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CSC-3436 switched tamoxifen-induced autophagy to apoptosis through the inhibition of AMPK/mTOR pathway
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نویسنده
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wu s.-t. ,sun g.-h. ,cha t.-l. ,kao c.-c. ,chang s.-y. ,kuo s.-c. ,way t.-d.
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منبع
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journal of biomedical science - 2016 - دوره : 23 - شماره : 1
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چکیده
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Background: triple-negative breast cancer (tnbc) lacks specific therapeutic target and limits to chemotherapy and is essential to develop novel therapeutic regimens. increasing studies indicated that tamoxifen,a selective estrogen receptor modulators (serms),has anti-tumor therapeutic effect in estrogen receptor α (erα)-negative tumor. here,we determined whether autophagy was activated by tamoxifen in tnbc cells. moreover,csc-3436 displayed strong and selective growth inhibition on cancer cells. next,we investigated the anti-proliferation effect of combination of csc-3436 plus tamoxifen on cell death in tnbc cells. results: our study found that tamoxifen induces autophagy in tnbc cells. endoplasmic reticulum stress and ampk/mtor contributed tamoxifen-induced autophagy. interestingly,in combination treatment with csc-3436 enhanced the anti-proliferative effect of tamoxifen. we found that csc-3436 switched tamoxifen-induced autophagy to apoptosis via cleavage of atg-5. moreover,ampk/mtor pathway may involve in csc-3436 switched tamoxifen-induced autophagy to apoptosis. the combination of tamoxifen and csc-3436 produced stronger tumor growth inhibition compared with csc-3436 or tamoxifen alone treatments in vivo. conclusion: these data indicated that csc-3436 combined with tamoxifen may be a potential approach for treatment tnbc. © 2016 the author(s).
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کلیدواژه
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AMPK/mTOR; CSC-3436; Endoplasmic reticulum stress; Tamoxifen; Triple-negative breast cancer
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آدرس
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division of urology,department of surgery,tri-service general hospital,national defense medical center,taichung, Taiwan, division of urology,department of surgery,tri-service general hospital,national defense medical center,taichung, Taiwan, division of urology,department of surgery,tri-service general hospital,national defense medical center,taichung, Taiwan, division of urology,department of surgery,tri-service general hospital,national defense medical center,taichung, Taiwan, division of urology,department of surgery,tri-service general hospital,national defense medical center,taichung, Taiwan, school of pharmacy,college of pharmacy,china medical university,taichung,taiwan,graduate institute of pharmaceutical chemistry,china medical university,taichung,40402, Taiwan, department of biological science and technology,college of biopharmaceutical and food sciences,china medical university,no. 91 hsueh-shih road,taichung,40402,taiwan,department of health and nutrition biotechnology,college of health science,asia university,taichung, Taiwan
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Authors
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