Guangsangon E triggers mitochondria dysfunction and mitophagy in triple-negative breast cancer and leads to non-apoptotic cell death

广三功 E 引发三阴性乳腺癌中的线粒体功能障碍和线粒体自噬,并导致非凋亡性细胞死亡

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作者:Yuhang Shen, Zhuo Han, Luping Wang, Yan Liang, Xiaoyong Zhang, Wei Li, Shouxin Li, Jingkui Tian, Haote Han

Abstract

Guangsangon E (GSE) is a natural product separated from Morus alba L. It has been reported to treat lung cancer through autophagy. However, whether GSE is effective in repressing triple-negative breast cancer (TNBC) cells is yet to be elucidated. In the present study, GSE inhibited cell growth of MDA-MB-231, MDA-MB-453, and MDA-MB-468 cells. Moreover, GSE induced mitochondrial dysfunction, including membrane potential loss, mitochondria fission, and reactive oxygen species accumulation, and finally led to mitophagy-related non-apoptotic cell death. In the xenograft tumor nude mice, GSE treatment significantly reduced the size and weight of MDA-MB-231 tumors. The tumor inhibition rates of GSE treatment were 49.68% (low-dose) and 48.73% (high-dose). In summary, GSE is a potential anticancer drug available for treating TNBC with apoptosis resistance.

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