl-2, and survivin, as well as an increase in caspase-3. These findings confirm the bactericidal properties and explored a potential anticancer application of AgNPs for prostate cancer therapy. Further research should be focused on the comprehensive study of molecular mechanism and in vivo effects on the prostate cancer.

  18. Effect of steviol, steviol glycosides and stevia extract on glucocorticoid receptor signaling in normal and cancer blood cells.

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    Panagiotou, Christina; Mihailidou, Chrysovalantou; Brauhli, George; Katsarou, Olga; Moutsatsou, Paraskevi

    2017-07-25

    The use of steviol glycosides as non-caloric sweeteners has proven to be beneficial for patients with type 2 diabetes mellitus (T2D), obesity, and metabolic syndrome. However, recent data demonstrate that steviol and stevioside might act as glucocorticoid receptor (GR) agonists and thus correlate with adverse effects on metabolism. Herein, we evaluated the impact of steviol, steviol glycosides, and a Greek-derived stevia extract on a number of key steps of GR signaling cascade in peripheral blood mononuclear cells (PBMCs) and in Jurkat leukemia cells. Our results revealed that none of the tested compounds altered the expression of primary GR-target genes (GILZ, FKPB5), GR protein levels or GR subcellular localization in PBMCs; those compounds increased GILZ and FKPB5 mRNA levels as well as GRE-mediated luciferase activity, inducing in parallel GR nuclear translocation in Jurkat cells. The GR-modulatory activity demonstrated by stevia-compounds in Jurkat cells but not in PBMCs may be due to a cell-type specific effect. Copyright © 2017. Published by Elsevier B.V.

  19. Antitumor Effects of Laminaria Extract Fucoxanthin on Lung Cancer

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    ChengHan Mei

    2017-02-01

    Full Text Available Lung cancer is the leading cause of cancer mortality worldwide and non-small-cell lung cancer (NSCLC is the most common type. Marine plants provide rich resources for anticancer drug discovery. Fucoxanthin (FX, a Laminaria japonica extract, has attracted great research interest for its antitumor activities. Accumulating evidence suggests anti-proliferative effects of FX on many cancer cell lines including NSCLCs, but the detailed mechanisms remain unclear. In the present investigation, we confirmed molecular mechanisms and in vivo anti-lung cancer effect of FX at the first time. Flow cytometry, real-time PCR, western blotting and immunohistochemistry revealed that FX arrested cell cycle and induced apoptosis by modulating expression of p53, p21, Fas, PUMA, Bcl-2 and caspase-3/8. These results show that FX is a potent marine drug for human non-small-cell lung cancer treatment.

  20. Screening of antiproliferative effect of aqueous extracts of plant foods consumed in México on the breast cancer cell line MCF-7.

    Science.gov (United States)

    García-Solís, Pablo; Yahia, Elhadi M; Morales-Tlalpan, Verónica; Díaz-Muñoz, Mauricio

    2009-01-01

    We evaluated the antiproliferative effect of aqueous extracts of 14 plant foods consumed in Mexico on the breast cancer cell line MCF-7. The plant foods used were avocado, black sapote, guava, mango, prickly pear cactus stems (called nopal in Mexico, cooked and raw), papaya, pineapple, four different cultivars of prickly pear fruit, grapes and tomato. β-Carotene, total phenolics and gallic acid contents and the antioxidant capacity, measured by the ferric reducing/antioxidant power and the 2,2-diphenyl-1,1-picrylhydrazyl radical scavenging assays, were analyzed in each aqueous extract. Only the papaya extract had a significant antiproliferative effect measured with the methylthiazolydiphenyl-tetrazolium bromide assay. We did not notice a relationship between the total phenolic content and the antioxidant capacity with antiproliferative effect. It is suggested that each extract of plant food has a unique combination of the quantity and quality of phytochemicals that could determine its biological activity. Besides, papaya represents a very interesting fruit to explore its antineoplastic activities.

  1. Lung cancer - small cell

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    ... carcinoma Small cell carcinoma Squamous cell carcinoma Secondhand smoke and lung cancer Normal lungs and alveoli Respiratory system Smoking hazards Bronchoscope References Horn L, Eisenberg R, ...

  2. Cell phones and cancer

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    Cancer and cell phones; Do cell phones cause cancer? ... Several major studies show no link between cell phones and cancer at this time. However, since the information available is based on short-term studies, the impact of many years of exposure ...

  3. Preparation of carotenoid extracts and nanoemulsions from Lycium barbarum L. and their effects on growth of HT-29 colon cancer cells

    Science.gov (United States)

    Hsu, H. J.; Huang, R. F.; Kao, T. H.; Inbaraj, B. S.; Chen, B. H.

    2017-03-01

    Lycium barbarum L., a traditional Chinese herb widely used in Asian countries, has been demonstrated to be protective against chronic diseases such as age-related macular degeneration. The objectives of this study were to determine the carotenoid content in L. barbarum by high-performance liquid chromatography-mass spectrometry, followed by preparation of a carotenoid nanoemulsion to evaluate the mechanism of inhibition on HT-29 colon cancer cells. The highest extraction yield of carotenoids was attained by employing a solvent system of hexane-ethanol-acetone (1:1:1, v/v/v). Nine carotenoids, including neoxanthin (4.47 μg g-1), all-trans-zeaxanthin and its cis-isomers (1666.3 μg g-1), all-trans-β-cryptoxanthin (51.69 μg g-1), all-trans-β-carotene and its cis-isomers (20.11 μg g-1), were separated within 45 min and quantified using a YMC C30 column and a gradient mobile phase of methanol-water (9:1, v/v) (A) and methylene chloride (B). A highly stable carotenoid nanoemulsion composed of CapryolTM 90, Transcutol®HP, Tween 80 and deionized water was prepared with a mean particle size of 15.1 nm. Characterization of zeaxanthin standard, blank nanoemulsion, carotenoid extract and carotenoid nanoemulsion by differential scanning calorimetry curves and Fourier transform infrared spectra revealed a good dispersion of zeaxanthin-dominated carotenoid extract with no significant chemical change after incorporation into nanoemulsion. The in vitro release kinetic study showed a higher release profile at pH 5.2 than at physiological pH 7.4, suggesting a rapid release of carotenoids in the acidic environment (pH 4.5-6.5) characteristic of tumors. Both the carotenoid nanoemulsion and the extract were effective at inhibiting growth of HT-29 colon cancer cells, with an IC50 of 4.5 and 4.9 μg ml-1, respectively. Also, both treatments could up-regulate p53 and p21 expression and down-regulate CDK2, CDK1, cyclin A and cyclin B expression and arrest the cell cycle at G2/M. The

  4. Extraction and separation of volatile and fixed oils from seeds of Myristica fragrans by supercritical CO₂: chemical composition and cytotoxic activity on Caco-2 cancer cells.

    Science.gov (United States)

    Piras, Alessandra; Rosa, Antonella; Marongiu, Bruno; Atzeri, Angela; Dessì, M Assunta; Falconieri, Danilo; Porcedda, Silvia

    2012-04-01

    Isolation of volatile and fixed oils from nutmeg have been obtained by supercritical fractioned extraction with carbon dioxide. Extraction experiments were carried out at pressures of 90 and 250 bar and temperature of 40 °C. The extraction step performed at 90 bar produced a volatile fraction mainly formed by myristicin (32.8%), sabinene (16.1%), α-pinene (9.8%), β-pinene (9.4%), β-phellandrene (4.9%), safrole (4.1%) and terpinen-4-ol (3.6%). The oil yield relative to this step of the process was 1.4% by weight of the charge. The last extraction step at 250 bar produced a butter-like material (nutmeg butter). The yield of this step was 14.4% by weight. The most represented fatty acids of fixed oil from nutmeg were 14:0 (79.2%), 18:1 n-9 (7.4%) and 16:0 (6.1%), and in particular the unsaturated fatty acids 18:1 n-9 averaged 32.96 μg/mg of oil. The level of myristicin in the nutmeg essential and fixed oils was also directly quantified by reversed HPLC-DAD. Moreover, the essential oil obtained from nutmeg, as well as myristicin, showed a significant in vitro inhibitory effect on the growth of a colon cancer cell line (undifferentiated Caco-2 cells). In this study, the chemical characterization and the anticancer activity of nutmeg oils obtained by supercritical extraction with carbon dioxide were investigated. This is important for their potential application in food and pharmaceutical industries. © 2012 Institute of Food Technologists®

  5. Anti-Cancer Properties of Diethylether Extract of Wood from Sukun ...

    African Journals Online (AJOL)

    Purpose: To evaluate the anti-cancer properties of the diethylether extract of Sukun (Artocarpus altilis) wood. Methods: The extract was tested in human T47D breast cancer cells and examined for its effect on cell viability, nuclear morphology and sub-G1 formation. Cell viability was determined by microculture tetrazolium ...

  6. Apoptosis-inducing factor and caspase-dependent apoptotic pathways triggered by different grape seed extracts on human colon cancer cell line Caco-2.

    Science.gov (United States)

    Dinicola, Simona; Cucina, Alessandra; Pasqualato, Alessia; Proietti, Sara; D'Anselmi, Fabrizio; Pasqua, Gabriella; Santamaria, Anna Rita; Coluccia, Pierpaolo; Laganà, Aldo; Antonacci, Donato; Giuliani, Alessandro; Bizzarri, Mariano

    2010-09-01

    Consumption of grape seed extract (GSE) is widely marketed as a dietary supplement and is considered safe for human health. Nevertheless, the analytical composition of GSE from different grape cultivars, growing in special agronomic constraints, differs greatly in flavan-3-ols content. The major concern with GSE studies is a lack of availability of uniformly standardised preparations, which raises an important question whether different GSE samples have comparable activity and trigger the same mechanisms of action on a given biological system. Therefore, it is tempting to speculate that GSE, obtained from different cultivars, could exert differentiated anticancer effects. The focus of the present study is to determine the selective biological efficacy of GSE obtained from three different sources on the human colon cancer cell line Caco-2. Irrespective of its source, high doses of GSE induced a significant inhibition on Caco-2 cell growth. Moreover, apoptosis was enhanced through both caspase-dependent and caspase-independent mechanisms, leading to an early apoptosis-inducing factor release and, further, to a dramatic increase in caspase 7 and 3 activity. However, a significant difference in apoptotic rates induced by the three grape sources clearly emerged when treating cancer cells with low and intermediate GSE concentrations (25 and 50 microg/ml).

  7. Comparative Study of Green Sub- and Supercritical Processes to Obtain Carnosic Acid and Carnosol-Enriched Rosemary Extracts with in Vitro Anti-Proliferative Activity on Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Andrea del Pilar Sánchez-Camargo

    2016-12-01

    Full Text Available In the present work, four green processes have been compared to evaluate their potential to obtain rosemary extracts with in vitro anti-proliferative activity against two colon cancer cell lines (HT-29 and HCT116. The processes, carried out under optimal conditions, were: (1 pressurized liquid extraction (PLE, using an hydroalcoholic mixture as solvent at lab-scale; (2 Single-step supercritical fluid extraction (SFE at pilot scale; (3 Intensified two-step sequential SFE at pilot scale; (4 Integrated PLE plus supercritical antisolvent fractionation (SAF at pilot scale. Although higher extraction yields were achieved by using PLE (38.46% dry weight, this extract provided the lowest anti-proliferative activity with no observed cytotoxic effects at the assayed concentrations. On the other hand, extracts obtained using the PLE + SAF process provided the most active rosemary extracts against both colon cancer cell lines, with LC50 ranging from 11.2 to 12.4 µg/mL and from 21.8 to 31.9 µg/mL for HCT116 and HT-29, respectively. In general, active rosemary extracts were characterized by containing carnosic acid (CA and carnosol (CS at concentrations above 263.7 and 33.9 mg/g extract, respectively. Some distinct compounds have been identified in the SAF extracts (rosmaridiphenol and safficinolide, suggesting their possible role as additional contributors to the observed strong anti-proliferative activity of CA and CS in SAF extracts.

  8. Gastrin releasing peptide GRP(14-27) in human breast cancer cells and in small cell lung cancer

    DEFF Research Database (Denmark)

    Vangsted, A J; Andersen, E V; Nedergaard, L

    1991-01-01

    Immunoreactivity related to the gastrin-releasing peptide (GRP) precursor was detected in four different human breast cancer cell lines. The amounts and the characteristics in extracts from different breast carcinoma cells were compared with cell extracts from small cell lung cancer (SCLC) cells...

  9. Mechanism of modulation through PI3K-AKT pathway about Nepeta cataria L.'s extract in non-small cell lung cancer.

    Science.gov (United States)

    Fan, Jiaxin; Bao, Yongrui; Meng, Xiansheng; Wang, Shuai; Li, Tianjiao; Chang, Xin; Yang, Guanlin; Bo, Tao

    2017-05-09

    Non-small cell lung cancer (NSCLC) is regarded as one of the major intractable diseases, which was cured mainly by chemotherapeutics in the clinical treatment at present. But it is still a vital mission for the current medical and researchers that hunting a natural medicine which have little side effects and high-efficiency against the NSCLC on account of the shortcomings on current drugs. Nepeta cataria L. plays an important role in anti-cancer treatment according to the reports which was recorded in the Chinese Pharmacopoeia of version 2015 and belongs to one of the Traditional Chinese medicine (TCM). Microfluidic chip technology is widely used in scientific research field due to its high-throughput, high sensitivity and low cost with the continuous progress of science and technology. In this study, we investigate the effect of total flavonoid extracted from Nepeta cataria L. (TFS) through human lung cancer cell line A549 based on the microfluidic device and Flow Cytometry. So we detected the mRNA expression of MicroRNA-126 (miR-126), VEGF, PI3K, PTEN and proteins expression respectively to explore the partial PI3K-AKT pathway molecular mechanisms through Quantitative Real-time PCR (qRT-PCR) and Western Blot. The results showed that TFS can disturb the expression of miR-126 and regulate the PI3K-AKT signaling pathway to meet the effect of anti-cancer. Taking all these results into consideration we can draw a conclusion that TFS may be used as a novel therapeutic agent for NSCLC in the near future.

  10. Mechanism of modulation through PI3K-AKT pathway about Nepeta cataria L.’s extract in non-small cell lung cancer

    Science.gov (United States)

    Meng, Xiansheng; Wang, Shuai; Li, Tianjiao; Chang, Xin; Yang, Guanlin; Bo, Tao

    2017-01-01

    Non-small cell lung cancer (NSCLC) is regarded as one of the major intractable diseases, which was cured mainly by chemotherapeutics in the clinical treatment at present. But it is still a vital mission for the current medical and researchers that hunting a natural medicine which have little side effects and high-efficiency against the NSCLC on account of the shortcomings on current drugs. Nepeta cataria L. plays an important role in anti-cancer treatment according to the reports which was recorded in the Chinese Pharmacopoeia of version 2015 and belongs to one of the Traditional Chinese medicine (TCM). Microfluidic chip technology is widely used in scientific research field due to its high-throughput, high sensitivity and low cost with the continuous progress of science and technology. In this study, we investigate the effect of total flavonoid extracted from Nepeta cataria L. (TFS) through human lung cancer cell line A549 based on the microfluidic device and Flow Cytometry. So we detected the mRNA expression of MicroRNA-126 (miR-126), VEGF, PI3K, PTEN and proteins expression respectively to explore the partial PI3K-AKT pathway molecular mechanisms through Quantitative Real-time PCR (qRT-PCR) and Western Blot. The results showed that TFS can disturb the expression of miR-126 and regulate the PI3K-AKT signaling pathway to meet the effect of anti-cancer. Taking all these results into consideration we can draw a conclusion that TFS may be used as a novel therapeutic agent for NSCLC in the near future. PMID:28404902

  11. Preparation of catechin extracts and nanoemulsions from green tea leaf waste and their inhibition effect on prostate cancer cell PC-3

    Science.gov (United States)

    Tsai, Yin-Jieh; Chen, Bing-Huei

    2016-01-01

    Green tea is one of the most commonly consumed natural health beverages in Taiwan’s market, with the major functional component catechin being shown to possess several biological activities such as antioxidation, anticancer, and prevention of cardiovascular disease. The objectives of this study were to develop a high-performance liquid chromatography–mass spectrometry method to determine the variety and content of catechins in green tea leaf waste, a by-product obtained during processing of tea beverage. In addition, catechin nanoemulsion was prepared to study its inhibition effect on prostate cancer cell PC-3. Results showed that a total of eight catechin standards were separated within 25 minutes by using a Gemini C18 column and a gradient mobile phase of 0.1% formic acid (A) and acetonitrile (B) with flow rate at 1 mL/min, column temperature at 30°C, and detection wavelength at 280 nm. Among various extraction solvents, 50% ethanol generated the highest yield of total catechins from tea leaf waste, of which five catechins were identified and quantified. The catechin nanoemulsion was composed of catechin extract, lecithin, Tween 80, and deionized water in an appropriate proportion, with the mean particle size being 11.45 nm, encapsulation efficiency 88.1%, and zeta potential −66.3 mV. A high stability of catechin nanoemulsion was shown over a storage period of 120 days at 4°C. Both catechin extract and nanoemulsion could inhibit growth of PC-3 tumor cells, with the half maximal inhibitory concentration being 15.4 μg/mL and 8.5 μg/mL, respectively. The PC-3 cell cycle was arrested at S phase through elevation of P27 expression and decline of cyclin A, cyclin B, cyclin-dependent kinase 2, and cyclin-dependent kinase 1 expression. In addition, both catechin extract and nanoemulsion could induce apoptosis of PC-3 cells through decrease in B-cell lymphoma 2 (bcl-2) expression and increase in cytochrome c expression for activation of caspase-3, caspase-8, and

  12. Preparation of catechin extracts and nanoemulsions from green tea leaf waste and their inhibition effect on prostate cancer cell PC-3.

    Science.gov (United States)

    Tsai, Yin-Jieh; Chen, Bing-Huei

    2016-01-01

    Green tea is one of the most commonly consumed natural health beverages in Taiwan's market, with the major functional component catechin being shown to possess several biological activities such as antioxidation, anticancer, and prevention of cardiovascular disease. The objectives of this study were to develop a high-performance liquid chromatography-mass spectrometry method to determine the variety and content of catechins in green tea leaf waste, a by-product obtained during processing of tea beverage. In addition, catechin nanoemulsion was prepared to study its inhibition effect on prostate cancer cell PC-3. Results showed that a total of eight catechin standards were separated within 25 minutes by using a Gemini C18 column and a gradient mobile phase of 0.1% formic acid (A) and acetonitrile (B) with flow rate at 1 mL/min, column temperature at 30°C, and detection wavelength at 280 nm. Among various extraction solvents, 50% ethanol generated the highest yield of total catechins from tea leaf waste, of which five catechins were identified and quantified. The catechin nanoemulsion was composed of catechin extract, lecithin, Tween 80, and deionized water in an appropriate proportion, with the mean particle size being 11.45 nm, encapsulation efficiency 88.1%, and zeta potential -66.3 mV. A high stability of catechin nanoemulsion was shown over a storage period of 120 days at 4°C. Both catechin extract and nanoemulsion could inhibit growth of PC-3 tumor cells, with the half maximal inhibitory concentration being 15.4 μg/mL and 8.5 μg/mL, respectively. The PC-3 cell cycle was arrested at S phase through elevation of P27 expression and decline of cyclin A, cyclin B, cyclin-dependent kinase 2, and cyclin-dependent kinase 1 expression. In addition, both catechin extract and nanoemulsion could induce apoptosis of PC-3 cells through decrease in B-cell lymphoma 2 (bcl-2) expression and increase in cytochrome c expression for activation of caspase-3, caspase-8, and

  13. Potential cancer-chemopreventive activities of wine stilbenoids and flavans extracted from grape (Vitis vinifera) cell cultures.

    Science.gov (United States)

    Waffo-Téguo, P; Hawthorne, M E; Cuendet, M; Mérillon, J M; Kinghorn, A D; Pezzuto, J M; Mehta, R G

    2001-01-01

    Moderate consumption of wine is associated with a reduced risk of cancer. Grape plant cell cultures were used to purify 12 phenols: the stilbenoids trans-astringin, trans-piceid (2), trans-resveratroloside, trans-resveratrol, trans-piceatannol, cis-resveratroloside, cis-piceid, and cis-resveratrol; the flavans (+)-catechin, (-)-epicatechin, and epicatechin 3-O-gallate; and the flavan dimer procyanidin B2 3'-O-gallate. These compounds were evaluated for potential to inhibit cyclooxygenases and preneoplastic lesion formation in carcinogen-treated mouse mammary glands in organ culture. At 10 micrograms/ml, trans-astringin and trans-piceatannol inhibited development of 7,12-dimethylbenz[a]anthracene-induced preneoplastic lesions in mouse mammary glands with 68.8% and 76.9% inhibition, respectively, compared with untreated glands. The latter compound was the most potent of the 12 compounds tested in this assay, with the exception of trans-resveratrol (87.5% inhibition). In the cyclooxygenase (COX)-1 assay, trans isomers of the stilbenoids appear to be more active than cis isomers: trans-resveratrol [50% inhibitory concentration (IC50) = 14.9 microM, 96%] vs. cis-resveratrol (IC50 = 55.4 microM). In the COX-2 assay, among the compounds tested, only trans- and cis-resveratrol exhibited significant inhibitory activity (IC50 = 32.2 and 50.2 microM, respectively). This is the first report showing the potential cancer-chemopreventive activity of trans-astringin, a plant stilbenoid recently found in wine. trans-Astringin and its aglycone trans-piceatannol were active in the mouse mammary gland organ culture assay but did not exhibit activity in COX-1 and COX-2 assays. trans-Resveratrol was active in all three of the bioassays used in this investigation. These findings suggest that trans-astringin and trans-piceatannol may function as potential cancer-chemopreventive agents by a mechanism different from that of trans-resveratrol.

