title: Heat shock protein 90 mediates the apoptosis and autophage in nicotinic-mycoepoxydiene-treated HeLa cells.
abstract: Heat shock protein 90 (Hsp90) is a fascinating target for cancer therapy due to its significant role in the crossroad of multiple signaling pathways associated with cell proliferation and regulation. Hsp90 inhibitors have the potential to be developed into anti-cancer drugs. Here, we identified nicotinic-mycoepoxydiene (NMD), a structurally novel compound as Hsp90 inhibitor to perform the anti-tumor activity. The compound selectively bound to the Hsp90 N-terminal domain, and degraded the Hsp90 client protein Akt. The degradation of Akt detained Bad in non-phosphorylation form. NMD-associated apoptosis was characterized by the formation of fragmented nuclei, poly(ADP-ribose) polymerase cleavage, cytochrome c release, caspase-3 activation, and the increased proportion of sub-G1 phase cells. Interestingly, the apoptosis was accompanied with autophagy, by exhibiting the increased expression of LC-3 and the decrease of lysosome pH value. Our findings provide a novel cellular mechanism by which Hsp90 inhibitor adjusts cell apoptosis and autophagy in vitro, suggesting that NMD not only has a potential to be developed into a novel anti-tumor pharmaceutical, but also exhibits a new mechanism in regulating cancer cell apoptosis and autophagy via Hsp90 inhibition.
authors.affiliation: Key Laboratory for Cell Stress, School of Life Sciences, Xiamen University, Xiamen 361102, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Key Laboratory for Cell Stress, School of Life Sciences, Xiamen University, Xiamen 361102, China.
authors.forename: Shuyan
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Key Laboratory for Cell Stress, School of Life Sciences, Xiamen University, Xiamen 361102, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory for Cell Stress, School of Life Sciences, Xiamen University, Xiamen 361102, China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Wang
authors.affiliation: Key Laboratory for Cell Stress, School of Life Sciences, Xiamen University, Xiamen 361102, China.
authors.forename: Zhonghui
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Key Laboratory for Cell Stress, School of Life Sciences, Xiamen University, Xiamen 361102, China.
authors.forename: Siyang
authors.initials: S
authors.lastname: Song
authors.affiliation: Key Laboratory for Cell Stress, School of Life Sciences, Xiamen University, Xiamen 361102, China ru898@xmu.edu.cn.
authors.forename: Lianru
authors.initials: L
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy / Q000502:physiology*; D001952:Bridged-Ring Compounds / Q000737:chemistry / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D009538:Nicotine / Q000737:chemistry*; D011753:Pyrones / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D001952:Bridged-Ring Compounds; D018841:HSP90 Heat-Shock Proteins; D011753:Pyrones; C476085:mycoepoxydiene; D009538:Nicotine; D002738:Chloroquine; D045304:Cytochromes c
keywords: HeLa cell; apoptosis; autophagy; heat shock protein 90 (Hsp90); inhibitor