Huaier Extract Induces Autophagic Cell Death by Inhibiting the mTOR/S6K Pathway in Breast Cancer Cells
Xiaolong Wang, Wenwen Qi, Yaming Li, Ning Zhang, Lun Dong, Mingjuan Sun, Jinjing Cun, Yan Zhang, Shangge Lv, Qifeng Yang, Xiaolong Wang, Wenwen Qi, Yaming Li, Ning Zhang, Lun Dong, Mingjuan Sun, Jinjing Cun, Yan Zhang, Shangge Lv, Qifeng Yang
Abstract
Huaier extract is attracting increased attention due to its biological activities, including antitumor, anti-parasite and immunomodulatory effects. Here, we investigated the role of autophagy in Huaier-induced cytotoxicity in MDA-MB-231, MDA-MB-468 and MCF7 breast cancer cells. Huaier treatment inhibited cell viability in all three cell lines and induced various large membranous vacuoles in the cytoplasm. In addition, electron microscopy, MDC staining, accumulated expression of autophagy markers and flow cytometry revealed that Huaier extract triggered autophagy. Inhibition of autophagy attenuated Huaier-induced cell death. Furthermore, Huaier extract inhibited the mammalian target of the rapamycin (mTOR)/S6K pathway in breast cancer cells. After implanting MDA-MB-231 cells subcutaneously into the right flank of BALB/c nu/nu mice, Huaier extract induced autophagy and effectively inhibited xenograft tumor growth. This study is the first to show that Huaier-induced cytotoxicity is partially mediated through autophagic cell death in breast cancer cells through suppression of the mTOR/S6K pathway.
Conflict of interest statement
Competing Interests: Huaier extract was kindly provided by Gaitianli Medicine Co., Ltd. (Jiangsu, China). This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.
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References
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