  14. Effects of Phytoestrogen Extracts Isolated from Elder Flower on Hormone Production and Receptor Expression of Trophoblast Tumor Cells JEG-3 and BeWo, as well as MCF7 Breast Cancer Cells.

    Science.gov (United States)

    Schröder, Lennard; Richter, Dagmar Ulrike; Piechulla, Birgit; Chrobak, Mareike; Kuhn, Christina; Schulze, Sandra; Abarzua, Sybille; Jeschke, Udo; Weissenbacher, Tobias

    2016-10-08

    Hereinwe investigated the effect of elderflower extracts (EFE) and of enterolactone/enterodiol on hormone production and proliferation of trophoblast tumor cell lines JEG-3 and BeWo, as well as MCF7 breast cancer cells. The EFE was analyzed by mass spectrometry. Cells were incubated with various concentrations of EFE. Untreated cells served as controls. Supernatants were tested for estradiol production with an ELISA method. Furthermore, the effect of the EFE on ER/ER/PR expression was assessed by immunocytochemistry. EFE contains a substantial amount of lignans. Estradiol production was inhibited in all cells in a concentration-dependent manner. EFE upregulated ER in JEG-3 cell lines. In MCF7 cells, a significant ER downregulation and PR upregulation were observed. The control substances enterolactone and enterodiol in contrast inhibited the expression of both ER and of PR in MCF7 cells. In addition, the production of estradiol was upregulated in BeWo and MCF7 cells in a concentration dependent manner. The downregulating effect of EFE on ER expression and the upregulation of the PR expression in MFC-7 cells are promising results. Therefore, additional unknown substances might be responsible for ER downregulation and PR upregulation. These findings suggest potential use of EFE in breast cancer prevention and/or treatment and warrant further investigation.

  15. Effects of Phytoestrogen Extracts Isolated from Elder Flower on Hormone Production and Receptor Expression of Trophoblast Tumor Cells JEG-3 and BeWo, as well as MCF7 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Lennard Schröder

    2016-10-01

    Full Text Available Hereinwe investigated the effect of elderflower extracts (EFE and of enterolactone/enterodiol on hormone production and proliferation of trophoblast tumor cell lines JEG-3 and BeWo, as well as MCF7 breast cancer cells. The EFE was analyzed by mass spectrometry. Cells were incubated with various concentrations of EFE. Untreated cells served as controls. Supernatants were tested for estradiol production with an ELISA method. Furthermore, the effect of the EFE on ERα/ERβ/PR expression was assessed by immunocytochemistry. EFE contains a substantial amount of lignans. Estradiol production was inhibited in all cells in a concentration-dependent manner. EFE upregulated ERα in JEG-3 cell lines. In MCF7 cells, a significant ERα downregulation and PR upregulation were observed. The control substances enterolactone and enterodiol in contrast inhibited the expression of both ER and of PR in MCF7 cells. In addition, the production of estradiol was upregulated in BeWo and MCF7 cells in a concentration dependent manner. The downregulating effect of EFE on ERα expression and the upregulation of the PR expression in MFC-7 cells are promising results. Therefore, additional unknown substances might be responsible for ERα downregulation and PR upregulation. These findings suggest potential use of EFE in breast cancer prevention and/or treatment and warrant further investigation.

  16. Schizandra chinensis extracts induce apoptosis in human gastric cancer cells via JNK/p38 MAPK activation and the ROS-mediated/mitochondria-dependent pathway.

    Science.gov (United States)

    Kim, Hyun Sul; Lee, Jae Hwa; Park, Hyun Soo; Lee, Geum San; Kim, Hyung Woo; Ha, Ki-Tae; Kim, Byung Joo

    2015-02-01

    Schizandra chinensis Baill (Magnoliaceae) fruit extract (SCE) is considered a traditional herbal medicine for the treatment and alleviation of various diseases. Gastric cancer is the second most common cause of cancer-related death worldwide, and the first most common in Korea. This study investigates the mechanism of SCE-induced apoptosis in AGS human gastric cancer cells. SCE concentrations from 100 to 400 µg/ml were used. Cell viabilities were determined using MTT assay. Members of the Bcl-2 family and Bax were detected by Western blotting. RT-PCR was performed to measure the expression level of the Fas/FasL pro-apoptotic genes. SCE inhibited the proliferation AGS cells for 24 or 72 h (inhibition by 3.1% ± 5.2% at 100 µg/ml and 87.3% ± 7.6% at 400 µg/ml at 24 h and by 40.2% ± 5.3% 100 µg/ml and 95.3% ± 1.3% 400 µg/ml at 72 h) and increased the sub-G1 phase (25.3% ± 5.2% at 100 µg/ml and 370.2% ± 7.2% at 400 µg/ml) and the mitochondrial membrane depolarization (11.2% ± 2.1% at 100 µg/ml and 311.5% ± 6.1% at 400 µg/ml). The SCE-induced apoptotic cell death showed the down-regulation of Bcl-2, but up-regulation of Bax. Subsequently, SCE increased the expression level of Fas/FasL, activated caspase-9 and -3, and increased reactive oxygen species generation. Also, JNK II inhibitor or a p38 MAPK inhibitor inhibited SCE-induced cell death. These results indicate that SCE might be an effective chemotherapeutic for the treatment of human gastric cancer.

  17. Gene expression profiles of different breast cancer cells compared with their responsiveness to fermented mistletoe (Viscum album L.) extracts Iscador from oak (Quercus), pine (Pinus), white fir (Abies) and apple tree (Malus) in vitro.

    Science.gov (United States)

    Eggenschwiler, Jenny; Patrignani, Andrea; Wagner, Ulrich; Rehrauer, Hubert; Schlapbach, Ralph; Rist, Lukas; Ramos, Mac H; Viviani, Angelika

    2006-06-01

    Cytotoxicity assays in vitro (MTT test) showed that the different breast cancer cell lines Kpl-1, MCF-7 and Mfm-223 respond differently to the mistletoe (Viscum album L.) preparations Iscador. Quercus (Qu), Abies (A), Malus (M) and Pinus (P). In order to determine the differences in the responsiveness of the cells more exactly, the gene expression profiles were determined by cells, which were treated with Mistletoe extracts, compared with untreated control cells. Such differences can be analysed in more detail by looking at the gene expression using Human Whole Genome microarray chips (41,000 genes). The results of the transcriptome analyses suggested that Iscador preparations influenced the overregulation of genes regarding immune defense, stress response, apoptosis and cell-cell adhesion pathways. Within the Mfm-223-Zellen was the Genexpression in MCF-7 and Kpl-1. The MCF-7 cells were affected on the genes which are involved in cell-cell contacts whereas Kpl-1 responded to the mistletoe extracts by changing the mRNA levels of the immune and stress response pathways. Concerning the effects of the mistletoe extract, we conclude that Iscador Qu and M have a greater influence on the immune defense and stress response genes whereas Iscador A tends to affect the cell-cell adhesion and cytoskeleton pathways. In summary, cDNA microarray analyses give us information on whether a cancer cell is sensitive to mistletoe extracts in relation to how many genes are significantly overrepresented after mistletoe treatment, and whether a particular mistletoe extract is more effective on a specific cancer cell than the other preparation.

  18. Hibiscus sabdariffa Leaf Extract Inhibits Human Prostate Cancer Cell Invasion via Down-Regulation of Akt/NF-κB/MMP-9 Pathway

    Science.gov (United States)

    Chiu, Chun-Tang; Chen, Jing-Hsien; Chou, Fen-Pi; Lin, Hui-Hsuan

    2015-01-01

    Hibiscus sabdariffa leaf has been previously shown to possess hypoglycemic, hypolipidemic, and antioxidant effects, and induce tumor cell apoptosis. However, the molecular mechanisms involved in the anticancer activity of H. sabdariffa leaf extract (HLE) are poorly understood. The object of the study was to examine the anti-invasive potential of HLE. First, HLE was demonstrated to be rich in polyphenols. The results of wound-healing assay and in vitro transwell assay revealed that HLE dose-dependently inhibited the migration and invasion of human prostate cancer LNCaP (lymph node carcinoma of the prostate) cells under non-cytotoxic concentrations. Our results further showed that HLE exerted an inhibitory effect on the activity and expressions of matrix metalloproteinase-9 (MMP-9). The HLE-inhibited MMP-9 expression appeared to be a consequence of nuclear factor-kappaB (NF-κB) inactivation because its DNA-binding activity was suppressed by HLE. Molecular data showed all these influences of HLE might be mediated via inhibition of protein kinase B (PKB, also known as Akt)/NF-κB/MMP-9 cascade pathway, as demonstrated by the transfection of Akt1 overexpression vector. Finally, the inhibitory effect of HLE was proven by its inhibition on the growth of LNCaP cells and the expressions of metastasis-related molecular proteins in vivo. These findings suggested that the inhibition of MMP-9 expression by HLE may act through the suppression of the Akt/NF-κB signaling pathway, which in turn led to the reduced invasiveness of the cancer cells. PMID:26115086

  19. Hibiscus sabdariffa Leaf Extract Inhibits Human Prostate Cancer Cell Invasion via Down-Regulation of Akt/NF-kB/MMP-9 Pathway.

    Science.gov (United States)

    Chiu, Chun-Tang; Chen, Jing-Hsien; Chou, Fen-Pi; Lin, Hui-Hsuan

    2015-06-24

    Hibiscus sabdariffa leaf has been previously shown to possess hypoglycemic, hypolipidemic, and antioxidant effects, and induce tumor cell apoptosis. However, the molecular mechanisms involved in the anticancer activity of H. sabdariffa leaf extract (HLE) are poorly understood. The object of the study was to examine the anti-invasive potential of HLE. First, HLE was demonstrated to be rich in polyphenols. The results of wound-healing assay and in vitro transwell assay revealed that HLE dose-dependently inhibited the migration and invasion of human prostate cancer LNCaP (lymph node carcinoma of the prostate) cells under non-cytotoxic concentrations. Our results further showed that HLE exerted an inhibitory effect on the activity and expressions of matrix metalloproteinase-9 (MMP-9). The HLE-inhibited MMP-9 expression appeared to be a consequence of nuclear factor-kappaB (NF-κB) inactivation because its DNA-binding activity was suppressed by HLE. Molecular data showed all these influences of HLE might be mediated via inhibition of protein kinase B (PKB, also known as Akt)/NF-kB/MMP-9 cascade pathway, as demonstrated by the transfection of Akt1 overexpression vector. Finally, the inhibitory effect of HLE was proven by its inhibition on the growth of LNCaP cells and the expressions of metastasis-related molecular proteins in vivo. These findings suggested that the inhibition of MMP-9 expression by HLE may act through the suppression of the Akt/NF-kB signaling pathway, which in turn led to the reduced invasiveness of the cancer cells.

  20. Muscadine Grape Skin Extract Induces an Unfolded Protein Response-Mediated Autophagy in Prostate Cancer Cells: A TMT-Based Quantitative Proteomic Analysis.

    Science.gov (United States)

    Burton, Liza J; Rivera, Mariela; Hawsawi, Ohuod; Zou, Jin; Hudson, Tamaro; Wang, Guangdi; Zhang, Qiang; Cubano, Luis; Boukli, Nawal; Odero-Marah, Valerie

    2016-01-01

    Muscadine grape skin extract (MSKE) is derived from muscadine grape (Vitis rotundifolia), a common red grape used to produce red wine. Endoplasmic reticulum (ER) stress activates the unfolded protein response (UPR) that serves as a survival mechanism to relieve ER stress and restore ER homeostasis. However, when persistent, ER stress can alter the cytoprotective functions of the UPR to promote autophagy and cell death. Although MSKE has been documented to induce apoptosis, it has not been linked to ER stress/UPR/autophagy. We hypothesized that MSKE may induce a severe ER stress response-mediated autophagy leading to apoptosis. As a model, we treated C4-2 prostate cancer cells with MSKE and performed a quantitative Tandem Mass Tag Isobaric Labeling proteomic analysis. ER stress response, autophagy and apoptosis were analyzed by western blot, acridine orange and TUNEL/Annexin V staining, respectively. Quantitative proteomics analysis indicated that ER stress response proteins, such as GRP78 were greatly elevated following treatment with MSKE. The up-regulation of pro-apoptotic markers PARP, caspase-12, cleaved caspase-3, -7, BAX and down-regulation of anti-apoptotic marker BCL2 was confirmed by Western blot analysis and apoptosis was visualized by increased TUNEL/Annexin V staining upon MSKE treatment. Moreover, increased acridine orange, and LC3B staining was detected in MSKE-treated cells, suggesting an ER stress/autophagy response. Finally, MSKE-mediated autophagy and apoptosis was antagonized by co-treatment with chloroquine, an autophagy inhibitor. Our results indicate that MSKE can elicit an UPR that can eventually lead to apoptosis in prostate cancer cells.

  1. Muscadine Grape Skin Extract Induces an Unfolded Protein Response-Mediated Autophagy in Prostate Cancer Cells: A TMT-Based Quantitative Proteomic Analysis.

    Directory of Open Access Journals (Sweden)

    Liza J Burton

    Full Text Available Muscadine grape skin extract (MSKE is derived from muscadine grape (Vitis rotundifolia, a common red grape used to produce red wine. Endoplasmic reticulum (ER stress activates the unfolded protein response (UPR that serves as a survival mechanism to relieve ER stress and restore ER homeostasis. However, when persistent, ER stress can alter the cytoprotective functions of the UPR to promote autophagy and cell death. Although MSKE has been documented to induce apoptosis, it has not been linked to ER stress/UPR/autophagy. We hypothesized that MSKE may induce a severe ER stress response-mediated autophagy leading to apoptosis. As a model, we treated C4-2 prostate cancer cells with MSKE and performed a quantitative Tandem Mass Tag Isobaric Labeling proteomic analysis. ER stress response, autophagy and apoptosis were analyzed by western blot, acridine orange and TUNEL/Annexin V staining, respectively. Quantitative proteomics analysis indicated that ER stress response proteins, such as GRP78 were greatly elevated following treatment with MSKE. The up-regulation of pro-apoptotic markers PARP, caspase-12, cleaved caspase-3, -7, BAX and down-regulation of anti-apoptotic marker BCL2 was confirmed by Western blot analysis and apoptosis was visualized by increased TUNEL/Annexin V staining upon MSKE treatment. Moreover, increased acridine orange, and LC3B staining was detected in MSKE-treated cells, suggesting an ER stress/autophagy response. Finally, MSKE-mediated autophagy and apoptosis was antagonized by co-treatment with chloroquine, an autophagy inhibitor. Our results indicate that MSKE can elicit an UPR that can eventually lead to apoptosis in prostate cancer cells.

  2. Helveticoside is a biologically active component of the seed extract of Descurainia sophia and induces reciprocal gene regulation in A549 human lung cancer cells.

    Science.gov (United States)

    Kim, Bu-Yeo; Lee, Jun; Kim, No Soo

    2015-09-18

    Although the pharmacological activities of the seed extract of Descurainia sophia have been proven to be useful against cough, asthma, and edema, the biologically active components, particularly at the molecular level, remain elusive. Therefore, we aimed to identify the active component of an ethanol extract of D. sophia seeds (EEDS) by applying a systematic genomic approach. After treatment with EEDS, the dose-dependently expressed genes in A549 cells were used to query the Connectivity map to determine which small molecules could closely mimic EEDS in terms of whole gene expression. Gene ontology and pathway analyses were also performed to identify the functional involvement of the drug responsive genes. In addition, interaction network and enrichment map assays were implemented to measure the functional network structure of the drug-responsive genes. A Connectivity map analysis of differentially expressed genes resulted in the discovery of helveticoside as a candidate drug that induces a similar gene expression pattern to EEDS. We identified the presence of helveticoside in EEDS and determined that helveticoside was responsible for the dose-dependent gene expression induced by EEDS. Gene ontology and pathway analyses revealed that the metabolism and signaling processes in A549 cells were reciprocally regulated by helveticoside and inter-connected as functional modules. Additionally, in an ontological network analysis, diverse cancer type-related genes were found to be associated with the biological functions regulated by helveticoside. Using bioinformatic analyses, we confirmed that helveticoside is a biologically active component of EEDS that induces reciprocal regulation of metabolism and signaling processes. Our approach may provide novel insights to the herbal research field for identifying biologically active components from extracts.

  3. Effect of White Turmeric Extract (Curcuma zedoaria Using Zam-zam Solvent Compare with Ethanol Solvent Against Breast Cancer Cell T47D

    Directory of Open Access Journals (Sweden)

    Isna Hudaya

    2016-01-01

    Full Text Available Introduction: Curcuma zedoaria is one of the herbal plants potentially protects and cures many diseases, particularly as anti-cancer and anti-tumor. Anti-cancer active compounds of it are flavonoid, phenolic, and saponin. Objectives: This study aimed to explore the cytotoxicity of Curcuma zedoria extract (CZE. Methods: Experimental Quasi with post test non equivalent control group design on T47D cell line at Biology laboratory, Faculty of Medicine, Sultan Agung Islamic University, Semarang. The research was consisted of 2 groups, namely: intervention group with CZE zam-zam solvent and intervention group with CZE ethanol solvent given 10 different dosages each for 1.000 μg/mL; 500 μg/mL; 250 μg/mL; 125 μg/mL; 62.5 μg/mL; 31.25 μg/mL; 15.62 μg/mL; 7.81 μg/mL; 3.90 μg/mL; 1.95 μg/mL. Cytotoxicity test of IC50 using direct counting method and analyzed by probit analysis. Results: IC50 value of CZE in zam-zam and ethanol solvent were 28.24 μg/ml and 13.71 µg/ml respectively at the same 24 hours incubation period. Chi-square test revealed p value was 0.000 (α = 0.05, meaning that there was significant relationship. Conclusion: CZE activity using ethanol is highly active while CZE using zam-zam water is moderate and both of them have the toxicity on breast cancer cell. As the result, apoptosis process may occur.

  4. Effect of Neem Leaf Extract (Azadirachta indica) on c-Myc Oncogene Expression in 4T1 Breast Cancer Cells of BALB/c Mice.

    Science.gov (United States)

    Othman, Fauziah; Motalleb, Gholamreza; Lam Tsuey Peng, Sally; Rahmat, Asmah; Basri, Rusliza; Pei Pei, Chong

    2012-01-01

    Breast cancer is the most common cause of cancer-related deaths in women both worldwide and in Malaysia. Azadirachta indica (A. Juss), commonly known as neem, is one of the most versatile medicinal plants that has gained worldwide prominence due to its medicinal properties. However, the anticancer effect of ethanolic neem leaf extract against breast cancer has not been documented. The purpose of the present study is to investigate the effect of neem leaf extract on c-Myc oncogene expression in 4T1 breast cancer BALB/c mice. In this experimental study, A total of 48 female BALB/c mice were divided randomly into four groups of 12 mice per group: i.cancer control (CC) treated with 0.5% Tween 20 in PBS, ii. 0.5 µg/mL tamoxifen citrate (CT), iii. 250 mg/kg neem leaf extract (C250), and iv. 500 mg/kg neem leaf extract (C500). in situ reverse transcription polymerase chain reaction (in situ RT-PCR) was applied to evaluate suppression of c-Myc oncogene expression in breast cancer tissue. The C500 group showed significant (p<0.05) suppression of c-Myc oncogene expression compared to the CC group. c-Myc was found to be down regulated under the effect of 500 mg/kg ethanolic neem leaf extract.

  5. Liver Cancer Stem Cells

    OpenAIRE

    Sameh Mikhail; Aiwu Ruth He

    2011-01-01

    Hepatocellular carcinoma is the most common primary malignancy of the liver in adults. It is also the fifth most common solid cancer worldwide and the third leading cause of cancer-related death. Recent research supports that liver cancer is a disease of adult stem cells. From the models of experimental hepatocarcinogenesis, there may be at least three distinct cell lineages with progenitor properties susceptible to neoplastic transformation. Identification of specific cell surface markers fo...

  6. Cancer stem cell metabolism

    National Research Council Canada - National Science Library

    Peiris-Pagès, Maria; Martinez-Outschoorn, Ubaldo E; Pestell, Richard G; Sotgia, Federica; Lisanti, Michael P

    2016-01-01

    .... Cancer stem cells also seem to adapt their metabolism to microenvironmental changes by conveniently shifting energy production from one pathway to another, or by acquiring intermediate metabolic phenotypes...

