Ciclopirox Olamine Induces Proliferation Inhibition and Protective Autophagy in Hepatocellular Carcinoma
作者全名："Wan, Xinyan; Xiang, Junqi; Fan, Hui; Jiang, Ying; Lu, Yiting; Zhang, Chundong; Zhang, Ying; Chen, Quanmei; Lei, Yunlong"
作者地址："[Wan, Xinyan; Xiang, Junqi; Fan, Hui; Jiang, Ying; Lu, Yiting; Zhang, Chundong; Zhang, Ying; Chen, Quanmei; Lei, Yunlong] Chongqing Med Univ, Coll Basic Med Sci, Mol Med & Canc Res Ctr, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China"
通信作者："Chen, QM; Lei, YL (通讯作者)，Chongqing Med Univ, Coll Basic Med Sci, Mol Med & Canc Res Ctr, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China."
关键词：CPX; hepatocellular carcinoma; autophagy; ROS
摘要："Hepatocellular carcinoma is one of the most common fatal malignancies worldwide. Thus far, the hepatocellular carcinoma prognosis has been bleak due to deficiencies in the identification and diagnosis of early hepatocellular carcinoma. Ciclopirox olamine (CPX) is a synthetic antifungal agent and has been considered as an anti-cancer candidate drug recently, though the detailed mechanisms related to its anti-cancer effect in hepatocellular carcinoma have not yet been revealed. Here, we found that CPX could inhibit proliferation in HCC cells but not in intrahepatic cholangiocarcinoma cells by arresting the cell cycle. Moreover, the anti-cancer effects of CPX in HCC cells were also attributed to CPX-triggered ROS accumulation and DJ-1 downregulation. Additionally, CPX could promote complete autophagic flux, which alleviated the anti-cancer effect of CPX in HCC cells, whereas the ROS scavenger (NAC) would attenuate CPX-induced protective autophagy. Interestingly, CPX could also induce glycogen clustering in HCC cells. Altogether, this study provides a new insight into the detailed molecular mechanisms of CPX as an anti-cancer therapy and a strategy for treating hepatocellular carcinoma."
基金机构：Basic Sciences and Advanced Technology Key Project of CQ CSTC [cstc2017jcyjBX0069]; CQMU Program for Youth Innovation in Future Medicine [W0089]; Chongqing Medical University Graduate Talent Training Program [BJRC202122]
基金资助正文："This work was supported by grants from the Basic Sciences and Advanced Technology Key Project of CQ CSTC (No. cstc2017jcyjBX0069), CQMU Program for Youth Innovation in Future Medicine (W0089), and Chongqing Medical University Graduate Talent Training Program (BJRC202122)."