ASIA unversity:Item 310904400/108423
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    题名: CSC-3436 switched tamoxifen-induced autophagy to apoptosis through the inhibition of AMPK/mTOR pathway
    作者: Way, 魏宗德；Tzong-Der Way；Guang-Huan S；Guang-Huan Sun；Tai-Lung Cha；Tai-Lung Cha；Chien-Chang；Chien-Chang Kao；Sun-Yran Cha；Sun-Yran Chang；Sheng-Chu Ku；Sheng-Chu Kuo；魏宗德；Tzong-Der
    贡献者: 保健營養生技學系
    日期: 2017
    上传时间: 2017-12-08 06:12:14 (UTC+0)
    摘要: 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.
    關聯: JOURNAL OF BIOMEDICAL SCIENCE
    显示于类别:[食品營養與保健生技學系] 期刊論文

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