  7. Phenolics extracted from tartary (Fagopyrum tartaricum L. Gaerth) buckwheat bran exhibit antioxidant activity, and an antiproliferative effect on human breast cancer MDA-MB-231 cells through the p38/MAP kinase pathway.

    Science.gov (United States)

    Li, Fuhua; Zhang, Xiaoli; Li, Yao; Lu, Keke; Yin, Ran; Ming, Jian

    2017-01-25

    Phenolics extracted from tartary buckwheat (Fagopyrum tartaricum L. Gaerth) bran were analyzed quantitatively and qualitatively. The bioactivity of the phenolic extracts was evaluated, such as the antioxidant activity, and the inhibition capacity on the growth of cancer cells. The molecular mechanism for the inhibitive effect on cancer cells was explored. Results indicated that tartary buckwheat bran phenolics mainly exist in a free form, and free phenolics were twice as abundant as bound phenolics. Free caffeic acid (119.75 μg per 100 mg DW) and bound rutin (51.66 μg per 100 mg DW) represented the main free and bound phenolic compounds, respectively. The free phenolic extract contributed to the major (>90%) antioxidant activities including the oxygen radical antioxidant capacity (ORAC) and cellular antioxidant activity (CAA). The free phenolic extract exhibited anticancer activity for human breast cancer MDA-MB-231 cells in a dose-dependent manner. This significant inhibition effect was achieved through the p38/MAP kinase pathway by inducing cell apoptosis (up-regulating p-p38 and p-ASK1 expressions and down-regulating TRAF2 and p-p53 expressions), and negatively regulating the progression of the cell cycle from the G1 to S phase (increased expression of p21 and suppressed expressions of PCNA, cyclin D1 and CDK4). All these results indicated that tartary buckwheat bran could be a rich resource of natural antioxidants and inhibitors for the growth of MDA-MB-231 cells.

  8. Biofabrication of Ag nanoparticles using Sterculia foetida L. seed extract and their toxic potential against mosquito vectors and HeLa cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Rajasekharreddy, Pala; Rani, Pathipati Usha, E-mail: usharani65@yahoo.com

    2014-06-01

    A one-step and eco-friendly process for the synthesis of silver-(protein-lipid) nanoparticles (Ag-PL NPs) (core–shell) has been developed using the seed extract from wild Indian Almond tree, Sterculia foetida (L.) (Sterculiaceae). The reaction temperature played a major role in controlling the size and shell formation of NPs. The amount of NPs synthesized and qualitative characterization was done by UV–vis spectroscopy and transmission electron microscopy (TEM), respectively. TEM studies exhibited controlled dispersity of spherical shaped NPs with an average size of 6.9 ± 0.2 nm. Selected area electron diffraction (SAED) and X-ray diffraction (XRD) revealed ‘fcc’ phase and crystallinity of the particles. X-ray photoelectron spectroscopy (XPS) was used to identify the protein–lipid (PL) bilayer that appears as a shell around the Ag core particles. The thermal stability of the Ag-PL NPs was examined using thermogravimetric analysis (TGA). Further analysis was carried out by using Fourier transform infrared spectroscopy (FTIR), where the spectra provided evidence for the presence of proteins and lipid moieties ((2n-octylcycloprop-1-enyl)-octanoic acid (I)), and their role in synthesis and stabilization of Ag NPs. This is the first report of plant seed assisted synthesis of PL conjugated Ag NPs. These formed Ag-PL NPs showed potential mosquito larvicidal activity against Aedes aegypti (L.), Anopheles stephensi Liston and Culex quinquefasciatus Say. These Ag-PL NPs can also act as promising agents in cancer therapy. They exhibited anti-proliferative activity against HeLa cancer cell lines and a promising toxicity was observed in a dose dependent manner. Toxicity studies were further supported by the cellular DNA fragmentation in the Ag-PL NPs treated HeLa cells. - Highlights: • Green synthesis of protein-lipid conjugated Ag NPs using S. foetida L. seed extract. • S. foetida seed extract acted as good reducing and stabilizing agent for Ag NPs. • XPS and

  9. Apoptotic effects of extract from Cnidium monnieri (L.) Cusson by adenosine monosphosphate-activated protein kinase-independent pathway in HCT116 colon cancer cells.

    Science.gov (United States)

    Lim, Eun Gyeong; Kim, Guen Tae; Lee, Se Hee; Kim, Sang-Yong; Kim, Young Min

    2016-06-01

    Colon cancer, a common malignancy, can occur due to poor eating habits and increasing age. Consequently, careful regulation of eating habits may serve as a possible method for preventing the occurrence or progression of colon cancer. Extracts of the fruit of Cnidium monnieri (L.) Cusson are well‑known as an effective herbal medicine for the treatment of pain in female genitalia and carbuncle. However, there have been no studies on the apoptotic effects of Cnidium monnieri (L.) Cusson (CME). Adenosine monophosphate‑activated protein kinase (AMPK), the major regulator of energy metabolism, is activated by metabolic stress, including hypoxia and glucose deprivation. Activation of AMPK inhibits cell proliferation and induces apoptosis through the inhibition of phosphorylated (p)‑Akt and control of B‑cell lymphoma 2 (Bcl‑2) family members. The pro‑apoptotic proteins Bcl‑2‑associated X protein (Bax) and Bcl‑2‑homologous antagonist killer (Bak), are activated by their translocation to mitochondria from the cytosol. Translocation of Bax/Bak induces outer membrane permeabilization and is likely to lead to apoptosis through cytochrome C release and caspase activity. In the present study, the apoptotic effects and influence on mitochondria‑mediated apoptotic proteins of CME in HCT116 cells were assessed. We hypothesized that CME may have an effect on the inhibition of p‑Akt in an AMPK‑independent pathway. The present study demonstrated that CME induced the release of LDH and apoptosis through its inhibition of p‑Akt to control Bcl‑2 and activate Bax and Bak. Co‑treatment with CME and AMPK inhibitors showed that CME‑induced apoptosis does not occurr through a AMPK‑dependent pathway. Therefore, the present study determined, for the first time, that CME induced apoptosis as a result of causing metabolic stresses due to directly regulation of the de‑phosphorylation of Akt, whereas it did not control the AMPK-dependent pathway in HCT116

  10. Basal cell cancer (image)

    Science.gov (United States)

    ... biopsy is needed to prove the diagnosis of basal cell carcinoma. Treatment varies depending on the size, depth, and location of the cancer. Early treatment by a dermatologist may result in a cure ... is required to watch for new sites of basal cell cancer.

  11. Validation of the Antiproliferative Effects of Organic Extracts from the Green Husk of Juglans regia L. on PC-3 Human Prostate Cancer Cells by Assessment of Apoptosis-Related Genes

    Directory of Open Access Journals (Sweden)

    Ali A. Alshatwi

    2012-01-01

    Full Text Available With the increased use of plant-based cancer chemotherapy, exploring the antiproliferative effects of phytochemicals for anticancer drug design has gained considerable attention worldwide. This study was undertaken to investigate the effect of walnut green husk extracts on cell proliferation and to determine the possible molecular mechanism of extract-induced cell death by quantifying the expression of Bcl-2, Bax, caspases-3, and Tp53. PC-3 human prostate cancer cells. In this study, we found that green husk extracts suppressed proliferation and induced apoptosis in a dose- and time-dependent manner by modulating expression of apoptosis-related genes. This involved DNA fragmentation (determined by TUNEL assay and significant changes in levels of mRNA and the expression of corresponding proteins. An increase in expressions of Bax, caspase-3, and tp53 genes and their corresponding proteins was detected using real-time PCR and western blot analysis in PC-3 cells treated with the green husk organic extracts. In contrast, Bcl2 expression was downregulated after exposure to the extracts. Our data suggest the presence of bioactive compound(s in walnut green husks that are capable of killing prostate carcinoma cells by inducing apoptosis and that the husks are a candidate source of anticancer drugs.

  12. Targeting beta-catenin signaling to induce apoptosis in human breast cancer cells by z-guggulsterone and Gugulipid extract of Ayurvedic medicine plant Commiphora mukul.

    Science.gov (United States)

    Jiang, Guoqin; Xiao, Xiao; Zeng, Yan; Nagabhushanam, Kalyanam; Majeed, Muhammed; Xiao, Dong

    2013-08-03

    z-Guggulsterone (z-Gug) and Gugulipid (GL) have been used to treat a variety of ailments. We now report their anti-cancer effect and mechanism against human breast cancer. Using the human estrogen receptor-positive (MCF-7) and triple-negative (MDA-MB-231) breast cancer cells as well as the normal human mammary epithelial cell line (HMEC), we evaluated the anti-breast-cancer efficacy and apoptosis inducing activity of GL. We determined the cellular and molecular mechanism of GL-inhibited breast cancer cell growth. GL significantly inhibited growth of MCF-7 and MDA-MB-231 cells with an IC50~2 μM at pharmacologically relevant concentrations standardized to its major active constituent z-Gug. The GL-induced growth inhibition correlated with apoptosis induction as evidenced by an increase in cytoplasmic histone-associated DNA fragmentation and caspase 3 activity. The GL-induced apoptosis was associated with down-regulation of the β-Catenin signaling pathway. The decreased expression of Wnt/β-Catenin targeting genes, such as cyclin D1, C-myc and survivin, and the inhibition of the activity of the transcription factor (T-cell factor 4, TCF-4) were observed in GL-treated breast cancer cells. The GL treatment resulted in a significant reduction of β-Catenin /TCF-4 complex in both of the cancer cells. The GL-induced apoptotic cell death was significantly enhanced by RNA Interference of β-Catenin and TCF-4. On the other hand, the normal human mammary epithelial cell HMEC, compared with the human breast cancer cells, is significantly more resistant to growth inhibition and apoptosis induction by GL. The present study indicates that the β-Catenin signaling pathway is the target for GL-induced growth inhibition and apoptosis in human breast cancer.

  13. Therapeutic effects of gold nanoparticles synthesized using Musa paradisiaca peel extract against multiple antibiotic resistant Enterococcus faecalis biofilms and human lung cancer cells (A549).

    Science.gov (United States)

    Vijayakumar, S; Vaseeharan, B; Malaikozhundan, B; Gopi, N; Ekambaram, P; Pachaiappan, R; Velusamy, P; Murugan, K; Benelli, G; Suresh Kumar, R; Suriyanarayanamoorthy, M

    2017-01-01

    Botanical-mediated synthesis of nanomaterials is currently emerging as a cheap and eco-friendly nanotechnology, since it does not involve the use of toxic chemicals. In the present study, we focused on the synthesis of gold nanoparticles using the aqueous peel extract of Musa paradisiaca (MPPE-AuNPs) following a facile and cheap fabrication process. The green synthesized MPPE-AuNPs were bio-physically characterized by UV-Vis spectroscopy, FTIR, XRD, TEM, Zeta potential analysis and EDX. MPPE-AuNPs were crystalline in nature, spherical to triangular in shape, with particle size ranging within 50 nm. The biofilm inhibition activity of MPPE-AuNPs was higher against multiple antibiotic resistant (MARS) Gram-positive Enterococcus faecalis. Light and confocal laser scanning microscopic observations evidenced that the MPPE-AuNPs effectively inhibited the biofilm of E. faecalis when tested at 100 μg mL-1. Cytotoxicity studies demonstrated that MPPE-AuNPs were effective in inhibiting the viability of human A549 lung cancer cells at higher concentrations of 100 μg mL-1. The morphological changes in the MPPE-AuNPs treated A549 lung cancer cells were visualized under phase-contrast microscopy. Furthermore, the ecotoxicity of MPPE-AuNPs on the freshwater micro crustacean Ceriodaphnia cornuta were evaluated. Notably, no mortality was recorded in MPPE-AuNPs treated C. cornuta at 250 μg mL-1. This study concludes that MPPE-AuNPs are non-toxic, eco-friendly and act as a multipurpose potential biomaterial for biomedical applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Prostate cancer stem cells.

    Science.gov (United States)

    Tu, Shi-Ming; Lin, Sue-Hwa

    2012-06-01

    Stem cells have long been implicated in prostate gland formation. The prostate undergoes regression after androgen deprivation and regeneration after testosterone replacement. Regenerative studies suggest that these cells are found in the proximal ducts and basal layer of the prostate. Many characteristics of prostate cancer indicate that it originates from stem cells. For example, the putative androgen receptor-negative (AR(-)) status of prostate stem cells renders them inherently insensitive to androgen blockade therapy. The androgen-regulated gene fusion TMPRSS2-ERG could be used to clarify both the cells of origin and the evolution of prostate cancer cells. In this review, we show that the hypothesis that distinct subtypes of cancer result from abnormalities within specific cell types-the stem cell theory of cancer-may instigate a major paradigm shift in cancer research and therapy. Ultimately, the stem cell theory of cancers will affect how we practice clinical oncology: our diagnosis, monitoring, and therapy of prostate and other cancers. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Investigation of Astragalus honey and propolis extract's cytotoxic effect on two human cancer cell lines and their oncogen and proapoptotic gene expression profiles

    OpenAIRE

    Hojjat Sadeghi-Aliabadi; Jamal Hamzeh; Mina Mirian

    2015-01-01

    Background: Cancer is one of the major fatal human diseases. Natural products have been used in the treatment of cancer for long time. Bee products including honey and propolis have been introduced for malignancy treatment in recent decades. In this study cytotoxicity of bee products and their effects on the expression of proapoptotic genes have been investigated. Materials and Methods: Cytotoxic effects of Astragalus honey, ethanol extract of propolis and a sugar solution (as control) ag...

  16. Cytotoxic Effect and Constituent Profile of Alkaloid Fractions from Ethanolic Extract of Ficus septica Burm. f. Leaves on T47D Breast Cancer Cells.

    Science.gov (United States)

    Nugroho, Agung Endro; Akbar, Fiki Fatihah; Wiyani, Anggie; Sudarsono

    2015-01-01

    The study aimed to investigate the profile of alkaloids in two ethyl acetate soluble fractions, namely fractions A and B from an ethanolic extract of Ficus septica leaves and cytotoxic effect on T47D breast cancer cells. Preparation of both fractions involved maceration of leaves with 70% (v/v) ethanol, filtration with Al2O3, precipitation with 0.1 N HCl, Mayer reagent, and 0.1 N NaOH, and also partition with ethyl acetate. Qualitative thin layer chromatography (TLC) was conducted to determine the profile of alkaloids in the two fractions, using alkaloid specific reagents such as Dragendorff, sodium nitrite, and Van Urk-Salkowski. Cytotoxic effects of both fractions on T47D cells were evaluated using MTT assay with a concentration series of 1.56; 3.12; 6.25; 12.5; 25 and 50 μg/mL. The TLC test showed that fractions A and B contained alkaloids with Rx values of 0.74 and 0.80 for fraction A and 0.74, 0.84, 0.92 for fraction B with regard to yohimbine using the mobile phase of n-buthanol:glacial acetic acid:distilled water (3:1:1 v/v/v). Moreover, an indole alkaloid was detected with Rx values of 0.80 and 0.84, respectively. Fractions A and B exhibited high cytotoxic effects on T47D cells with IC50 values of 2.57 and 2.73 μg/mL, respectively. In conclusion, overall the results of this study showed that fractions of Ficus septica contain alkaloids including indole alkaloid or its derivatives and possess a cytotoxic effect on T47D cells. This research supports the idea that alkaloids in F. septica have anticancer activity.

  17. Breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    Thomas W Owens

    2013-08-01

    Full Text Available Cancer metastasis, resistance to therapies and disease recurrence are significant hurdles to successful treatment of breast cancer. Identifying mechanisms by which cancer spreads, survives treatment regimes and regenerates more aggressive tumours are critical to improving patient survival. Substantial evidence gathered over the last 10 years suggests that breast cancer progression and recurrence is supported by cancer stem cells (CSCs. Understanding how CSCs form and how they contribute to the pathology of breast cancer will greatly aid the pursuit of novel therapies targeted at eliminating these cells. This review will summarise what is currently known about the origins of breast CSCs, their role in disease progression and ways in which they may be targeted therapeutically.

  18. Extracts from Vatica diospyroides Type SS Fruit Show Low Dose Activity against MDA-MB-468 Breast Cancer Cell-Line via Apoptotic Action

    Directory of Open Access Journals (Sweden)

    Theera Srisawat

    2014-01-01

    Full Text Available Very strong antiproliferative action of V. diospyroides type SS fruit extracts (IC50 range of 1.60-17.45 µg/mL in MDA-MB-468 cell-line was observed in an MTT assay. After dosing of an extract concentration at half IC50 to cell line for 24 to 72 hours, treated cells were subjected to Annexin V-FITC/PI binding assay, followed by FACS and western blot analyses. Significant apoptotic death was observed with all extract treatments and both exposure times. Dosing with acetone extract of pericarp and cotyledon induced the highest apoptotic populations (33 and 32%, resp., with the lowest populations of viable cells (65 and 67%, resp.. During 24 to 72 hours of dosing with methanolic extract of pericarp, the populations of viable and early apoptotic cells decreased significantly from 72.40 to 71.32% and from 12.00 to 6.36%, respectively, while the late apoptotic and nonviable cell populations continuously increased from 15.30 to 19.18% and from 0.30 to 3.14%, respectively. The expression of Bax increased within 12–48 hours of dosing, confirming apoptosis induced by time-dependent responses. The mutant p53 of MDA-MB-468 cells was expressed. Our results indicate that apoptosis and time-dependent therapeutic actions contribute to the cytotoxic effects of V. diospyroides type SS fruit on MDA-MB-468 cell.

  19. Synthesis of silver nanoparticles using Solanum trilobatum fruits extract and its antibacterial, cytotoxic activity against human breast cancer cell line MCF 7

    Science.gov (United States)

    Ramar, Manikandan; Manikandan, Beulaja; Marimuthu, Prabhu Narayanan; Raman, Thiagarajan; Mahalingam, Anjugam; Subramanian, Palanisamy; Karthick, Saravanan; Munusamy, Arumugam

    2015-04-01

    In the present study, we have synthesized silver nanoparticles by a simple and eco-friendly method using unripe fruits of Solanum trilobatum. The aqueous silver ions when exposed to unripe fruits extract were reduced and stabilized over long time resulting in biosynthesis of surface functionalized silver nanoparticles. The bio-reduced silver nanoparticles were characterized by UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDX) and X-ray diffraction (XRD). These biologically synthesized silver nanoparticles were tested for its antibacterial activity against few human pathogenic bacteria including Gram-positive (Streptococcus mutans, Enterococcus faecalis) and Gram-negative (Escherichia coli, Klebsiella pneumoniae) bacteria. In addition, we also demonstrated anticancer activity of these nanoparticles in vitro against human breast cancer cell line (MCF 7) using MTT, nuclear morphology assay, Western blot and RT-PCR expression. These results taken together show the potential applications of biosynthesized silver nanoparticles using S. trilobatum fruits.

  20. Resolution and identification of scalemic caged xanthones from the leaf extract of Garcinia propinqua having potent cytotoxicities against colon cancer cells.

    Science.gov (United States)

    Sriyatep, Teerayut; Tantapakul, Cholpisut; Andersen, Raymond J; Patrick, Brian O; Pyne, Stephen G; Muanprasat, Chatchai; Seemakhan, Sawinee; Borwornpinyo, Suparerk; Laphookhieo, Surat

    2018-01-01

    A new scalemic 8,8a-dihydro caged xanthone (1) was isolated from the leaf extract of Garcinia propinqua. Five other known natural products, the three caged xanthones (2, 5 and 6) and the two neocaged xanthones, (3 and 4) were also isolated as scalemic mixtures. Their structures were characterized by spectroscopic methods. The enantiomeric ratios (er) of compounds 1-6 ranged from 1:0.7 to 1:0.9. These compounds were also resolved by semipreparative chiral HPLC. The absolute configurations of (+)-2 and (+)-3 were determined by single-crystal X-ray diffraction analysis using Cu Kα radiation while the absolute configurations of the other compounds were determined by comparisons of their ECD spectra. Compounds (-)-4, (+)-4, (-)-5, (+)-5, and (-)-6 showed potent cytotoxicities against a colon cancer cell line HCT116 with IC 50 values of 2.60, 7.02, 1.47, 3.37, and 4.14μM, respectively, which were better than the standard control doxorubicin (IC 50 9.74μM). Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  1. Growth Inhibition and Apoptosis Induction of Essential Oils and Extracts of Nepeta cataria L. on Human Prostatic and Breast Cancer Cell Lines.

