A novel role for ketoconazole in hepatocellular carcinoma treatment: linking PTGS2 to mitophagy machinery

被引：26
作者：
Chen, Hai-Ning [1 ,2 ]
Chen, Yan [3 ,4 ,5 ,6 ]
Zhou, Zong-Guang [1 ,2 ]
Wei, Yuquan [3 ,4 ,5 ,6 ]
Huang, Canhua [3 ,4 ,5 ,6 ]
机构：
[1] Sichuan Univ, Collaborat Innovat Ctr Biotherapy, West China Hosp, Dept Gastrointestinal Surg,State Key Lab Biothera, Chengdu, Sichuan, Peoples R China
[2] Sichuan Univ, Collaborat Innovat Ctr Biotherapy, West China Hosp, Ctr Canc, Chengdu, Sichuan, Peoples R China
[3] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Dept Biotherapy, Chengdu 610041, Sichuan, Peoples R China
[4] Sichuan Univ, West China Hosp, Ctr Canc, Chengdu 610041, Sichuan, Peoples R China
[5] Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Chengdu 610041, Sichuan, Peoples R China
[6] Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Sichuan, Peoples R China
来源：
AUTOPHAGY | 2019年 / 15卷 / 04期
基金：
中国国家自然科学基金;
关键词：
Apoptosis; hepatocellular carcinoma; ketoconazole; mitophagy; PTGS2;
D O I：
10.1080/15548627.2019.1569934
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Ketoconazole is a broad-spectrum antifungal agent, which has recently been characterized as a potential anticancer agent in several cancer types. However, the molecular mechanism underlying the anticancer effect of ketoconazole is not clearly defined. Our recent findings demonstrate that ketoconazole suppresses the growth of hepatocellular carcinoma (HCC) cells by exacerbating mitophagy in vitro and in vivo. Mechanistically, PINK1-PRKN-mediated mitophagy are led by ketoconazole-induced suppression of PTGS2 (prostaglandin-endoperoxide synthase 2), which in turn results in mitochondrial dysfunction and consequent apoptosis. These data link PTGS2 to mitophagy machinery and implicate ketoconazole as a potential therapeutic option for HCC treatment.
引用
收藏
页码：733 / 734
页数：2
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