Nexrutine inhibits cancer cell growth as a consequence of mitochondrial damage and mitophagy.

Abstract

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.

• Authors: Xiang Wu, Shao-Ming Zhou, Yi-Ling Ding, Ying-Ping Gong, Weiqi Zeng, Yi Cui
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 36 Issue 2 Pg. 763-72 ( 2015) ISSN: 1421-9778 [Electronic] Germany
• PMID: 26021264 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 S. Karger AG, Basel.

Chemical References

• Antineoplastic Agents, Phytogenic
• Nexrutine
• Plant Extracts
• Glucose

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Autophagy (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Glucose (metabolism)
• Humans
• Male
• Mitochondria (drug effects, metabolism, pathology)
• Mitophagy (drug effects)
• Neoplasms (drug therapy, metabolism, pathology)
• Plant Extracts (pharmacology)