Ciclopirox Olamine Induces Proliferation Inhibition and Protective Autophagy in Hepatocellular Carcinoma
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...
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MDPI AG
2023-01-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/1/113 |
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| author | Xinyan Wan Junqi Xiang Hui Fan Ying Jiang Yiting Lu Chundong Zhang Ying Zhang Quanmei Chen Yunlong Lei |
| author_facet | Xinyan Wan Junqi Xiang Hui Fan Ying Jiang Yiting Lu Chundong Zhang Ying Zhang Quanmei Chen Yunlong Lei |
| author_sort | Xinyan Wan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T11:28:19Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T11:28:19Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-3c34c769241e4e71b418b196f0567aa32023-11-30T23:55:59ZengMDPI AGPharmaceuticals1424-82472023-01-0116111310.3390/ph16010113Ciclopirox Olamine Induces Proliferation Inhibition and Protective Autophagy in Hepatocellular CarcinomaXinyan Wan0Junqi Xiang1Hui Fan2Ying Jiang3Yiting Lu4Chundong Zhang5Ying Zhang6Quanmei Chen7Yunlong Lei8Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, ChinaDepartment of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, ChinaDepartment of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, ChinaDepartment of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, ChinaDepartment of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, ChinaDepartment of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, ChinaDepartment of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, ChinaDepartment of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, ChinaDepartment of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, ChinaHepatocellular 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.https://www.mdpi.com/1424-8247/16/1/113CPXhepatocellular carcinomaautophagyROS |
| spellingShingle | Xinyan Wan Junqi Xiang Hui Fan Ying Jiang Yiting Lu Chundong Zhang Ying Zhang Quanmei Chen Yunlong Lei Ciclopirox Olamine Induces Proliferation Inhibition and Protective Autophagy in Hepatocellular Carcinoma Pharmaceuticals CPX hepatocellular carcinoma autophagy ROS |
| title | Ciclopirox Olamine Induces Proliferation Inhibition and Protective Autophagy in Hepatocellular Carcinoma |
| title_full | Ciclopirox Olamine Induces Proliferation Inhibition and Protective Autophagy in Hepatocellular Carcinoma |
| title_fullStr | Ciclopirox Olamine Induces Proliferation Inhibition and Protective Autophagy in Hepatocellular Carcinoma |
| title_full_unstemmed | Ciclopirox Olamine Induces Proliferation Inhibition and Protective Autophagy in Hepatocellular Carcinoma |
| title_short | Ciclopirox Olamine Induces Proliferation Inhibition and Protective Autophagy in Hepatocellular Carcinoma |
| title_sort | ciclopirox olamine induces proliferation inhibition and protective autophagy in hepatocellular carcinoma |
| topic | CPX hepatocellular carcinoma autophagy ROS |
| url | https://www.mdpi.com/1424-8247/16/1/113 |
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