Nexrutine inhibits cancer cell growth as a consequence of mitochondrial damage and mitophagy.
Ключові слова
Анотація
OBJECTIVE
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.
CONCLUSIONS
Our study revealed that autophagy plays an important role in the inhibition of cancer cell proliferation by Nexrutine.