    Science.gov (United States)

    Emami, Seyed Ahmad; Asili, Javad; Hossein Nia, Shima; Yazdian-Robati, Rezvan; Sahranavard, Mehrdad; Tayarani-Najaran, Zahra

    2016-01-01

    Nepeta cataria L. has been used in traditional medicine of some countries. Here the cytotoxic and apoptogenic activity of methanol extracts, n-hexane, dichloromethane, ethyl acetate, n-butanol, and acqueous extracts and the essential oil obtained from the aerial parts of the plant were evaluated with PC3, DU-145 and MCF-7 cell lines. Cell viability, histograms of PI stained fragmented DNA in apoptotic cells and Western blot analysis of proteins involved in the cascade of apoptosis were compared in all samples. Thirty components were identified as volatile, representing 99.7% of essential oil composition after GC-MS analysis of the oil obtained from aerial parts of the N. cataria by hydro-distillation. The major oil components of the essential oil were nepetalactone stereoisomers. Comparing IC50 values showed estrogen receptor positive PC3 cells were more sensitive to the cytotoxic effects of N. cataria in comparison with low hormone-receptor presenting DU-145 cells. Among multiple extracts and essential oils of the plant, only the ethyl acetate extract could significantly decrease cell viability in PC3 cells, in a concentration dependent manner. Ethyl acetate extract of N. cataria treated cells showed a sub-G1 peak in PC3 cells in a concentration dependent manner that indicates the involvement of an apoptotic process in ethyl acetate extract-induced cell death. Western blotting analysis showed that in PC3 cells treated with ethyl acetate (48 h) caspase 3 and PARP were cleaved to active forms. Overall, the results suggest that further analytical elucidation of N. cataria in respect to finding new cytotoxic chemicals with anti-tumor activity is warranted.

  2. The effect of hydroalcoholic Ziziphus spina-christi leaf extract on viability of breast cancer cell line (MCF7 and evaluation of Bax and Bcl2 genes expression level

    Directory of Open Access Journals (Sweden)

    Rahim Ahmadi

    2017-11-01

    Full Text Available Background: Studies have revealed that the Sidr (Ziziphus spina-christi leaf has anticancer effects. The aim of this study was to investigate the effects of hydroalcoholic Sidr leaf extract on MCF7 cell line viability and evaluation of Bax and Bcl2 genes expression level. Materials and Methods: In this laboratory-experimental study, MCF cells were randomly divided into control group and groups exposed to 0.001, 0.01, 0.1, 1 and 10 mg/mL of the Sidr leaf hydroalcoholic extract. The cytotoxic effect of the extract was measured using the MTT assay method. Also, the real-time polymerase chain reaction method was used to evaluate Bax and Bcl2 genes expression levels. Results: Viability of the MCF7 cells did not significantly change in group exposed to 0.001 mg/mL of the extract; however, it was significantly decreased in groups exposed to 0.01, 0.1, 1 and 10 mg/mL of the extract (P<0.01, P<0.05, P<0.001 and P<0.001, respectively. The expression levels of Bcl2 and Bax genes were significantly decreased and increased respectively in MCF7 cells exposed to 1mg/mL of the extract (P<0.01 and P<0.001, respectively. Conclusion: The appropriate doses of the hydroalcoholic Sidr leaf extract have cytotoxic effects on MCF7 cells by inducing apoptosis. So, further research on the anticancer effects of Sidr on breast cancer has a significant place in breast cancer treatment.

  3. Food extracts consumed in Mediterranean countries and East Asia reduce protein concentrations of androgen receptor, phospho-protein kinase B, and phospho-cytosolic phospholipase A(2)alpha in human prostate cancer cells.

    Science.gov (United States)

    Singh, Jaskirat; Xie, Chanlu; Yao, Mu; Hua, Sheng; Vignarajan, Soma; Jardine, Greg; Hambly, Brett D; Sved, Paul; Dong, Qihan

    2010-04-01

    Active surveillance is an emerging management option for the rising number of men with low-grade, clinically localized prostate cancer. However, 30-40% of men on active surveillance will progress to high-grade disease over 5 y. With the ultimate aim of developing a food-based chemoprevention strategy to retard cancer progression in these otherwise healthy men, we have developed a blend of food extracts commonly consumed in Mediterranean countries and East Asia. The effect of the food extracts known as Blueberry Punch (BBP) on prostate cancer cell growth and key signaling pathways were examined in vitro and in vivo. BBP reduced prostate cancer cell growth in a dose-dependent manner (0.08-2.5%) at 72 h in vitro due to the reduction in cell proliferation and viability. Prostate cancer cell xenograft-bearing mice, administered 10% BBP in drinking water for 2 wk, had a 25% reduction in tumor volume compared with the control (water only). In vitro, BBP reduced protein concentrations in 3 signaling pathways necessary for the proliferation and survival of prostate cancer cells, namely androgen receptor, phospho-protein kinase B/protein kinase B, and phospho-cytosolic phospholipase A(2)alpha. The downstream effectors of these pathways, including prostate-specific antigen and glycogen synthase kinase 3beta, were also reduced. Thus, this palatable food supplement is a potential candidate for testing in clinical trials and may ultimately prove effective in retarding the progression of low-grade, early-stage prostate cancer in men managed by active surveillance.

  4. Flavonoid C-glucosides Derived from Flax Straw Extracts Reduce Human Breast Cancer Cell Growth In vitro and Induce Apoptosis.

    Science.gov (United States)

    Czemplik, Magdalena; Mierziak, Justyna; Szopa, Jan; Kulma, Anna

    2016-01-01

    Flax straw of flax varieties that are grown for oil production is a by product which represents a considerable biomass source. Therefore, its potential application for human use is of high interest. Our research has revealed that flax straw is rich in flavonoid C-glucosides, including vitexin, orientin, and isoorientin. The objective of this study was to evaluate the cytotoxicity and possible proapoptotic effect of flax straw derived C-glucosides of flavonoids in the human breast adenocarcinoma cell line (MCF-7). The effects of flax straw derived flavonoid C-glucosides on cell proliferation of MCF-7 cells were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) and sulforhodamine B assays. The expression of apoptosis-related genes was assessed by real-time PCR. Our data revealed that flax C-glucosides as well as pure compounds are cytotoxic toward MCF-7 cells and inhibit their proliferation. Moreover, the induction of apoptosis was correlated with the changes in the mRNA level of pro-apoptotic genes. Increased expression of bax and caspase-7, -8, and -9 and decreased mRNA expression of bcl-2 was observed, whereas the mRNA levels of p53 and mdm2 were not altered. These results clearly demonstrated that flax straw metabolites effectively induced growth inhibition and apoptosis in human breast adenocarcinoma cells.

  5. Flavonoid C-glucosides derived from flax straw extracts reduce human breast cancer cell growth in vitro and induce apoptosis.

    Directory of Open Access Journals (Sweden)

    Magdalena Czemplik

    2016-08-01

    Full Text Available Flax straw of flax varieties that are grown for oil production is a byproduct which represents a considerable biomass source. Therefore its potential application for human use is of high interest. Our research has revealed that flax straw is rich in flavonoid C-glucosides, including vitexin, orientin and isoorientin. The objective of this study was to evaluate the cytotoxicity and possible proapoptotic effect of flax straw derived C-glucosides of flavonoids in the human breast adenocarcinoma cell line (MCF-7. The effects of flax straw derived flavonoid C-glucosides on cell proliferation of MCF-7 cells were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT and sulforhodamine B (SRB assays. The expression of apoptosis-related genes was assessed by real-time PCR. Our data revealed that flax C-glucosides as well as pure compounds are cytotoxic towards MCF-7 cells and inhibit their proliferation. Moreover, the induction of apoptosis was correlated with the changes in the mRNA level of pro-apoptotic genes. Increased expression of bax and caspase-7, -8, and -9 and decreased mRNA expression of bcl-2 was observed, whereas the mRNA levels of p53 and mdm2 were not altered. These results clearly demonstrated that flax straw metabolites effectively induced growth inhibition and apoptosis in human breast adenocarcinoma cells.

  6. Potent in vitro anti-proliferative, apoptotic and anti-oxidative activities of semi-purified Job's tears (Coix lachryma-jobi Linn.) extracts from different preparation methods on 5 human cancer cell lines.

    Science.gov (United States)

    Manosroi, Aranya; Sainakham, Mathukorn; Chankhampan, Charinya; Abe, Masahiko; Manosroi, Worapaka; Manosroi, Jiradej

    2016-07-01

    Job's tears (Coix lacryma-jobi Linn.) is commonly used as an herbal medicine. The low incidence of cancer has been observed in the area of China where regularly consume Job's tears. The effects of preparation methods of Job's tears on anti-cancer activities were investigated. Potent in vitro anti-proliferative, apoptotic and anti-oxidative activities of semi-purified Job's tears extracts from different preparation methods on 5 human cancer cell lines comparing with standards and commercial product were observed. To study the anti-proliferative, apoptotic and anti-oxidative activities of semi-purified Job's tear extracts from different preparation methods on 5 human cancer cell lines. The crude methanolic extracts of non-cooked, steamed and roasted Job's tears cultivars were prepared and further semi-purified by liquid-liquid extraction techniques. Both of crude and semi-purified extracts were tested for anti-proliferative, apoptotic induction, anti-oxidative activities and phytochemicals content. The highest yields of crude and-purified extracts were 4.60% and 1.46%, respectively. In crude extracts, the steamed whole Thai Black Loei Job's tears (W-TBL-S1) extract showed the highest anti-proliferative activity in mouth epidermal carcinoma cell (KB) at the IC50 of 43.61±0.76μg/ml (0.005 folds of doxorubicin), whereas the roasted whole Laos White Loei Job's tears (W-LWL-R2) extract showed the highest apoptotic activity in cervical adenocarcinoma (HeLa) at 21.52±1.50% (0.22 and 15.05 folds of doxorubicin and commercial product, respectively). After liquid-liquid extraction, almost all of the semi-purified extracts showed increases in anti-proliferative activity. Ethyl acetate fraction of the roasted whole Laos White Loei Job's tears (W-LWL-R2) showed the highest anti-proliferative activity in HeLa cell at the IC50 of 0.97±0.82μg/ml (7.82 and 45.39 folds of doxorubicin and crude extract, respectively) and apoptotic activity of 18.77±6.31% (0.19 folds of

  7. Selective killing of cancer cells by leaf extract of Ashwagandha: identification of a tumor-inhibitory factor and the first molecular insights to its effect.

    Science.gov (United States)

    Widodo, Nashi; Kaur, Kamaljit; Shrestha, Bhupal G; Takagi, Yasuomi; Ishii, Tetsuro; Wadhwa, Renu; Kaul, Sunil C

    2007-04-01

    Ashwagandha is regarded as a wonder shrub of India and is commonly used in Ayurvedic medicine and health tonics that claim its variety of health-promoting effects. Surprisingly, these claims are not well supported by adequate studies, and the molecular mechanisms of its action remain largely unexplored to date. We undertook a study to identify and characterize the antitumor activity of the leaf extract of ashwagandha. Selective tumor-inhibitory activity of the leaf extract (i-Extract) was identified by in vivo tumor formation assays in nude mice and by in vitro growth assays of normal and human transformed cells. To investigate the cellular targets of i-Extract, we adopted a gene silencing approach using a selected small hairpin RNA library and found that p53 is required for the killing activity of i-Extract. By molecular analysis of p53 function in normal and a variety of tumor cells, we found that it is selectively activated in tumor cells, causing either their growth arrest or apoptosis. By fractionation, purification, and structural analysis of the i-Extract constituents, we have identified its p53-activating tumor-inhibiting factor as with a none. We provide the first molecular evidence that the leaf extract of ashwagandha selectively kills tumor cells and, thus, is a natural source for safe anticancer medicine.

  8. Condurango (Gonolobus condurango Extract Activates Fas Receptor and Depolarizes Mitochondrial Membrane Potential to Induce ROS-dependent Apoptosis in Cancer Cells in vitro CE-treatment on HeLa: a ROS-dependent mechanism

    Directory of Open Access Journals (Sweden)

    Kausik Bishayee

    2015-09-01

    Full Text Available Objectives: Condurango (Gonolobus condurango extract is used by complementary and alternative medicine (CAM practitioners as a traditional medicine, including homeopathy, mainly for the treatment of syphilis. Condurango bark extract is also known to reduce tumor volume, but the underlying molecular mechanisms still remain unclear. Methods: Using a cervical cancer cell line (HeLa as our model, the molecular events behind condurango extract’s (CE’s anticancer effect were investigated by using flow cytometry, immunoblotting and reverse transcriptase-polymerase chain reaction (RT-PCR. Other included cell types were prostate cancer cells (PC3, transformed liver cells (WRL-68, and peripheral blood mononuclear cells (PBMCs. Results: Condurango extract (CE was found to be cytotoxic against target cells, and this was significantly deactivated in the presence of N-acetyl cysteine (NAC, a scavenger of reactive oxygen species (ROS, suggesting that its action could be mediated through ROS generation. CE caused an increase in the HeLa cell population containing deoxyribonucleic acid (DNA damage at the G zero/Growth 1 (G0/G1 stage. Further, CE increased the tumor necrosis factor alpha (TNF-α and the fas receptor (FasR levels both at the ribonucleic acid (RNA and the protein levels, indicating that CE might have a cytotoxic mechanism of action. CE also triggered a sharp decrease in the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB both at the RNA and the protein levels, a possible route to attenuation of B-cell lymphoma 2 (Bcl-2, and caused an opening of the mitochondrial membrane’s permeability transition (MPT pores, thus enhancing caspase activities. Conclusion: Overall, our results suggest possible pathways for CE mediated cytotoxicity in model cancer cells.

  9. Hurthle Cell Cancer

    Science.gov (United States)

    ... breath Hurthle cell cancer Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  10. Basal cell skin cancer

    Science.gov (United States)

    Basal cell skin cancer almost never spreads. If it is left untreated, it may spread into surrounding areas and nearby tissues and bone. In these cases, treatment can injure the appearance of the skin.

  11. Aqueous cinnamon extract (ACE-c) from the bark of Cinnamomum cassia causes apoptosis in human cervical cancer cell line (SiHa) through loss of mitochondrial membrane potential.

    Science.gov (United States)

    Koppikar, Soumya J; Choudhari, Amit S; Suryavanshi, Snehal A; Kumari, Shweta; Chattopadhyay, Samit; Kaul-Ghanekar, Ruchika

    2010-05-18

    Chemoprevention, which includes the use of synthetic or natural agents (alone or in combination) to block the development of cancer in human beings, is an extremely promising strategy for cancer prevention. Cinnamon is one of the most widely used herbal medicines with diverse biological activities including anti-tumor activity. In the present study, we have reported the anti-neoplastic activity of cinnamon in cervical cancer cell line, SiHa. The aqueous cinnamon extract (ACE-c) was analyzed for its cinnamaldehyde content by HPTLC analysis. The polyphenol content of ACE-c was measured by Folin-Ciocalteau method. Cytotoxicity analysis was performed by MTT assay. We studied the effect of cinnamon on growth kinetics by performing growth curve, colony formation and soft agar assays. The cells treated with ACE-c were analyzed for wound healing assay as well as for matrix metalloproteinase-2 (MMP-2) expression at mRNA and protein level by RT-PCR and zymography, respectively. Her-2 protein expression was analyzed in the control and ACE-c treated samples by immunoblotting as well as confocal microscopy. Apoptosis studies and calcium signaling assays were analyzed by FACS. Loss of mitochondrial membrane potential (Deltapsim) in cinnamon treated cells was studied by JC-1 staining and analyzed by confocal microscopy as well as FACS. Cinnamon alters the growth kinetics of SiHa cells in a dose-dependent manner. Cells treated with ACE-c exhibited reduced number of colonies compared to the control cells. The treated cells exhibited reduced migration potential that could be explained due to downregulation of MMP-2 expression. Interestingly, the expression of Her-2 oncoprotein was significantly reduced in the presence of ACE-c. Cinnamon extract induced apoptosis in the cervical cancer cells through increase in intracellular calcium signaling as well as loss of mitochondrial membrane potential. Cinnamon could be used as a potent chemopreventive drug in cervical cancer.

  12. Evaluation of p53 and Bcl-2 genes and proteins expression in human breast cancer T47D cells treated with extracts of Astrodaucus persicus (Boiss. Drude in comparison to Tamoxifen

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    E Azizi

    2009-10-01

    Full Text Available "n "nBackground and purpose of the study:Screening of different plant components for new anticancer drugs is one of the main research activities throughout the world. In this study, the anticancer effects of Astrodaucus persicus, an Iranian species of family of Umbelliferae, in human breast cancer T47D cells was investigated. Also since tumorigenesis is thought to result from a series of progressive gene alterations, including activa tion of oncogenes and inactivation of tumor suppres sor genes, expression of two such genes, p53 and Bcl-2 that are believed to play a crucial role in tumorigenesis and cell death were determined. "nMaterials and Methods: The p53 and Bcl-2 genes and proteins expression alterations in T47D cells at RNA synthesis level was studied by using RT-PCR analysis and protein synthesis using immunocytochemistry technique. "nResults: p53 gene expression increased significantly in the presence of both plant extracts but Bcl-2 expression increased significantly in the presence of aerial and decreased significantly in the presence of root extract. In addition, treatment of T47D cells with plant extracts decreased the nuclear staining of p53 and cytoplasmic staining of Bcl-2 proteins. "nConclusion: These results suggest that the methanolic extracts of Astrodaucus persicus especially its root extract may contains bioactive compounds, probably coumarins that prevents proliferation of T47D breast carcinoma cells by mechanisms such as apoptosis. These data are the first report on the possible molecular mechanisms of action of Astrodaucus persicus extracts in breast cancer cell proliferation.

  13. Lipid extraction from isolated single nerve cells

    Science.gov (United States)

    Krasnov, I. V.

    1977-01-01

    A method of extracting lipids from single neurons isolated from lyophilized tissue is described. The method permits the simultaneous extraction of lipids from 30-40 nerve cells and for each cell provides equal conditions of solvent removal at the conclusion of extraction.

  14. A hepatoprotective Lindera obtusiloba extract suppresses growth and attenuates insulin like growth factor-1 receptor signaling and NF-kappaB activity in human liver cancer cell lines

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    Stroh Thorsten

    2011-05-01

    Full Text Available Abstract Background In traditional Chinese and Korean medicine, an aqueous extract derived from wood and bark of the Japanese spice bush Lindera obtusiloba (L.obtusiloba is applied to treat inflammations and chronic liver diseases including hepatocellular carcinoma. We previously demonstrated anti-fibrotic effects of L.obtusiloba extract in hepatic stellate cells. Thus, we here consequently examine anti-neoplastic effects of L.obtusiloba extract on human hepatocellular carcinoma (HCC cell lines and the signaling pathways involved. Methods Four human HCC cell lines representing diverse stages of differentiation were treated with L.obtusiloba extract, standardized according to its known suppressive effects on proliferation and TGF-β-expression. Beside measurement of proliferation, invasion and apoptosis, effects on signal transduction and NF-κB-activity were determined. Results L.obtusiloba extract inhibited proliferation and induced apoptosis in all HCC cell lines and provoked a reduced basal and IGF-1-induced activation of the IGF-1R signaling cascade and a reduced transcriptional NF-κB-activity, particularly in the poorly differentiated SK-Hep1 cells. Pointing to anti-angiogenic effects, L.obtusiloba extract attenuated the basal and IGF-1-induced expression of hypoxia inducible factor-1α, vascular endothelial growth factor, peroxisome proliferator-activated receptor-γ, cyclooxygenase-2 and inducible nitric oxide synthase. Conclusions The traditional application of the extract is confirmed by our experimental data. Due to its potential to inhibit critical receptor tyrosine kinases involved in HCC progression via the IGF-1 signaling pathway and NF-κB, the standardized L.obtusiloba extract should be further analysed for its active compounds and explored as (complementary treatment option for HCC.

  15. Cancer stem cells revisited

    NARCIS (Netherlands)

    Batlle, Eduard; Clevers, Hans

    2017-01-01

    The cancer stem cell (CSC) concept was proposed four decades ago, and states that tumor growth, analogous to the renewal of healthy tissues, is fueled by small numbers of dedicated stem cells. It has gradually become clear that many tumors harbor CSCs in dedicated niches, and yet their

  16. Inflammation and cancer stem cells.

    Science.gov (United States)

    Shigdar, Sarah; Li, Yong; Bhattacharya, Santanu; O'Connor, Michael; Pu, Chunwen; Lin, Jia; Wang, Tao; Xiang, Dongxi; Kong, Lingxue; Wei, Ming Q; Zhu, Yimin; Zhou, Shufeng; Duan, Wei

    2014-04-10

    Cancer stem cells are becoming recognised as being responsible for metastasis and treatment resistance. The complex cellular and molecular network that regulates cancer stem cells and the role that inflammation plays in cancer progression are slowly being elucidated. Cytokines, secreted by tumour associated immune cells, activate the necessary pathways required by cancer stem cells to facilitate cancer stem cells progressing through the epithelial-mesenchymal transition and migrating to distant sites. Once in situ, these cancer stem cells can secrete their own attractants, thus providing an environment whereby these cells can continue to propagate the tumour in a secondary niche. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. Evaluation of chemical composition, antioxidant, antibacterial, cytotoxic and apoptotic effects of Aloysia citrodora extract on colon cancer cell line using Real Time PCR and Flow-cytometry methods

    OpenAIRE

    Amir Mirzaie; Seyed Ataollah Sadat Shandiz; Hassan Noorbazargan; Elahe Ali Asgary

    2016-01-01

    Background and aims: Aloysia citrodora belongs to the Verbenaceae family of plants, a well-known herbal medicine in Iran. The aim of the present study was to investigate the chemical composition, antioxidant, antibacterial, cytotoxic and apoptotic effect of A. citrodora extract against human colon cancer using real time PCR and flow cytometry methods. Materials and Methods: this experimental study was carried out in Islamic Azad University, East Tehran Branch, from March to September of 2...

