2. Academic Validation
  3. ROS generation attenuates the anti-cancer effect of CPX on cervical cancer cells by inducing autophagy and inhibiting glycophagy

ROS generation attenuates the anti-cancer effect of CPX on cervical cancer cells by inducing autophagy and inhibiting glycophagy

  • Redox Biol. 2022 Jul;53:102339. doi: 10.1016/j.redox.2022.102339.
Hui Fan 1,  Yujia He 2,  Junqi Xiang 1,  Jing Zhou 3,  Xinyan Wan 1,  Jiawei You 4,  Kailong Du 1,  Yue Li 1,  Lin Cui 1,  Yitao Wang 1,  Chundong Zhang 1,  Youquan Bu 1,  Yunlong Lei 5
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, and Molecular Medicine and Cancer Research Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China.
  • 2 Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, 610041, PR China; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, PR China.
  • 3 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, PR China.
  • 4 Department of Basic Medicine, and Molecular Medicine and Cancer Research Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China.
  • 5 Department of Biochemistry and Molecular Biology, and Molecular Medicine and Cancer Research Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China. Electronic address: leiyunglong@cqmu.edu.cn.
PMID: 35636017 DOI: 10.1016/j.redox.2022.102339
Abstract

Cervical Cancer is one of the most common gynecological malignancies with poor prognosis due to constant chemoresistance and repeated relapse. Ciclopirox olamine (CPX), a synthetic Antifungal agent, has recently been identified to be a promising anti-cancer candidate. However, the detailed mechanisms related to its anti-cancer effects remain unclear and need to be further elucidated. In this study, we found that CPX could induce proliferation inhibition in cervical Cancer cells by targeting PARK7. Further results demonstrated that CPX could induce cytoprotective Autophagy by downregulating the expression of PARK7 to activate PRKAA1 or by PARK7-independent accumulation of ROS to inhibit mTOR signaling. Meanwhile, CPX treatment increased the glycogen clustering and glycophagy in cervical Cancer cells. The presence of N-acetyl-l-cysteine (NAC), a ROS scavenger, led to further clustering of glycogen in cells by reducing Autophagy and enhancing glycophagy, which promoted CPX-induced inhibition of cervical Cancer cell proliferation. Together, our study provides new insights into the molecular mechanisms of CPX in the anti-cancer therapy and opens new avenues for the glycophagy in Cancer therapeutics.

Keywords

CPX; Cervical cancer; Glycophagy; PARK7/DJ-1; ROS.

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