Ciclopirox Olamine Induces Proliferation Inhibition and Protective Autophagy in Hepatocellular Carcinoma

Abstract

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.

Natural Products as Drug Candidates for Redox-Related Human Disease

“…Wan et al [ 9 ] investigated the repurposing of ciclopirox olamine (CPX), a synthetic antifungal agent for treating tinea corporis, tinea pedis, lichen planus and Candida albicans , to cure hepatocellular carcinoma (HCC). In the study, the researchers identified that CPX (1) inhibited the proliferation of HCC cells by arresting the cell cycle, (2) triggered cellular ROS accumulation as well as the downregulation of DJ-1, an oxidative stress sensor responsible for the onset of oxidative stress-related diseases, for example, cancer, neurodegenerative disorders and type 2 diabetes, (3) promoted complete autophagic flux, and (4) induced glycogen clustering in HCC cells.…”