  18. Antibacterial and anti-breast cancer cell line activities of ...

    African Journals Online (AJOL)

    Purpose: To evaluate the activity of extracts of Sanghuangporus sp.1 fungus against pathogenic bacteria and a breast cancer cell line. Methods: The wild fruiting body and mycelium of Sanghuangporus sp.1 were extracted with water and ethanol by ultrasonication extraction. The activity of the extracts against pathogenic ...

  19. Extracts from New Zealand Undaria pinnatifida Containing Fucoxanthin as Potential Functional Biomaterials against Cancer in Vitro

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    Sheng Kelvin Wang

    2014-03-01

    Full Text Available This study tested extracts from New Zealand seaweed Undaria pinnatifida containing fucoxanthin, in parallel with pure fucoxanthin, in nine human cancer cell lines, for anticancer activity. Growth inhibition effects of extracts from Undaria pinnatifida were found in all types of cancer cell lines in dose- and time- dependent manners. Cytotoxicity of fucoxanthin in three human non-cancer cell lines was also tested. Compared with pure fucoxanthin, our extracts containing low level of fucoxanthin were found to be more effective in inhibiting the growth of lung carcinoma, colon adenocarcinoma and neuroblastoma. Our results suggest that fucoxanthin is a functional biomaterial that may be used as a chemopreventive phytochemical or in combination chemotherapy. Furthermore, we show for the first time that some unknown compounds with potential selective anti-cancer effects may exist in extracts of New Zealand Undaria pinnatifida, and New Zealand Undaria pinnatifida could be used as a source for either functional biomaterial extraction or production of functional food.

  20. The effect of ginger extract on glycoproteins of Raji cells.

    Science.gov (United States)

    Zamani, Zahra; Nassir-Ud-Din; Kohan, Haleemeh Kabini; Kadivar, Mehdi; Kalyee, Zahra; Rad, Behzad Laame; Iravani, Ayda; Rahimi, Nourooz Ali; Wahabi, Farideh; Sadeghi, Sedigheh; Pourfallah, Fatemeh; Arjmand, Mohammad

    2014-01-15

    Protein glycosylation is associated with the development and progression of specific diseases, including cancers. The ginger rhizome is known to have anti-cancer and anti-fungal properties. This investigation was carried out to study the effect of ginger on glycoproteins of Raji cells. A 10% yield of ginger extract was mixed with 0.01% DMSO and added to 6 x 10(4) Raji cells at different concentrations for 24, 48 and 72 h at 37 degrees C. Their half maximal inhibitory concentration (IC50) was determined and analyzed statistically using Graphpad prism software. Cell extracts were prepared and their glycoproteins purified using lectin-affinity chromatography (Q proteome total glycoprotein and O glycoprotein kits) and SDS PAGE was carried out. IC50 of ginger extract on Raji cells was 20 microg mL(-1) at 72 h with < 0.01 significance. Silver staining of purified glycoprotiens in Raji cells indicated the presence of O-glycans and N-glycans. N-linked mannose and N-linked sialic acids were detected with the total glycoprotein kit. O-linked galactose and O-linked sialic acids were identified with the O-glycoprotein. Ginger reduced the expression of O-linked sialic acid and also N-linked mannose on Raji cells but had no effect on other glycoproteins. Sialic acid is now well known as a cancer marker and investigations are on to use it as a drug-target in cancerous tissues.

  1. Cytotoxic Effect of Ethanolic Extract of Sarang Semut (Myrmecodia pendens on HeLa Cervix Cancer Cell Line In Vitro Experimental Study

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    Dina Fatmawati

    2011-12-01

    Design and Method: The method was quasi experimental with post test only non equivalent control group design. HeLa cell was divided into two groups. The first group as positive control with doxorubicin, second group as treatment with ethanolic extract of sarang semut at various concentrations. Ethanolic extract of sarang semut concentrations used were 3,91 μg/ml; 7,81 μg/ml; 15,63 μg/ml; 31,25 μg/ml; 62,50 μg/ml; 125 μg/ml; 250 μg/ml; 500 μg/ml; 1000 μg/ml. Cytotoxic effect was evaluated by direct counting method with tryphan blue dye then using probit regression analysis to find IC50 value. Result: Inhibitory concentration 50 (IC50 value ethanol extract of sarang semut was 33,28 μg/ml. Ethanol extract of sarang semut had a cytotoxicity effect categorized as the moderately active (20 ìg/ml< IC50< 100ìg/ ml. Inhibitory concentration 50 (IC50 value doxorubicin was 5,56 μg/ml. Cytotoxicity effect of doxorubisin higher than cytotoxicity effect of ethanolic extract of sarang semut. Conclusion: Ethanolic extract of sarang semut (Myrmecodia pendens had a cytotoxic effect categorized as the moderately active on HeLa cell (Sains Medika, 3(2:112-120.

  2. Analysis of the Anti-Cancer Effects of Cincau Extract (Premna oblongifolia Merr) and Other Types of Non-Digestible Fibre Using Faecal Fermentation Supernatants and Caco-2 Cells as a Model of the Human Colon

    Science.gov (United States)

    Nurdin, Samsu U.; Le Leu, Richard K.; Young, Graeme P.; Stangoulis, James C. R.; Christophersen, Claus T.; Abbott, Catherine A.

    2017-01-01

    Green cincau (Premna oblongifolia Merr) is an Indonesian food plant with a high dietary fibre content. Research has shown that dietary fibre mixtures may be more beneficial for colorectal cancer prevention than a single dietary fibre type. The aim of this study was to investigate the effects of green cincau extract on short chain fatty acid (SCFA) production in anaerobic batch cultures inoculated with human faecal slurries and to compare these to results obtained using different dietary fibre types (pectin, inulin, and cellulose), singly and in combination. Furthermore, fermentation supernatants (FSs) were evaluated in Caco-2 cells for their effect on cell viability, differentiation, and apoptosis. Cincau increased total SCFA concentration by increasing acetate and propionate, but not butyrate concentration. FSs from all dietary fibre sources, including cincau, reduced Caco-2 cell viability. However, the effects of all FSs on cell viability, cell differentiation, and apoptosis were not simply explainable by their butyrate content. In conclusion, products of fermentation of cincau extracts induced cell death, but further work is required to understand the mechanism of action. This study demonstrates for the first time that this Indonesian traditional source of dietary fibre may be protective against colorectal cancer. PMID:28368356

  3. Analysis of the Anti-Cancer Effects of Cincau Extract (Premna oblongifolia Merr) and Other Types of Non-Digestible Fibre Using Faecal Fermentation Supernatants and Caco-2 Cells as a Model of the Human Colon.

    Science.gov (United States)

    Nurdin, Samsu U; Le Leu, Richard K; Young, Graeme P; Stangoulis, James C R; Christophersen, Claus T; Abbott, Catherine A

    2017-04-03

    Green cincau (Premna oblongifolia Merr) is an Indonesian food plant with a high dietary fibre content. Research has shown that dietary fibre mixtures may be more beneficial for colorectal cancer prevention than a single dietary fibre type. The aim of this study was to investigate the effects of green cincau extract on short chain fatty acid (SCFA) production in anaerobic batch cultures inoculated with human faecal slurries and to compare these to results obtained using different dietary fibre types (pectin, inulin, and cellulose), singly and in combination. Furthermore, fermentation supernatants (FSs) were evaluated in Caco-2 cells for their effect on cell viability, differentiation, and apoptosis. Cincau increased total SCFA concentration by increasing acetate and propionate, but not butyrate concentration. FSs from all dietary fibre sources, including cincau, reduced Caco-2 cell viability. However, the effects of all FSs on cell viability, cell differentiation, and apoptosis were not simply explainable by their butyrate content. In conclusion, products of fermentation of cincau extracts induced cell death, but further work is required to understand the mechanism of action. This study demonstrates for the first time that this Indonesian traditional source of dietary fibre may be protective against colorectal cancer.

  4. Anti-Lung Cancer Activity through Enhancement of Immunomodulation and Induction of Cell Apoptosis of Total Triterpenes Extracted from Ganoderma luncidum (Leyss. ex Fr. Karst.

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    Wei Cao

    2013-08-01

    Full Text Available Ganoderma luncidum (Leyss. ex Fr. Karst. (GLK has been used traditionally for the prevention and treatment of cancers or tumors for a long time in Traditional Chinese Medicine. The triterpenes as main effective components of GLK have been found to be beneficial for the efficacy. The purpose of this study was to examine the anti-lung cancer activity of triterpenes of GLK in vitro and in vivo and to explore their anti-lung cancer effects and potential mechanisms. A549 cells and Lewis tumor-bearing mice were used to evaluate the inhibition effects of triterpenes on cell proliferation and tumor growth. The IC50 of triterpenes of GLK on A549 cells was 24.63 μg/mL. Triterpenes of GLK could significantly inhibit tumor growth in mice (30, 60 and 120 mg/kg. The immune organs indexes including spleen and thymus were increased remarkedly by the treatment with triterpenes. Moreover, they were able to stimulate the immune response by increasing the expressions of IL-6 and TNF-α. Flow cytometric analysis revealed that cell arrest caused by triterpenes treatment (7.5, 15 and 30 μg/mL was in the G2/M phase in A549 cells. Triterpenes induced apoptosis by decreasing the expression of the antiapoptotic protein Bcl-2 and pro-caspase 9 and increasing the levels of cleaved-caspase 9. Our findings suggested that the triterpenes of GLK have anti-lung cancer activity in vitro and in vivo via enhancement of immunomodulation and induction of cell apoptosis. The study provides insights into the mechanism of GLK in the prevention and treatment of lung cancer.

  5. Extraction of soybean oil from single cells.

    Science.gov (United States)

    Kasai, Naoya; Imashiro, Yusuke; Morita, Naofumi

    2003-10-08

    Single cells prepared from autoclaved soybeans and cellulase treatment of the cells were effective in digesting the cell walls of and extracting the oil from soybeans. The first cell wall of the soybean single cell was completely removed using cellulases; the thin and transparent second cell wall of the cell was swollen. Oil in the cell formed spherical or hemispherical oil drops, and oil leaking from the oil bodies was observed. The oil was almost retained within the second cell wall. Water-extractable substances were obtained at approximately >60% of the weight. Flotation of oil drops by centrifugation was easily done. Ambient n-hexane extraction was also possible; however, residual oil remained in the oil bodies. Protease or peptidase digested the structure of the oil bodies; however, separation of the oil and the hydrolysates was impossible. The oil from the oil bodies was obtained effectively (>85%) by pressing the single cells and/or cellulase-treated single cells.

  6. Activations of Both Extrinsic and Intrinsic Pathways in HCT 116 Human Colorectal Cancer Cells Contribute to Apoptosis through p53-Mediated ATM/Fas Signaling by Emilia sonchifolia Extract, a Folklore Medicinal Plant.

    Science.gov (United States)

    Lan, Yu-Hsuan; Chiang, Jo-Hua; Huang, Wen-Wen; Lu, Chi-Cheng; Chung, Jing-Gung; Wu, Tian-Shung; Jhan, Jia-Hua; Lin, Kuei-Li; Pai, Shu-Jen; Chiu, Yu-Jen; Tsuzuki, Minoru; Yang, Jai-Sing

    2012-01-01

    Emilia sonchifolia (L.) DC (Compositae), an herbaceous plant found in Taiwan and India, is used as folk medicine. The clinical applications include inflammation, rheumatism, cough, cuts fever, dysentery, analgesic, and antibacteria. The activities of Emilia sonchifolia extract (ESE) on colorectal cancer cell death have not been fully investigated. The purpose of this study explored the induction of apoptosis and its molecular mechanisms in ESE-treated HCT 116 human colorectal cancer cells in vitro. The methanolic ESE was characterized, and γ-humulene was formed as the major constituent (63.86%). ESE induced cell growth inhibition in a concentration- and time-dependent response by MTT assay. Apoptotic cells (DNA fragmentation, an apoptotic catachrestic) were found after ESE treatment by TUNEL assay and DNA gel electrophoresis. Alternatively, ESE stimulated the activities of caspase-3, -8, and -9 and their specific caspase inhibitors protected against ESE-induced cytotoxicity. ESE promoted the mitochondria-dependent and death-receptor-associated protein levels. Also, ESE increased ROS production and upregulated the levels of ATM, p53, and Fas in HCT 116 cells. Strikingly, p53 siRNA reversed ESE-reduced viability involved in p53-mediated ATM/Fas signaling in HCT 116 cells. In summary, our result is the first report suggesting that ESE may be potentially efficacious in the treatment of colorectal cancer.

  7. Activations of Both Extrinsic and Intrinsic Pathways in HCT 116 Human Colorectal Cancer Cells Contribute to Apoptosis through p53-Mediated ATM/Fas Signaling by Emilia sonchifolia Extract, a Folklore Medicinal Plant

    Directory of Open Access Journals (Sweden)

    Yu-Hsuan Lan

    2012-01-01

    Full Text Available Emilia sonchifolia (L. DC (Compositae, an herbaceous plant found in Taiwan and India, is used as folk medicine. The clinical applications include inflammation, rheumatism, cough, cuts fever, dysentery, analgesic, and antibacteria. The activities of Emilia sonchifolia extract (ESE on colorectal cancer cell death have not been fully investigated. The purpose of this study explored the induction of apoptosis and its molecular mechanisms in ESE-treated HCT 116 human colorectal cancer cells in vitro. The methanolic ESE was characterized, and γ-humulene was formed as the major constituent (63.86%. ESE induced cell growth inhibition in a concentration- and time-dependent response by MTT assay. Apoptotic cells (DNA fragmentation, an apoptotic catachrestic were found after ESE treatment by TUNEL assay and DNA gel electrophoresis. Alternatively, ESE stimulated the activities of caspase-3, -8, and -9 and their specific caspase inhibitors protected against ESE-induced cytotoxicity. ESE promoted the mitochondria-dependent and death-receptor-associated protein levels. Also, ESE increased ROS production and upregulated the levels of ATM, p53, and Fas in HCT 116 cells. Strikingly, p53 siRNA reversed ESE-reduced viability involved in p53-mediated ATM/Fas signaling in HCT 116 cells. In summary, our result is the first report suggesting that ESE may be potentially efficacious in the treatment of colorectal cancer.

  8. Squamous cell skin cancer

    Science.gov (United States)

    ... squamous cell cancer include: Having light-colored skin, blue or green eyes, or blond or red hair Long-term, daily sun exposure (such as in people who work outside) Many severe sunburns early in life Older age Having had many x-rays Chemical exposure A weakened immune system, especially in ...

  9. Cytotoxicity of ethanolic extracts of Artemisia annua to Molt-4 human leukemia cells

    Science.gov (United States)

    Cancer is the second cause of death in the United States, and current treatment is expensive and kills also healthy cells. Affordable alternatives that kill only cancer cells are needed. Artemisinin, extracted from the Artemisia annua, has potent anticancer activity and low toxicity to normal cell...

  10. Algae extracts and methyl jasmonate anti-cancer activities in prostate cancer: choreographers of ‘the dance macabre’

    Directory of Open Access Journals (Sweden)

    Farooqi Ammad Ahmad

    2012-11-01

    Full Text Available Abstract There is an overwhelmingly increasing trend of analysis of naturally occurring ingredients in treatment of prostate cancer. Substantial fraction of information has been added that highlights activity at various levels and steps of deregulated cellular proliferation, metastasis and apoptosis. Among such ingredients, algae extracts and jasmonates are documented to have anti-cancer activity in vitro and in vivo and induce growth inhibition in cancer cells, while leaving the non-transformed cells intact. In this short review we outline systematically, how these ingredients predispose prostate cancer cells to undergo apoptosis.

  11. Modulation of mRNA expression and activities of xenobiotic metabolizing enzymes, CYP1A1, CYP1A2, CYP2E1, GPx and GSTP1 by the Salicornia freitagii extract in HT-29 human colon cancer cells

    Directory of Open Access Journals (Sweden)

    Altay Ahmet

    2017-01-01

    Full Text Available Phase I-II detoxification and antioxidant enzymes are responsible for the detoxification and elimination of activated carcinogens, acting as important biomarkers for chemoprevention. Among them, cytochrome P450s plays a prominent role in the metabolic activation of xenobiotics. The herb Salicornia freitagii (SF (Amaranthaceae is known for its anticancer, antioxidant, antidiabetic and antiinflammatory activities. In this study, we determined the bioactive phenolics in the SF methanol extract and investigated its antiproliferative potential in HT-29 human colon cancer cells. We also investigated the modulation of some phase I and II enzyme (CYP 1A1, 1A2, 2E1, GSTP1 and GPx mRNA expression and enzymatic activities by the SF extract and its major bioactive phenolic compounds. LC/MS-MS analysis showed that the main phenolic compounds of the methanolic SF extract are vanillic acid (48 μg/100g and p-coumaric acid (10.8 μg/100g. SF extract, vanillic acid and p-coumaric acid exhibited high antiproliferative activities in HT-29 cells, with IC50 values of 81.79μg/mL, 98.8 μM and 221.6 μM, respectively. The mRNA expression levels of CYP1A2 and CYP2E1 were decreased, while those of GSTP1 and GPx in HT-29 cells were increased after application of either the SF extract or vanillic acid. The SF extract by itself also increased the activities of GPx and GSTP1 enzymes 1.68- and 1.49-fold, respectively. Our data indicate that the SF extract and its major bioactive compound, vanillic acid, could exert a modulatory effect on the expression of enzymes that are involved in xenobiotic activation and detoxification pathways in the gastrointestinal tract. For this reason, SF can be considered as a natural source of chemopreventive agents.

  12. Fraction against Human Cancer Cell Lines

    African Journals Online (AJOL)

    Purpose: To investigate the anti-proliferative and apoptotic activity of crude and dichloromethane fraction of A. sieberi against seven cancer cell lines (Colo20, HCT116, DLD, MCF7, Jurkat, HepG2 and. L929). Methods: A. sieberi was extracted with methanol and further purification was carried out using liquid-.

  13. Induction of apoptosis by ethanol extract of Citrus unshiu Markovich peel in human bladder cancer T24 cells through ROS-mediated inactivation of the PI3K/Akt pathway.

    Science.gov (United States)

    Ahn, Kyu Im; Choi, Eun Ok; Kwon, Da He; HwangBo, Hyun; Kim, Min Yeong; Kim, Hong Jae; Ji, Seon Yeong; Hong, Su-Hyun; Jeong, Jin-Woo; Park, Cheol; Kim, Nam Deuk; Kim, Wun Jae; Choi, Yung Hyun

    2017-11-20

    Citrus unshiu peel has been used to prevent and treat various diseases in traditional East-Asian medicine including in Korea. Extracts of C. unshiu peel are known to have various pharmacological effects including antioxidant, anti-inflammatory, and antibacterial properties. Although the possibility of their anti-cancer activity has recently been reported, the exact mechanisms in human cancer cells have not been sufficiently studied. In this study, the inhibitory effect of ethanol extract of C. unshiu peel (EECU) on the growth of human bladder cancer T24 cells was evaluated and the underlying mechanism was investigated. The present study demonstrated that the suppression of T24 cell viability by EECU is associated with apoptosis induction. EECU-induced apoptosis was found to correlate with an activation of caspase-8, -9, and -3 in concomitance with a decrease in the expression of the inhibitor of apoptosis family of proteins and an increase in the Bax:Bcl-2 ratio accompanied by the proteolytic degradation of poly(ADP-ribose) polymerase. EECU also increased the generation of reactive oxygen species (ROS), collapse of mitochondrial membrane potential, and cytochrome c release to the cytosol, along with a truncation of Bid. In addition, EECU inactivated phosphatidylinositol 3-kinase (PI3K) as well as Akt, a downstream molecular target of PI3K, and LY294002, a specific PI3K inhibitor significantly enhanced EECU-induced apoptosis and cell viability reduction. However, N-acetyl cysteine, a general ROS scavenger, completely reversed the EECU-induced dephosphorylation of PI3K and Akt, as well as cell apoptosis. Taken together, these findings suggest that EECU inhibits T24 cell proliferation by activating intrinsic and extrinsic apoptosis pathways through a ROS-mediated inactivation of the PI3K/Akt pathway.

  14. Alcohol and Cancer Stem Cells

    OpenAIRE

    Mei Xu; Jia Luo

    2017-01-01

    Heavy alcohol consumption has been associated with increased risk of several cancers, including cancer of the colon, rectum, female breast, oral cavity, pharynx, larynx, liver, and esophagus. It appears that alcohol exposure not only promotes carcinogenesis but also enhances the progression and aggressiveness of existing cancers. The molecular mechanisms underlying alcohol tumor promotion, however, remain unclear. Cancer stem cells (CSC), a subpopulation of cancer cells with self-renewal and ...

