title: Nexrutine inhibits cancer cell growth as a consequence of mitochondrial damage and mitophagy.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wu
authors.forename: Shao-Ming
authors.initials: SM
authors.lastname: Zhou
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Ding
authors.forename: Ying-Ping
authors.initials: YP
authors.lastname: Gong
authors.forename: Weiqi
authors.initials: W
authors.lastname: Zeng
authors.forename: Yi
authors.initials: Y
authors.lastname: Cui
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D063306:Mitophagy / Q000187:drug effects*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C512605:Nexrutine; D010936:Plant Extracts; D005947:Glucose