Heat shock protein 90 mediates the apoptosis and autophage in nicotinic-mycoepoxydienetreated HeLa cells

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 nico...

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Bibliographic Details
Published in生物化学与生物物理学报：英文版 no. 6; pp. 451 - 458
Main Author Yifei Sun Shuyan Xiao Junjie Chen Miaomiao Wang Zhonghui Zheng Siyang Song Lianru Zhang
Format Journal Article
LanguageEnglish
Published 01.06.2015
Subjects
caspase-3
HeLa细胞
HSP90
烟碱
热休克蛋白90
细胞凋亡
自噬
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Summary: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 antitumor 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.
Bibliography:31-1940/Q
heat shock protein 90 （Hsp90）, inhibitor, apoptosis, autophagy, HeLa ce
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 antitumor 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.
ISSN:1672-9145
1745-7270