  15. Anti-Cancer Effects of Protein Extracts from Calvatia lilacina, Pleurotus ostreatus and Volvariella volvacea

    Directory of Open Access Journals (Sweden)

    Jin-Yi Wu

    2011-01-01

    Full Text Available Calvatia lilacina (CL, Pleurotus ostreatus (PO and Volvariella volvacea (VV are widely distributed worldwide and commonly eaten as mushrooms. In this study, cell viabilities were evaluated for a human colorectal adenocarcinoma cell line (SW480 cells and a human monocytic leukemia cell line (THP-1 cells. Apoptotic mechanisms induced by the protein extracts of PO and VV were evaluated for SW480 cells. The viabilities of THP-1 and SW480 cells decreased in a concentration-dependent manner after 24 h of treatment with the protein extracts of CL, PO or VV. Apoptosis analysis revealed that the percentage of SW480 cells in the SubG1 phase (a marker of apoptosis was increased upon PO and VV protein-extract treatments, indicating that oligonucleosomal DNA fragmentation existed concomitantly with cellular death. The PO and VV protein extracts induced reactive oxygen species (ROS production, glutathione (GSH depletion and mitochondrial transmembrane potential (ΔΨm loss in SW480 cells. Pretreatment with N-acetylcysteine, GSH or cyclosporine A partially prevented the apoptosis induced by PO protein extracts, but not that induced by VV extracts, in SW480 cells. The protein extracts of CL, PO and VV exhibited therapeutic efficacy against human colorectal adenocarcinoma cells and human monocytic leukemia cells. The PO protein extracts induced apoptosis in SW480 cells partially through ROS production, GSH depletion and mitochondrial dysfunction. Therefore, the protein extracts of these mushrooms could be considered an important source of new anti-cancer drugs.

  16. Troubleshooting with cell blanks in PLE extraction.

    Science.gov (United States)

    Fernández-González, V; Grueiro-Noche, G; Concha-Graña, E; Turnes-Carou, M I; Muniategui-Lorenzo, S; López-Mahía, P; Prada-Rodríguez, D

    2005-09-01

    The blank extracts obtained from the pressurized liquid extraction (PLE) of a 11 mL empty cell of ASE 200 were analysed by GC-FID and GC-ECD and many interfering peaks were detected, which could difficult the trace analysis of persistent organic pollutants (i.e. polycyclic aromatic hydrocarbons, aliphatic hydrocarbons and organochlorine pesticides). These interfering compounds were identified as phthalates, silicones and organic acids and their sources were established. A solution to this analytical trouble is a previous extraction step of the empty cell under the same conditions optimised for the sample extraction.

  17. Aqueous Cinnamon Extract (ACE-c from the bark of Cinnamomum cassia causes apoptosis in human cervical cancer cell line (SiHa through loss of mitochondrial membrane potential

    Directory of Open Access Journals (Sweden)

    Chattopadhyay Samit

    2010-05-01

    Full Text Available Abstract Background Chemoprevention, which includes the use of synthetic or natural agents (alone or in combination to block the development of cancer in human beings, is an extremely promising strategy for cancer prevention. Cinnamon is one of the most widely used herbal medicines with diverse biological activities including anti-tumor activity. In the present study, we have reported the anti-neoplastic activity of cinnamon in cervical cancer cell line, SiHa. Methods The aqueous cinnamon extract (ACE-c was analyzed for its cinnamaldehyde content by HPTLC analysis. The polyphenol content of ACE-c was measured by Folin-Ciocalteau method. Cytotoxicity analysis was performed by MTT assay. We studied the effect of cinnamon on growth kinetics by performing growth curve, colony formation and soft agar assays. The cells treated with ACE-c were analyzed for wound healing assay as well as for matrix metalloproteinase-2 (MMP-2 expression at mRNA and protein level by RT-PCR and zymography, respectively. Her-2 protein expression was analyzed in the control and ACE-c treated samples by immunoblotting as well as confocal microscopy. Apoptosis studies and calcium signaling assays were analyzed by FACS. Loss of mitochondrial membrane potential (Δψm in cinnamon treated cells was studied by JC-1 staining and analyzed by confocal microscopy as well as FACS. Results Cinnamon alters the growth kinetics of SiHa cells in a dose-dependent manner. Cells treated with ACE-c exhibited reduced number of colonies compared to the control cells. The treated cells exhibited reduced migration potential that could be explained due to downregulation of MMP-2 expression. Interestingly, the expression of Her-2 oncoprotein was significantly reduced in the presence of ACE-c. Cinnamon extract induced apoptosis in the cervical cancer cells through increase in intracellular calcium signaling as well as loss of mitochondrial membrane potential. Conclusion Cinnamon could be used as a

  18. β-Bisabolene, a Sesquiterpene from the Essential Oil Extract of Opoponax (Commiphora guidottii), Exhibits Cytotoxicity in Breast Cancer Cell Lines.

    Science.gov (United States)

    Yeo, Syn Kok; Ali, Ahmed Y; Hayward, Olivia A; Turnham, Daniel; Jackson, Troy; Bowen, Ifor D; Clarkson, Richard

    2016-03-01

    The essential oils from Commiphora species have for centuries been recognized to possess medicinal properties. Here, we performed gas chromatography-mass spectrometry on the essential oil from opoponax (Commiphora guidotti) and identified bisabolene isomers as the main constituents of this essential oil. Opoponax essential oil, a chemical component; β-bisabolene and an alcoholic analogue, α-bisabolol, were tested for their ability to selectively kill breast cancer cells. Only β-bisabolene, a sesquiterpene constituting 5% of the essential oil, exhibited selective cytotoxic activity for mouse cells (IC50 in normal Eph4: >200 µg/ml, MG1361: 65.49 µg/ml, 4T1: 48.99 µg/ml) and human breast cancer cells (IC50 in normal MCF-10A: 114.3 µg/ml, MCF-7: 66.91 µg/ml, MDA-MB-231: 98.39 µg/ml, SKBR3: 70.62 µg/ml and BT474: 74.3 µg/ml). This loss of viability was because of the induction of apoptosis as shown by Annexin V-propidium iodide and caspase-3/7 activity assay. β-bisabolene was also effective in reducing the growth of transplanted 4T1 mammary tumours in vivo (37.5% reduction in volume by endpoint). In summary, we have identified an anti-cancer agent from the essential oil of opoponax that exhibits specific cytotoxicity to both human and murine mammary tumour cells in vitro and in vivo, and this warrants further investigation into the use of β-bisabolene in the treatment of breast cancers. Copyright © 2015 John Wiley & Sons, Ltd.

  19. Nelumbo nucifera Gaertn leaves extract inhibits the angiogenesis and metastasis of breast cancer cells by downregulation connective tissue growth factor (CTGF) mediated PI3K/AKT/ERK signaling.

    Science.gov (United States)

    Chang, Chun-Hua; Ou, Ting-Tsz; Yang, Mon-Yuan; Huang, Chi-Chou; Wang, Chau-Jong

    2016-07-21

    Nelumbo nucifera Gaertn (Nymphaeaceae) has been recognized as a medicinal plant, which was distributed throughout the Asia. The aqueous extract of Nelumbo nucifera leaves extract (NLE) has various biologically active components such as polyphenols, flavonoids, oligomeric procyanidines. However, the role of NLE in breast cancer therapy is poorly understood. The purpose of this study was to identify the hypothesis that NLE can suppress tumor angiogenesis and metastasis through CTGF (connective tissue growth factor), which has been implicated in tumor angiogenesis and progression in breast cancer MDA-MB-231 cells. We examined the effects of NLE on angiogenesis in the chicken chorioallantoic membrane (CAM) model. The data showed that NLE could reduce the chorionic plexus at day 17 in CAM and the duration of this inhibition was dose-dependent. In Xenograft model, NLE treatment significantly reduced tumor weight and CD31 (capillary density) over control, respectively. We examined the role of angiogenesis involved restructuring of endothelium using human umbilical vein endothelial cell (HUVEC) in Matrigel angiogenesis model. The results indicated that vascular-like structure formation was further blocked by NLE treatment. Moreover, knockdown of CTGF expression markedly reduced the expression of MMP2 as well as VEGF, and attenuated PI3K-AKT-ERK activation, indication that these signaling pathways are crucial in mediating CTGF function. The present results suggest that NLE might be useful for treatment in therapy-resistance triple negative breast cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Characterization and in vitro studies on anticancer, antioxidant activity against colon cancer cell line of gold nanoparticles capped with Cassia tora SM leaf extract

    Science.gov (United States)

    Abel, Ezra Elumalai; John Poonga, Preetam Raj; Panicker, Shirly George

    2016-01-01

    This study was aimed to determine the effectiveness of synthesized gold nanoparticles of an ethnobotanically and medicinally important plant species Cassia tora against colon cancer cells and to find its antibacterial and antioxidant activities. In order to improve the bioavailability of C. tora, we synthesized gold nanoparticles through green synthesis, by simple mixing and stirring of C. tora leaf powder and tetrachloroauric acid (HAuCl4) solution which gave a dispersion of gold nanoparticles conjugate with C. tora secondary metabolites (SMs) with characteristic surface plasmon resonance. It was characterized by Fourier transform infrared spectroscopy, zeta sizer, zeta potential and transmission electron microscopy. Antibacterial activity was carried out for gold nanoparticles conjugated with C. tora SMs, using well-diffusion method. The MTT assay for cell viability and markers such as catalase, nitric oxide and lipid peroxidation was predictable to confirm the cytotoxicity and antioxidant properties. The treatment of gold nanoparticles conjugated with C. tora SMs on Col320 cells showed reduction in the cell viability through MTT assay, and it also significantly suppressed the release of H2O2, LPO and NO production in a dose-dependent manner. C. tora SMs conjugate gold nanoparticles showed enhanced bioavailability, antioxidant and anticancer effect against colon cancer cell line (Col320).

  1. Free amino acid and phenolic contents and antioxidative and cancer cell-inhibiting activities of extracts of 11 greenhouse-grown tomato varieties and 13 tomato-based foods.

    Science.gov (United States)

    Choi, Suk-Hyun; Kim, Hyen-Ryung; Kim, Hyun-Jeong; Lee, In-Seon; Kozukue, Nobuyuki; Levin, Carol E; Friedman, Mendel

    2011-12-28

    Tomato (Solanum lycopersicum) plants synthesize nutrients, pigments, and bioactive compounds that benefit nutrition and human health. The nature and concentrations of these compounds are strongly influenced by varietal factors such as size and color as well as by processing. To better understand how these factors affect the concentration of nutrients and bioactive compounds, we analyzed 11 Korean tomato varieties grown under the same greenhouse conditions and 13 processed commercial tomato products for free amino acids and amino acid metabolites by HPLC, for individual phenolics by HPLC-MS, for total phenolics by the Folin-Ciocalteu method, for antioxidative activity by the FRAP and DPPH methods, and for cancer cell-inhibiting effects by the MTT assay. We also determined the protein content of the tomatoes by an automated Kjeldahl method. The results show that there is a broad range of bioactive compounds across tomato varieties and products. Small tomatoes had higher contents of bioactive compounds than the large ones. The content of phenolic compounds of processed products was lower than that of fresh tomatoes. Tomato extracts promoted growth in normal liver (Chang) cells, had little effect in normal lung (Hel299) cells, mildly inhibited growth of lung cancer (A549) cells, and first promoted and then, at higher concentrations, inhibited growth in lymphoma (U937) cells. The relationship of cell growth to measured constituents was not apparent. Dietary and health aspects of the results are discussed.

  2. Cancer Stem Cells and Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Sheetal Dyall

    2010-01-01

    Full Text Available The cancer stem cell hypothesis is becoming more widely accepted as a model for carcinogenesis. Tumours are heterogeneous both at the molecular and cellular level, containing a small population of cells that possess highly tumourigenic “stem-cell” properties. Cancer stem cells (CSCs, or tumour-initiating cells, have the ability to self-renew, generate xenografts reminiscent of the primary tumour that they were derived from, and are chemoresistant. The characterisation of the CSC population within a tumour that drives its growth could provide novel target therapeutics against these cells specifically, eradicating the cancer completely. There have been several reports describing the isolation of putative cancer stem cell populations in several cancers; however, no defined set of markers has been identified that conclusively characterises “stem-like” cancer cells. This paper highlights the current experimental approaches that have been used in the field and discusses their limitations, with specific emphasis on the identification and characterisation of the CSC population in epithelial ovarian cancer.

  3. Review of procedures used for the extraction of anti-cancer compounds from tropical plants.

    Science.gov (United States)

    Pandey, Saurabh; Shaw, Paul N; Hewavitharana, Amitha K

    2015-01-01

    Tropical plants are important sources of anti-cancer lead molecules. According to the US National Cancer Institute, out of the 3000 plants identified as active against cancer using in vitro studies, 70% are of tropical origin. The extraction of bioactive compounds from the plant materials is a fundamental step whose efficiency is critical for the success of drug discovery efforts. There has been no review published of the extraction procedures of anti-cancer compounds from tropical plants and hence the following is a critical evaluation of such procedures undertaken prior to the use of these compounds in cancer cell line studies, during the last five years. It presents a comprehensive analysis of all approaches taken to extract anti-cancer compounds from various tropical plants. (Databases searched were PubMed, SciFinder, Web of Knowledge, Scopus, Embase and Google Scholar).

  4. The origin of stroma surrounding epithelial ovarian cancer cells.

    Science.gov (United States)

    Akahane, Tomoko; Hirasawa, Akira; Tsuda, Hiroshi; Kataoka, Fumio; Nishimura, Sadako; Tanaka, Hideo; Tominaga, Eiichiro; Nomura, Hiroyuki; Chiyoda, Tatsuyuki; Iguchi, Yoko; Yamagami, Wataru; Susumu, Nobuyuki; Aoki, Daisuke

    2013-01-01

    Cancer stroma is thought to play an important role in tumor behavior, including invasion or metastasis and response to therapy. Cancer stroma is generally thought either to be non-neoplastic cells, including tissue-marrow or bone-marrow-derived fibroblasts, or to originate in epithelial mesenchymal transition of cancer cells. In this study, we evaluated the status of the p53 gene in both the cancer cells and the cancer stroma in epithelial ovarian cancer (EOC) to elucidate the origin of the stroma. Samples from 16 EOC patients were included in this study. Tumor cells and adjacent nontumor stromal cells were microdissected and DNA was extracted separately. We analyzed p53 sequences (exons 5-8) of both cancer and stromal tissues in all cases. Furthermore, we examined p53 protein expression in all cases. Mutations in p53 were detected in 9 of the 16 EOCs: in 8 of these cases, the mutations were detected only in cancer cells. In 1 case, the same mutation (R248Q) was detected in both cancer and stromal tissues, and p53 protein expression was detected in both the cancer cells and the cancer stroma. Most cancer stroma in EOC is thought to originate from non-neoplastic cells, but some parts of the cancer stroma might originate from cancer cells.

  5. Induction of Apoptosis and Reduction of Endogenous Glutathione Level by the Ethyl-Acetate Soluble Fraction of the Methanol Extract of the Roots of Potentilla fulgens in Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Debabrata Tripathy

    Full Text Available Potentilla fulgens root traditionally used as a folk remedy in Meghalaya, India. However, systematic evaluation of its anticancer efficacy was limited. We investigated the anticancer potentials of the various extracts prepared by partitioning of the methanol extract of the root with the aim to discover major contributing factors from the most effective fractions. Methanol extract of P. fulgens roots (PRE was prepared by maceration which was subsequently fractionated into hexane, ethyl-acetate (EA and n-butanol soluble fractions. Various assays (clonogenic assay, Flow cytometry analysis, western blot, semiquantitative RT-PCR and the level of endogenous glutathione were used to evaluate different parameters, such as Cell survivability, PARP-1 proteolysis, expression pattern of anti-apoptotic and γ-glutamyl-cysteine synthetase heavy subunit (GCSC genes in both MCF-7 and U87 cancer cell lines. Since the EA-fraction showed most efficient growth inhibitory effect, it was further purified and a total of nine compounds and some monomeric and dimeric flavan-3-ols were identified and characterized. Three compounds viz., epicatechin (EC, gallic acid (GA and ursolic acid (UA were taken on the basis of their higher yield and 10 μg/ml of each was mixed together. The concentration used in this study for PRE, EA- and Hex-fraction was 100 μg/ml, which was higher than the IC50 value. Apoptotic cell death in the PRE, EA-fraction and EC+GA+UA treated cancer cell cultures was significantly greater than in normal cells due to suppression of anti-apoptotic protein Bcl2 following treatment. Depletion of glutathione by downregulating GCSC was also observed. Induction of apoptosis and lowering the level of glutathione are considered to be positive activity for an anticancer agent. Therefore, modulation of GSH concentration in tumor cells by PRE and its EA-fraction opened up the possibility of a new therapeutic approach because these plant products are not harmful to

  6. Areca nut extracts exert different effects in oral cancer cells depending on serum concentration: A clue to the various oral alterations in betel quid chewers.

    Science.gov (United States)

    Ji, Wen-Tsai; Chuang, Yao-Chi; Chen, Han-Po; Lee, Ching-Chih; Chen, Jeff Yi-Fu; Yang, Sheng-Ru; Chen, Jung-Hua; Wang, Chun-Jen; Chen, Hau-Ren

    2014-01-01

    Betel quid chewing is associated with various pathologic alterations in oral mucosa. However, the molecular mechanism behind so many contradictory alterations remains unclear. Here we aimed to build a model to facilitate the related studies in cultured cells. In our results, areca nut extract (ANE) was found to exert different effects in oral cells depending on the supplemented serum level. ANE strongly induced DNA damage, necrotic ballooning, and inflammatory cytokines under lower serum concentration while might convert to facilitate deregulated growth of serum-supplemented cells via modulating the activity/expression of factors such as E-cadherin and Snail. Despite ANE significantly activated NF-κB, a mediator critical for inflammation, inhibition of NF-κB did not prevent the activation of IL8 promoter. We further discovered Y705-dephosphorylated STAT3 might enhance IL8 transcription. Since necrosis and the inflammatory cytokines could cause massive inflammation, infiltration of interstitial fluid might potentiate cellular resistance against the acute cytotoxicity of ANE and further support the proliferation of transforming cells. Induction of VEGF and angiogenesis under lower serum condition also paved the way for cell growth and subsequent metastasis. Accordingly, we concluded that in correlation with serum infiltration ANE caused particular effects in oral cells and possibly the various clinicopathological alterations in vivo.

  7. Areca nut extracts exert different effects in oral cancer cells depending on serum concentration: A clue to the various oral alterations in betel quid chewers

    Directory of Open Access Journals (Sweden)

    Wen-Tsai Ji

    2014-01-01

    Full Text Available Betel quid chewing is associated with various pathologic alterations in oral mucosa. However, the molecular mechanism behind so many contradictory alterations remains unclear. Here we aimed to build a model to facilitate the related studies in cultured cells. In our results, areca nut extract (ANE was found to exert different effects in oral cells depending on the supplemented serum level. ANE strongly induced DNA damage, necrotic ballooning, and inflammatory cytokines under lower serum concentration while might convert to facilitate deregulated growth of serum-supplemented cells via modulating the activity/expression of factors such as E-cadherin and Snail. Despite ANE significantly activated NF-κB, a mediator critical for inflammation, inhibition of NF-κB did not prevent the activation of IL8 promoter. We further discovered Y705-dephosphorylated STAT3 might enhance IL8 transcription. Since necrosis and the inflammatory cytokines could cause massive inflammation, infiltration of interstitial fluid might potentiate cellular resistance against the acute cytotoxicity of ANE and further support the proliferation of transforming cells. Induction of VEGF and angiogenesis under lower serum condition also paved the way for cell growth and subsequent metastasis. Accordingly, we concluded that in correlation with serum infiltration ANE caused particular effects in oral cells and possibly the various clinicopathological alterations in vivo.

  8. Reactive Oxygen Species-Dependent Apoptosis by Gugulipid Extract of Ayurvedic Medicine Plant Commiphora mukul in Human Prostate Cancer Cells Is Regulated by c-Jun N-Terminal KinaseS⃞

    Science.gov (United States)

    Zeng, Yan; Prakash, Lakshmi; Badmaev, Vladmir; Majeed, Muhammed; Singh, Shivendra V.

    2011-01-01

    Gugulipid (GL), extract of Indian Ayurvedic medicinal plant Commiphora mukul, has been used to treat a variety of ailments. We report an anticancer effect and mechanism of GL against human prostate cancer cells. Treatment with GL significantly inhibited the viability of human prostate cancer cell line LNCaP (androgen-dependent) and its androgen-independent variant (C81) with an IC50 of ∼1 μM (24-h treatment), at pharmacologically relevant concentrations standardized to its major active constituent z-guggulsterone. The GL-induced growth inhibition correlated with apoptosis induction as evidenced by an increase in cytoplasmic histone-associated DNA fragmentation and sub-G0/G1-DNA fraction, and cleavage of poly(ADP-ribose) polymerase. The GL-induced apoptosis was associated with reactive oxygen species (ROS) production and c-Jun NH2-terminal kinase (JNK) activation. The induction of proapoptotic Bcl-2 family proteins Bax and Bak and a decrease of antiapoptotic Bcl-2 protein Bcl-2 were observed in GL-treated cells. SV40 immortalized mouse embryonic fibroblasts derived from Bax-Bak double-knockout mice were significantly more resistant to GL-induced cell killing compared with wild-type cells. It is interesting to note that a representative normal prostate epithelial cell line (PrEC) was relatively more resistant to GL-mediated cellular responses compared with prostate cancer cells. The GL treatment caused the activation of JNK that functioned upstream of Bax activation in apoptosis response. The GL-induced conformational change of Bax and apoptosis were significantly suppressed by genetic suppression of JNK activation. In conclusion, the present study indicates that ROS-dependent apoptosis by GL is regulated by JNK signaling axis. PMID:21115635

  9. Reactive oxygen species-dependent apoptosis by gugulipid extract of Ayurvedic medicine plant Commiphora mukul in human prostate cancer cells is regulated by c-Jun N-terminal kinase.

