Nexrutine Inhibits Cancer Cell Growth as a Consequence of Mitochondrial Damage and Mitophagy

作者：Wu, Xiang; Zhou, Shao-ming; Ding, Yi-Ling^*; Gong, Ying-ping; Zeng, Weiqi; Cui, Yi

来源：Cellular Physiology and Biochemistry, 2015, 36(2): 763-772.

DOI：10.1159/000430136

• Nexrutine
• Autophagy
• Mitophagy
• p21
• p27

Background/Aims: Nexrutine is an herbal extract of Phellodendron amurense and has been used as nutrient supplement in China as well as America. Potential protection effect of Nexrutine has been reported. Methods: To investigate the mechanism of Nexrutine, we used the HeLa, U2OS and HCT116 as a model. Based on the acidification of cell culture media, we examined the lactate, mitochondria damage as well as mitophagy status by corresponding assay. Results: Our data suggest that Nexrutine alters the cellular glucose metabolism to promote lactate production. This effect is caused by mitochondrial damage, not an alteration to lactate dehydrogenase activity. As a result of the mitochondrial damage, cell proliferation was inhibited and was associated with an elevation in p21/p27 proteins, which are both important cell cycle inhibitors. As another consequence of the mitochondrial damage, mitophagy was highly activated in Nexrutine-treated cells in a dose-dependent manner. When the autophagy pathway was blocked by siRNAs against BECN1 or ATG7, the growth inhibition caused by Nexrutine was reversed. Conclusion: Our study revealed that autophagy plays an important role in the inhibition of cancer cell proliferation by Nexrutine.

• 出版日期2015-5
• 单位中南大学