    Science.gov (United States)

    Xiao, Dong; Zeng, Yan; Prakash, Lakshmi; Badmaev, Vladmir; Majeed, Muhammed; Singh, Shivendra V

    2011-03-01

    Gugulipid (GL), extract of Indian Ayurvedic medicinal plant Commiphora mukul, has been used to treat a variety of ailments. We report an anticancer effect and mechanism of GL against human prostate cancer cells. Treatment with GL significantly inhibited the viability of human prostate cancer cell line LNCaP (androgen-dependent) and its androgen-independent variant (C81) with an IC(50) of ∼1 μM (24-h treatment), at pharmacologically relevant concentrations standardized to its major active constituent z-guggulsterone. The GL-induced growth inhibition correlated with apoptosis induction as evidenced by an increase in cytoplasmic histone-associated DNA fragmentation and sub-G(0)/G(1)-DNA fraction, and cleavage of poly(ADP-ribose) polymerase. The GL-induced apoptosis was associated with reactive oxygen species (ROS) production and c-Jun NH(2)-terminal kinase (JNK) activation. The induction of proapoptotic Bcl-2 family proteins Bax and Bak and a decrease of antiapoptotic Bcl-2 protein Bcl-2 were observed in GL-treated cells. SV40 immortalized mouse embryonic fibroblasts derived from Bax-Bak double-knockout mice were significantly more resistant to GL-induced cell killing compared with wild-type cells. It is interesting to note that a representative normal prostate epithelial cell line (PrEC) was relatively more resistant to GL-mediated cellular responses compared with prostate cancer cells. The GL treatment caused the activation of JNK that functioned upstream of Bax activation in apoptosis response. The GL-induced conformational change of Bax and apoptosis were significantly suppressed by genetic suppression of JNK activation. In conclusion, the present study indicates that ROS-dependent apoptosis by GL is regulated by JNK signaling axis.

  10. Bioconversion of piceid to resveratrol by selected probiotic cell extracts.

    Science.gov (United States)

    Basholli-Salihu, Mimoza; Schuster, Roswitha; Mulla, Dafina; Praznik, Werner; Viernstein, Helmut; Mueller, Monika

    2016-12-01

    Resveratrol exerts several pharmacological activities, including anti-cancer, anti-inflammatory, cardioprotective, or antioxidant effects. However, due to its occurrence in plants more in glycosidic form as piceid, the bioavailability and bioactivity are limited. The enzymatic potential of probiotics for the transformation of piceid to resveratrol was elucidated. Cell extract from Bifidobacteria (B.) infantis, B. bifidum, Lactobacillus (L.) casei, L. plantarum, and L. acidophilus was evaluated for their effect in this bioconversion using high-performance liquid chromatography (HPLC) as analytical tool. Cell extract of B. infantis showed the highest effect on the deglycosylation of piceid to resveratrol, already after 30 min. Cell extracts of all other tested strains showed a significant biotransformation with no further metabolization of resveratrol. The conversion of piceid to resveratrol is of importance to increase bioavailability and bioactivity as shown for anti-inflammation in this study. Cell extracts from probiotics, especially from B. infantis, may be added to piceid containing products, for achieving higher biological effects caused by the bioactivity of resveratrol or by health promoting of the probiotics. These findings open a new perspective of novel combination of cell extracts from probiotics and piceid, in health-promoting pharmaceutical and food products.

  11. Comparison of the effect of chemical composition of anthocyanin-rich plant extracts on colon cancer cell proliferation and their potential mechanism of action using in vitro, in silico, and biochemical assays.

    Science.gov (United States)

    Mazewski, Candice; Liang, Katie; Gonzalez de Mejia, Elvira

    2018-03-01

    The objective was to compare the anti-proliferative effect of anthocyanin-rich plant extracts on human colon cancer cells and determine their mechanism of action. Eleven extracts were tested: red (RG) and purple grape, purple sweet potato, purple carrot, black and purple bean, black lentil (BL), black peanut, sorghum (SH), black rice, and blue wheat. HCT-116 and HT-29 inhibition correlated with total phenolics (r=0.87 and 0.77, respectively), delphinidin-3-O-glucoside concentration with HT-29 inhibition (r=0.69). The concentration inhibition fifty (IC50) for BL, SH, RG on HT-29 and HCT-116 cell proliferation ranged 0.9-2.0mg/mL. Extracts decreased expression of anti-apoptotic proteins (survivin, cIAP-2, XIAP), induced apoptosis, and arrested cells in G1. Anthocyanins exhibited tyrosine kinase inhibitory potential in silico and biochemically; cyanidin-3-O-glucoside had one of the highest binding affinities with all kinases, especially ABL1 (-8.5kcal/mol). Cyanidin-3-O-glucoside and delphinidin-3-O-glucoside inhibited EGFR (IC50=0.10 and 2.37µM, respectively). Cyanidin-3-O-glucoside was the most potent anthocyanin on kinase inhibition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Cancer treatments transform residual cancer cell phenotype

    Directory of Open Access Journals (Sweden)

    Harless William W

    2011-01-01

    Full Text Available Abstract Background Physiologic wound repair and tissue regeneration are associated with distinct cellular behaviors triggered by tissue damage. Normally quiescent stem cells proliferate to regenerate damaged tissue, while relatively immobile epithelial cells can transform into a motile, tissue invasive phenotype through a partial epithelial-mesenchymal transition. These distinct cellular behaviors may have particular relevance to how cancer cells can be predicted to behave after treatments damaging a tumor. Presentation of the hypothesis Surgery, chemotherapy, and radiation therapy trigger highly conserved wound healing pathways that: (1 facilitate the phenotypic transformation of surviving cancer cells into a highly mobile, metastatic phenotype through an EMT or epithelial-mesenchymal transition and (2 induce residual cancer stem cell proliferation. Testing the hypothesis Tissue damage caused by cancer treatments will trigger the release of distinct cytokines with established roles in physiologic wound healing, EMT induction, and stem cell activation. They will be released rapidly after treatment and detectable in the patient's blood. Careful histologic evaluation of cancerous tissue before and after treatment will reveal cellular changes suggestive of EMT induction (down regulation of cytokeratin expression and cancer stem cell enrichment (stem cell markers upregulated. Implications of the hypothesis Cancer cells surviving treatment will be more capable of metastasis and resistant to conventional therapies than the pre-treatment population of cancer cells. These changes will develop rapidly after treatment and, in distinct contrast to selection pressures fostering such changes, be triggered by highly conserved wound repair signals released after tissue damage. This pattern of tissue (tumor repair may be amenable to treatment intervention at the time it is upregulated.

  13. Stem cells and solid cancers.

    Science.gov (United States)

    McDonald, Stuart A C; Graham, Trevor A; Schier, Stefanie; Wright, Nicholas A; Alison, Malcolm R

    2009-07-01

    Recently, there have been significant advances in our knowledge of stem cells found in tissues that can develop solid tumours. In particular, novel stem cell markers have been identified for the first time identifying multipotential cells: a required characteristic of a stem cell. The scarcity of cancer stem cells has been questioned. Current dogma states that they are rare, but novel research has suggested that this may not be the case. Here, we review the latest literature on stem cells, particularly cancer stem cells within solid tumours. We discuss current thinking on how stem cells develop into cancer stem cells and how they protect themselves from doing so and do they express unique markers that can be used to detect stem cells. We attempt to put into perspective these latest advances in stem cell biology and their potential for cancer therapy.

  14. The impact of anticancer activity upon Beta vulgaris extract mediated biosynthesized silver nanoparticles (ag-NPs) against human breast (MCF-7), lung (A549) and pharynx (Hep-2) cancer cell lines.

    Science.gov (United States)

    Venugopal, K; Ahmad, H; Manikandan, E; Thanigai Arul, K; Kavitha, K; Moodley, M K; Rajagopal, K; Balabhaskar, R; Bhaskar, M

    2017-08-01

    The present study tried for a phyto-synthetic method of producing silver nanoparticles (Ag-NPs) with size controlled as and eco-friendly route that can lead to their advanced production with decorative tranquil morphology. By inducing temperature fluctuation of the reaction mixture from 25 to 80°C the plasmon resonance band raised slowly which had an ultimate effect on size and shape of Ag-NPs as shown by UV-visible spectroscopy and TEM results. The biosynthesized nanoparticles showed good cytotoxic impact against MCF-7, A549 and Hep2 cells compared to normal cell lines. Compared to control plates, the percentage of cell growth inhibition was found to be high with as concentrations of Ag-NPs becomes more as determined by MTT assay. The AO/EtBr staining observations demonstrated that the mechanism of cell death induced by Ag-NPs was due to apoptosis in cancer cells. These present results propose that the silver nanoparticles (Ag-NPs) may be utilized as anticancer agents for the treatment of various cancer types. However, there is a need for study of in vivo examination of these nanoparticles to find their role and mechanism inside human body. Further, studies we plan to do biomarker fabrication from the green synthesized plant extract nanoparticles like silver, gold and copper nanoparticles with optimized shape and sizes and their enhancement of these noble nanoparticles. Copyright © 2017. Published by Elsevier B.V.

  15. Cancer stem cells and personalized cancer nanomedicine.

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    Gener, Petra; Rafael, Diana Fernandes de Sousa; Fernández, Yolanda; Ortega, Joan Sayós; Arango, Diego; Abasolo, Ibane; Videira, Mafalda; Schwartz, Simo

    2016-02-01

    Despite the progress in cancer treatment over the past years advanced cancer is still an incurable disease. Special attention is pointed toward cancer stem cell (CSC)-targeted therapies, because this minor cell population is responsible for the treatment resistance, metastatic growth and tumor recurrence. The recently described CSC dynamic phenotype and interconversion model of cancer growth hamper even more the possible success of current cancer treatments in advanced cancer stages. Accordingly, CSCs can be generated through dedifferentiation processes from non-CSCs, in particular, when CSC populations are depleted after treatment. In this context, the use of targeted CSC nanomedicines should be considered as a promising tool to increase CSC sensitivity and efficacy of specific anti-CSC therapies.

  16. Effect of electromagnetic field on okra (Hibiscus sculentus L. developmental stages and the effect of okra extract on breast cancer cells

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    Z. Hasani Sadrabadi

    2016-04-01

    Full Text Available Background and objectives: Electric, magnetic and electromagnetic fields can act as stress factors with different effects on biological systems. Due to the nutritional and medicinal values, and the increasing electromagnetic radiations, the present study was performed to investigate the effects of the electromagnetic field on the developmental stages and cytotoxic properties of okra. Methods: Both dry and wet seeds were exposed to electromagnetic field with the intensities of 2 and 4 mT for 60 minutes. MTT assay was applied to evaluate the potential cytotoxic effects of okra extract on MCF-7 cell line. The anatomical structure of leaves in both treated and untreated (control plants were examined. Results: The results showed that a field intensity of 4 mT increased the speed of germination of wet treated seeds and the stem length of dry treated seeds. MTT assay revealed no cytotoxicity of the aqueous extracts of okra pods up to the concentration of 100 μg/mL from either the treated or the control plants towards the MCF-7 cell line. Conclusion: The results suggest that the electromagnetic fields would be able to increase the speed of germination without effects on percentage of germination.

  17. Toona Sinensis Extracts Induced Cell Cycle Arrest and Apoptosis in the Human Lung Large Cell Carcinoma

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    Cheng-Yuan Wang

    2010-02-01

    Full Text Available Toona sinensis extracts have been shown to exhibit anti-cancer effects in human ovarian cancer cell lines, human promyelocytic leukemia cells and human lung adenocarcinoma. Its safety has also been confirmed in animal studies. However, its anti-cancer properties in human lung large cell carcinoma have not been studied. Here, we used a powder obtained by freeze-drying the super-natant of centrifuged crude extract from Toona sinensis leaves (TSL-1 to treat the human lung carcinoma cell line H661. Cell viability was evaluated by the 3-(4-,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide assay. Flow cytometry analysis revealed that TSL-1 blocked H661 cell cycle progression. Western blot analysis showed decreased expression of cell cycle proteins that promote cell cycle progression, including cyclin-dependent kinase 4 and cyclin D1, and increased the expression of proteins that inhibit cell cycle progression, including p27. Furthermore, flow cytometry analysis showed that TSL-1 induced H661 cell apoptosis. Western blot analysis showed that TSL-1 reduced the expression of the anti-apoptotic protein B-cell lymphoma 2, and degraded the DNA repair protein, poly(ADP-ribose polymerase. TSL-1 shows potential as a novel therapeutic agent or for use as an adjuvant for treating human lung large cell carcinoma.

  18. Cancer stem cells, cancer cell plasticity and radiation therapy.

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    Vlashi, Erina; Pajonk, Frank

    2015-04-01

    Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be eliminated while the survival of differentiated progeny is less critical. In this review we discuss recent reports challenging the idea of a unidirectional differentiation of cancer cells. These reports provide evidence supporting the idea that non-stem cancer cells exhibit a remarkable degree of plasticity that allows them to re-acquire cancer stem cell traits, especially in the context of radiation therapy. We summarize conditions under which differentiation is reversed and discuss the current knowledge of the underlying mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Plant extracts as natural photosensitizers in photodynamic therapy: in vitro activity against human mammary adenocarcinoma MCF-7 cells

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    Rigo Baluyot Villacorta

    2017-04-01

    Conclusions: Two of the plant extracts used, L. racemosa and A. procera were toxic and induced apoptosis to mammary cell adenocarcinoma, MCF-7 when photoactivated. These extracts were also more toxic to human cancer than non-cancer cell lines.

  20. A new prospect in cancer therapy: targeting cancer stem cells to eradicate cancer

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    Chen, Li-Sha; Wang, An-Xin; Dong, Bing; Pu, Ke-Feng; Yuan, Li-Hua; Zhu, Yi-Min

    2012-01-01

    According to the cancer stem cell theory, cancers can be initiated by cancer stem cells. This makes cancer stem cells prime targets for therapeutic intervention. Eradicating cancer stem cells by efficient targeting agents may have the potential to cure cancer. In this review, we summarize recent breakthroughs that have improved our understanding of cancer stem cells, and we discuss the therapeutic strategy of targeting cancer stem cells, a promising future direction for cancer stem cell research. PMID:22507219

  1. Growth Inhibition of Hepatocellular Carcinoma Huh7 Cells by Lactobacillus casei Extract

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    Han, Dae Jong; Kim, Jong Bin; Park, Seo Young; Yang, Man Gil

    2013-01-01

    Purpose Lactobacillus casei (L. casei) is known to exert anti-proliferation effects on many types of cancer cells. However, the effect of L. casei on liver cancer has not been reported. Accordingly, the aim of this study was to determine the anti-cancer effect of L. casei extract on Huh7 cells. Materials and Methods L. casei ATCC393 extract was prepared and purified. After the treatment of L. casei extract on Huh7 cells, cell viability, cell cycle arrest and cell death were analyzed by flow cytometry. The expression levels of tumor necrosis factor-α receptor 1 (TNFR1) and death receptor 3 (DR3) mRNA related with extrinsic apoptosis were assessed by reverse transcription polymerase chain reaction. Additionally, P21 and P27 cell cycle proteins as well as Caspase-3, -8, -9, phospho-Bad and Bcl-2 apoptosis proteins were analyzed by western blot analysis. To determine the effect of L. casei extract on cancer stem-like cells, we analyzed changes in side population fraction through flow cytometry. Results The cell viability of Huh7 cells treated with L. casei extract was decreased by 77%, potentially owing to increases in the rates of Huh7 cells arrested in the G2/M phase (3% increase) and that underwent apoptosis (6% increase). The expression levels of TNFR1 and DR3 mRNA, as well as P21 and P27 cell cycle proteins, were increased. Meanwhile, the expressions of caspase-8, -9, phospho-Bad and Bcl-2 proteins decreased. However, in the case of side population cells, no remarkable changes were observed. Conclusion L. casei extract exerts a potent anti-tumor effect on the viability of liver cancer cells, although not on cancer stem-like cells. PMID:23918568

  2. Anticancer potential of Hericium erinaceus extracts against human gastrointestinal cancers.

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    Li, Guang; Yu, Kai; Li, Fushuang; Xu, Kangping; Li, Jing; He, Shujin; Cao, Shousong; Tan, Guishan

    2014-04-28

    Hericium is a genus of mushrooms (fungus) in the Hericiaceae family. Hericium erinaceus (HE) has been used for the treatment of digestive diseases for over 2000 years in China. HE possesses many beneficial functions such as anticancer, antiulcer, antiinflammation and antimicrobial effects, immunomodulation and other activities. The aim of the studies was to evaluate the anticancer efficacy of two extracts (HTJ5 and HTJ5A) from the culture broth of HE against three gastrointestinal cancers such as liver, colorectal and gastric cancers in both of in vitro of cancer cell lines and in vivo of tumor xenografts and discover the active compounds. Two HE extracts (HTJ5 and HTJ5A) were used for the studies. For the study of chemical constituents, the HTJ5 and HTJ5A were separated using a combination of macroporous resin with silica gel, HW-40 and LH-20 chromatography then purified by semipreparative high-performance liquid chromatography (HPLC) and determined by nuclear magnetic resonance (NMR) spectra. For the in vitro cytotoxicity studies, HepG2 and Huh-7 liver, HT-29 colon, and NCI-87 gastric cancer cell lines were used and MTT assay was performed to determine the in vitro cytotoxicity. For in vivo antitumor efficacy and toxicity studies, tumor xenograft models of SCID mice bearing liver cancer HepG2 and Huh-7, colon cancer HT-29 and gastric cancer NCI-87 subcutaneously were used and the mice were treated with the vehicle control, HTJ5 and HTJ5A orally (500 and 1000 mg/kg/day) and compared to 5-fluorouraci (5-FU) at the maximum tolerated dose (MTD, 25-30 mg/kg/day) intraperitoneally daily for 5 days when the tumors reached about 180-200 mg (mm(3)). Tumor volumes and body weight were measured daily during the first 10 days and 2-3 times a week thereafter to assess the tumor growth inhibition, tumor doubling time, partial and complete tumor response and toxicity. Twenty-two compounds were obtained from the fractions of HTJ5/HTJ5A including seven cycli dipeptides, five

  3. A cell extraction method for oily sediments

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    Michael eLappé

    2011-11-01

    Full Text Available Hydrocarbons can be found in many different habitats and represent an important carbon source for microbes. As fossil fuels, they are also an important economical resource, through natural seepage or accidental release they can also be major pollutants. DNA-specific stains and molecular probes bind to hydrocarbons, causing massive background fluorescence and thereby hampering cell enumeration. The cell extraction procedure of Kallmeyer et al. (2008 separates the cells from the sediment matrix. In principle, this technique can also be used to separate cells from oily sediments, but it is not optimized for this application.Here we present a modified extraction method in which the hydrocarbons are removed prior to cell extraction. Due to the reduced background fluorescence the microscopic image becomes clearer, making cell identification and enumeration much easier. Consequently, the resulting cell counts from samples treated according to our new protocol are significantly higher than those treated according to Kallmeyer et al. (2008. We tested different amounts of a variety of solvents for their ability to remove hydrocarbons and found that n-hexane and – in samples containing more biodegraded oils – methanol, delivered the best results. However, as solvents also tend to lyse cells, it was important to find the optimum solvent to sample ratio, at which hydrocarbon extraction is maximised and cell lysis minimized. A ratio between slurry and solvent of 1:2 to 1:5 delivered the highest cell counts without lysing too many cells. The method provided reproducibly good results on samples from very different environments, both marine and terrestrial.

  4. Apoptosis induced by the methanol extract of Salvia miltiorrhiza Bunge in non-small cell lung cancer through PTEN-mediated inhibition of PI3K/Akt pathway.

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    Ye, Yin-Tao; Zhong, Wei; Sun, Pei; Wang, Dong; Wang, Chen; Hu, Li-Min; Qian, Jun-Qiang

    2017-03-22

    Salvia miltiorrhiza Bunge, a well-known traditional Chinese medicinal (TCM) plant, has been used to treat cardiovascular diseases since thousands of years. Many studies reported that the active component tanshinones displayed a variety of biological activities: anti-thrombous, anti-allergic, anti-inflammatory, antioxidant and anti-tumor promoting. But the mechanism of how the active components working still need to be clarified. The anti-tumor effect of compounds of tanshinone (CTN), the methanol extract of Salvia miltiorrhiza Bunge roots, was investigated. The aim of this study was to investigate the effects of CTN on the growth inhibition, apoptosis and molecular targets of human non-small cell lung cancer (NSCLC). CTN-induced cytotoxicity was determined by MTT assay. The cell survival was evaluated using clonogenic survival assay. The morphology of Glc-82 cells after treatment with CTN was determined by fluorescence microscopy. Cell cycle distribution was revealed by flow cytometry. The apoptotic cells were quantified with annexin V-FITC/PI staining and flow cytometry, and observed using Hoechst 33258 staining and TUNEL assays. The expression levels of proteins were analyzed using western blot. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice. CTN inhibited the proliferation of NSCLC in a dose-dependent manner and induced both early and late apoptosis. Treatment of Glc-82 cells with CTN (5-80μg/ml) significantly (pmethanol extract of Salvia miltiorrhiza Bunge, are the active compounds as shown by their ability to induce apoptosis through the mitochondrial pathway of apoptosis and PTEN-mediated inhibition of PI3K/Akt pathway. CTN could inhibit tumor growth more efficiently, which supports the ethno-medicinal use of this herb as an alternative or complementary therapy for NSCLC. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  5. Anticancer and Anti-Inflammatory Properties of Ganoderma lucidum Extract Effects on Melanoma and Triple-Negative Breast Cancer Treatment.

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    Barbieri, Antonio; Quagliariello, Vincenzo; Del Vecchio, Vitale; Falco, Michela; Luciano, Antonio; Amruthraj, Nagoth Joseph; Nasti, Guglielmo; Ottaiano, Alessandro; Berretta, Massimiliano; Iaffaioli, Rosario Vincenzo; Arra, Claudio

    2017-02-28

    Among the most important traditional medicinal fungi, Ganoderma lucidum has been used as a therapeutic agent for the treatment of numerous diseases, including cancer, in Oriental countries. The aim of this study is to investigate the anti-inflammatory, anticancer and anti-metastatic activities of Ganoderma lucidum extracts in melanoma and triple-negative breast cancer cells. Ganoderma lucidum extracts were prepared by using common organic solvents; MDA-MB 231 and B16-F10 cell lines were adopted as cellular models for triple-negative breast cancer and melanoma and characterized for cell viability, wound-healing assay and measurement of cytokines secreted by cancer cells under pro-inflammatory conditions (incubation with lipopolysaccharide, LPS) and pretreatment with Ganoderma lucidum extract at different concentrations. Our study demonstrates, for the first time, how Ganoderma lucidum extracts can significantly inhibit the release of IL-8, IL-6, MMP-2 and MMP-9 in cancer cells under pro-inflammatory condition. Interestingly, Ganoderma lucidum extracts significantly also decrease the viability of both cancer cells in a time- and concentration-dependent manner, with abilities to reduce cell migration over time, which is correlated with a lower release of matrix metalloproteases. Taken together, these results indicate the possible use of Ganoderma lucidum extract for the therapeutic management of melanoma and human triple-negative breast cancer.

  6. Epigenetics in cancer stem cells.

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    Toh, Tan Boon; Lim, Jhin Jieh; Chow, Edward Kai-Hua

    2017-02-01

    Compelling evidence have demonstrated that bulk tumors can arise from a unique subset of cells commonly termed "cancer stem cells" that has been proposed to be a strong driving force of tumorigenesis and a key mechanism of therapeutic resistance. Recent advances in epigenomics have illuminated key mechanisms by which epigenetic regulation contribute to cancer progression. In this review, we present a discussion of how deregulation of various epigenetic pathways can contribute to cancer initiation and tumorigenesis, particularly with respect to maintenance and survival of cancer stem cells. This information, together with several promising clinical and preclinical trials of epigenetic modulating drugs, offer new possibilities for targeting cancer stem cells as well as improving cancer therapy overall.

  7. Lung cancer - non-small cell

    Science.gov (United States)

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Horn L, Eisenberg R, Gius D, et al. Cancer of the lung. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan ...

  8. From Vegetable Waste to New Agents for Potential Health Applications: Antioxidant Properties and Effects of Extracts, Fractions and Pinocembrin from Glycyrrhiza glabra L. Aerial Parts on Viability of Five Human Cancer Cell Lines.

    Science.gov (United States)

    Aiello, Francesca; Armentano, Biagio; Polerà, Nicoletta; Carullo, Gabriele; Loizzo, Monica Rosa; Bonesi, Marco; Cappello, Maria Stella; Capobianco, Loredana; Tundis, Rosa

    2017-09-13

    Glycyrrhiza glabra cultivation and harvesting produces substantial quantities of aerial parts as waste. With the aim to prospect an innovative valorization of these byproducts, the aerial parts were harvested in May and October and analyzed for their chemical profile, antioxidant properties, and effects on viability of five cancer cell lines. Pinocembrin was the main constituent. A significant protection of lipid peroxidation was observed with the May total extract (IC50 of 4.2 ± 0.4 μg/mL at 30 min of incubation). The effects on viability of HeLa, MCF-7, MDA-MB-231, Caco-2, and PC3 human cancer cells were investigated. All samples shown a remarkable activity with IC50 values below 25 μg/mL. Samples from plants harvested in May exhibited greater activity than those harvested in October. MCF-7 and HeLa were the most sensitive cells with IC50 in the range 2.73-3.01 and 3.28-5.53 μg/mL, respectively. G. glabra aerial parts represent a good source of valuable products.

  9. Cranberry and Grape Seed Extracts Inhibit the Proliferative Phenotype of Oral Squamous Cell Carcinomas

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    Kourt Chatelain

    2011-01-01

    Full Text Available Proanthocyanidins, compounds highly concentrated in dietary fruits, such as cranberries and grapes, demonstrate significant cancer prevention potential against many types of cancer. The objective of this study was to evaluate cranberry and grape seed extracts to quantitate and compare their anti-proliferative effects on the most common type of oral cancer, oral squamous cell carcinoma. Using two well-characterized oral squamous cell carcinoma cell lines, CAL27 and SCC25, assays were performed to evaluate the effects of cranberry and grape seed extract on phenotypic behaviors of these oral cancers. The proliferation of both oral cancer cell lines was significantly inhibited by the administration of cranberry and grape seed extracts, in a dose-dependent manner. In addition, key regulators of apoptosis, caspase-2 and caspase-8, were concomitantly up-regulated by these treatments. However, cranberry and grape seed extracts elicited differential effects on cell adhesion, cell morphology, and cell cycle regulatory pathways. This study represents one of the first comparative investigations of cranberry and grape seed extracts and their anti-proliferative effects on oral cancers. Previous findings using purified proanthocyanidin from grape seed extract demonstrated more prominent growth inhibition, as well as apoptosis-inducing, properties on CAL27 cells. These observations provide evidence that cranberry and grape seed extracts not only inhibit oral cancer proliferation but also that the mechanism of this inhibition may function by triggering key apoptotic regulators in these cell lines. This information will be of benefit to researchers interested in elucidating which dietary components are central to mechanisms involved in the mediation of oral carcinogenesis and progression.

  10. Evaluating the effect of four extracts of avocado fruit on esophageal squamous carcinoma and colon adenocarcinoma cell lines in comparison with peripheral blood mononuclear cells.

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    Vahedi Larijani, Laleh; Ghasemi, Maryam; AbedianKenari, Saeid; Naghshvar, Farshad

    2014-01-01

    Most patients with gastrointestinal cancers refer to the health centers at advanced stages of the disease and conventional treatments are not significantly effective for these patients. Therefore, using modern therapeutic approaches with lower toxicity bring higher chance for successful treatment and reduced adverse effects in such patients. The aim of this study is to evaluate the effect of avocado fruit extracts on inhibition of the growth of cancer cells in comparison with normal cells. In an experimental study, ethanol, chloroform, ethyl acetate, and petroleum extracts of avocado (Persea americana) fruit were prepared. Then, the effects if the extracts on the growth of esophageal squamous cell carcinoma and colon adenocarcinoma cell lines were evaluated in comparison with the control group using the MTT test in the cell culture medium. Effects of the four extracts of avocado fruit on three cells lines of peripheral blood mononuclear cells, esophageal squamous cell carcinoma, and colon adenocarcinoma were tested. The results showed that avocado fruit extract is effective in inhibition of cancer cell growth in comparison with normal cells (PAvocado fruit is rich in phytochemicals, which play an important role in inhibition of growth of cancer cells. The current study for the first time demonstrates the anti-cancer effect of avocado fruit extracts on two cancers common in Iran. Therefore, it is suggested that the fruit extracts can be considered as appropriate complementary treatments in treatment of esophageal and colon cancers.

  11. Grape seed extract targets mitochondrial electron transport chain complex III and induces oxidative and metabolic stress leading to cytoprotective autophagy and apoptotic death in human head and neck cancer cells.

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    Shrotriya, Sangeeta; Deep, Gagan; Lopert, Pamela; Patel, Manisha; Agarwal, Rajesh; Agarwal, Chapla

    2015-12-01

    Head and neck squamous cell carcinoma (HNSCC) is a major killer worldwide and innovative measures are urgently warranted to lower the morbidity and mortality caused by this malignancy. Aberrant redox and metabolic status in HNSCC cells offer a unique opportunity to specifically target cancer cells. Therefore, we investigated the efficacy of grape seed extract (GSE) to target the redox and bioenergetic alterations in HNSCC cells. GSE treatment decreased the mitochondrial electron transport chain complex III activity, increased the mitochondrial superoxide levels and depleted the levels of cellular antioxidant (glutathione), thus resulting in the loss of mitochondrial membrane potential in human HNSCC Detroit 562 and FaDu cells. Polyethylene glycol-SOD addition reversed the GSE-mediated apoptosis without restoring complex III activity. Along with redox changes, GSE inhibited the extracellular acidification rate (representing glycolysis) and oxygen consumption rate (indicating oxidative phosphorylation) leading to metabolic stress in HNSCC cells. Molecular studies revealed that GSE activated AMP-activated protein kinase (AMPK), and suppressed Akt/mTOR/4E-BP1/S6K signaling in both Detroit 562 and FaDu cells. Interestingly, GSE increased the autophagic load specifically in FaDu cells, and autophagy inhibition significantly augmented the apoptosis in these cells. Consistent with in vitro results, in vivo analyses also showed that GSE feeding in nude mice activated AMPK and induced-autophagy in FaDu xenograft tumor tissues. Overall, these findings are innovative as we for the first time showed that GSE targets ETC complex III and induces oxidative and metabolic stress, thereby, causing autophagy and apoptotic death in HNSCC cells. © 2014 Wiley Periodicals, Inc.

  12. Catalytic Therapy of Cancer with Ascorbate and Extracts of Medicinal Herbs

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    Nadejda Rozanova (Torshina

    2010-01-01

    Full Text Available Catalytic therapy (CT is a cancer treatment modality based on the generation of reactive oxygen species (ROS using a combination of substrate molecules and a catalyst. The most frequently used substrate/catalyst pair is ascorbate/Co phthalocyanine (PcCo. In the present work, herb extracts containing pigments have been studied as a catalyst in place of PcCo. Extracts from herbs are expected to have efficiency comparable with that of phthalocyanines but as natural products, to exhibit fewer side effects. The present studies demonstrate that a combined use of ascorbate and herbal extracts results in ROS production and a significant decrease in the number of cancer cells after a single in vitro treatment. Treatment with ascorbate in conjunction with extracts prepared from several medicinal herbs stimulated apoptosis and disrupted the cell cycle. The number of cells accumulating in the sub-G0/G1 stage of the cell cycle was increased 2- to 7-fold, and cells in G2/M increased 1.5- to 20-fold, indicating that the treatment protocol was highly effective in suppressing DNA synthesis and potentially reflecting DNA damage in the tumor cells. In addition, 20–40% of the cells underwent apoptosis within 24 h of completing treatment. Our results suggest that herbal extracts can function as CT catalysts in the treatment of cancer.

  13. Mechanotransduction in cancer stem cells.

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    Hao, Jin; Zhang, Yueling; Ye, Rui; Zheng, Yingcheng; Zhao, Zhihe; Li, Juan

    2013-09-01

    The cancer stem cell (CSC) concept, which arose about a decade ago, proposes that tumor growth is sustained by a subpopulation of highly malignant cells. These cells, termed CSCs, are capable of extensive self-renewal that contributes to metastasis and treatment resistance. Therefore, therapeutic strategies that target CSCs should be developed for improving outcomes of cancer patients. Recent progress has highlighted the importance of physical properties of the extracellular matrix and mechanotransduction pathway in cancer cells during cancer development. On the other hand, the significance of CXCR1, an upstream signal of FAK/PI3K/Akt has been revealed in CSCs. FAK/PI3K/Akt is a key signal mediator in mechanotransduction pathway. Therefore, mechanotransduction could be a new target for CSCs, and would be an innovative way to treat cancer by inhibiting FAK/PI3K/Akt. © 2013 International Federation for Cell Biology.

  14. Ethanol extract of propolis and its constituent caffeic acid phenethyl ester inhibit breast cancer cells proliferation in inflammatory microenvironment by inhibiting TLR4 signal pathway and inducing apoptosis and autophagy.

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    Chang, Huasong; Wang, Yuehua; Yin, Xusheng; Liu, Xinying; Xuan, Hongzhuan

    2017-09-26

    Propolis and its major constituent - caffeic acid phenethyl ester (CAPE) have good abilities on antitumor and anti-inflammation. However, little is known about the actions of propolis and CAPE on tumor in inflammatory microenvironment, and inflammatory responses play decisive roles at different stages of tumor development. To understand the effects and mechanisms of ethanol-extracted Chinese propolis (EECP) and its major constituent - CAPE in inflammation-stimulated tumor, we investigated their effects on Toll-like receptor 4 (TLR4) signaling pathway which plays a crucial role in breast cancer MDA-MB-231 cell line. 80% confluent breast cancer MDA-MB-231 cells were stimulated with 1 μg/mL lipopolysaccaride (LPS). Then the cells were divided for treatment by CAPE (25 μg/mL) and EECP (25, 50 and 100 μg/mL), respectively. Cell viability, nitric oxide (NO) production and cell migration were measured by sulforhodamine B assay, chemical method and scratch assay. The levels of TLR4, MyD88, IRAK4, TRIF, caspase 3, PARP, LC3B and p62 were investigated through western blotting. The expression of TLR4, LC3B and nuclear factor-κB p65 (NF-κB p65) were tested by immunofluorescence microscopy assay. Treatment of different concentrations of EECP (25, 50 and 100 μg/mL) and CAPE (25 μg/mL) significantly inhibited LPS-stimulated MDA-MB-231 cell line proliferation, migration and NO production. Furthermore, EECP and CAPE activated caspase3 and PARP to induce cell apoptosis, and also upregulated LC3-II and decreased p62 level to induce autophagy during the process. TLR4 signaling pathway molecules such as TLR4, MyD88, IRAK4, TRIF and NF-κB p65 were all down-regulated after EECP and CAPE treatment in LPS-stimulated MDA-MB-231 cells. These findings indicated that EECP and its major constituent - CAPE inhibited breast cancer MDA-MB-231 cells proliferation in inflammatory microenvironment through activating apoptosis, autophagy and inhibiting TLR4 signaling pathway. EECP and

  15. Nanotechniques Inactivate Cancer Stem Cells

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    Goltsev, Anatoliy N.; Babenko, Natalya N.; Gaevskaya, Yulia A.; Bondarovich, Nikolay A.; Dubrava, Tatiana G.; Ostankov, Maksim V.; Chelombitko, Olga V.; Malyukin, Yuriy V.; Klochkov, Vladimir K.; Kavok, Nataliya S.

    2017-06-01

    One of the tasks of current oncology is identification of cancer stem cells and search of therapeutic means capable of their specific inhibition. The paper presents the data on phenotype characteristics of Ehrlich carcinoma cells as convenient and easy-to-follow model of tumor growth. The evidence of cancer stem cells as a part of Ehrlich carcinoma and significance of CD44+ and CD44- subpopulations in maintaining the growth of this type of tumor were demonstrated. A high (tenfold) tumorigenic activity of the Ehrlich carcinoma CD44+ cells if compared to CD44- cells was proven. In this pair of comparison, the CD44+ cells had a higher potential of generating in peritoneal cavity of CD44high, CD44+CD24-, CD44+CD24+ cell subpopulations, highlighting the presence of cancer stem cells in a pool of CD44+ cells.

  16. Chemical Characterization and in Vitro Cytotoxicity on Squamous Cell Carcinoma Cells of Carica papaya Leaf Extracts.

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    Nguyen, Thao T; Parat, Marie-Odile; Hodson, Mark P; Pan, Jenny; Shaw, Paul N; Hewavitharana, Amitha K

    2015-12-24

    In traditional medicine, Carica papaya leaf has been used for a wide range of therapeutic applications including skin diseases and cancer. In this study, we investigated the in vitro cytotoxicity of aqueous and ethanolic extracts of Carica papaya leaves on the human oral squamous cell carcinoma SCC25 cell line in parallel with non-cancerous human keratinocyte HaCaT cells. Two out of four extracts showed a significantly selective effect towards the cancer cells and were found to contain high levels of phenolic and flavonoid compounds. The chromatographic and mass spectrometric profiles of the extracts obtained with Ultra High Performance Liquid Chromatography-Quadrupole Time of Flight-Mass Spectrometry were used to tentatively identify the bioactive compounds using comparative analysis. The principal compounds identified were flavonoids or flavonoid glycosides, particularly compounds from the kaempferol and quercetin families, of which several have previously been reported to possess anticancer activities. These results confirm that papaya leaf is a potential source of anticancer compounds and warrant further scientific investigation to validate the traditional use of papaya leaf to treat cancer.

  17. Chemical Characterization and in Vitro Cytotoxicity on Squamous Cell Carcinoma Cells of Carica Papaya Leaf Extracts

    Directory of Open Access Journals (Sweden)

    Thao T. Nguyen

    2015-12-01

    Full Text Available In traditional medicine, Carica papaya leaf has been used for a wide range of therapeutic applications including skin diseases and cancer. In this study, we investigated the in vitro cytotoxicity of aqueous and ethanolic extracts of Carica papaya leaves on the human oral squamous cell carcinoma SCC25 cell line in parallel with non-cancerous human keratinocyte HaCaT cells. Two out of four extracts showed a significantly selective effect towards the cancer cells and were found to contain high levels of phenolic and flavonoid compounds. The chromatographic and mass spectrometric profiles of the extracts obtained with Ultra High Performance Liquid Chromatography-Quadrupole Time of Flight-Mass Spectrometry were used to tentatively identify the bioactive compounds using comparative analysis. The principal compounds identified were flavonoids or flavonoid glycosides, particularly compounds from the kaempferol and quercetin families, of which several have previously been reported to possess anticancer activities. These results confirm that papaya leaf is a potential source of anticancer compounds and warrant further scientific investigation to validate the traditional use of papaya leaf to treat cancer.

  18. Induction of Apoptosis and Cell Cycle Arrest in Human Colorectal Carcinoma by Litchi Seed Extract

    Directory of Open Access Journals (Sweden)

    Chih-Ping Hsu

    2012-01-01

    Full Text Available The Litchi (Litchi chinensis fruit products possess rich amounts of flavanoids and proanthocyanidins. Its pericarp has been shown to inhibit breast and liver cancer cell growth. However, the anticolorectal cancer effect of Litchi seed extract has not yet been reported. In this study, the effects of polyphenol-rich Litchi seed ethanol extract (LCSP on the proliferation, cell cycle, and apoptosis of two colorectal cancer cell lines Colo320DM and SW480 were examined. The results demonstrated that LCSP significantly induced apoptotic cell death in a dose-dependent manner and arrested cell cycle in G2/M in colorectal carcinoma cells. LCSP also suppressed cyclins and elevated the Bax : Bcl-2 ratio and caspase 3 activity. This study provides in vitro evidence that LCSP serves as a potential chemopreventive agent for colorectal cancer.

  19. Cancer stem cell markers in common cancers - therapeutic implications

    DEFF Research Database (Denmark)

    Klonisch, Thomas; Wiechec, Emilia; Hombach-Klonisch, Sabine

    2008-01-01

    Rapid advance in the cancer stem cell field warrants optimism for the development of more reliable cancer therapies within the next 2-3 decades. Below, we characterize and compare the specific markers that are present on stem cells, cancer cells and cancer stem cells (CSC) in selected tissues...

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

    Directory of Open Access Journals (Sweden)

    Abdulrahman Khazim Al-Asmari

    Full Text Available 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

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

    Science.gov (United States)

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

    2015-01-01

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

  2. Syzygium aromaticum extracts as good source of betulinic acid and potential anti-breast cancer

    Directory of Open Access Journals (Sweden)

    Abdalrahim F. A. Aisha

    2011-10-01

    Full Text Available Syzygium aromaticum (L. Merr. & L.M. Perry, Myrtaceae, is an evergreen tree with anticarcinogenic, antimutagenic, aphrodisiac, antimicrobial, antioxidant and antiinflammatory properties. This study aims to investigate the anti-breast cancer effect of extracts from leaves, stem and bark of S. aromaticum and to develop a method for preparation of betulinic acid fraction from the leaves. Betulinic acid, ursolic acid and oleanolic acid contents of the extracts were determined by HPLC. A betulinic acid fraction was pr