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

作者全名："Fan, Hui; He, Yujia; Xiang, Junqi; Zhou, Jing; Wan, Xinyan; You, Jiawei; Du, Kailong; Li, Yue; Cui, Lin; Wang, Yitao; Zhang, Chundong; Bu, Youquan; Lei, Yunlong"

作者地址："[Fan, Hui; Xiang, Junqi; Wan, Xinyan; Du, Kailong; Li, Yue; Cui, Lin; Wang, Yitao; Zhang, Chundong; Bu, Youquan; Lei, Yunlong] Chongqing Med Univ, Dept Biochem & Mol Biol, Mol Med, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China; [He, Yujia] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Lab Med, Chengdu 610041, Peoples R China; [He, Yujia; Zhou, Jing] Sichuan Univ, State Key Lab Biotherapy, Chengdu 610041, Peoples R China; [You, Jiawei] Chongqing Med Univ, Dept Basic Med, Mol Med, Dept Basic Med, Chongqing 400016, Peoples R China; [Fan, Hui; He, Yujia; Xiang, Junqi; Zhou, Jing; Wan, Xinyan; You, Jiawei; Du, Kailong; Li, Yue; Cui, Lin; Wang, Yitao; Zhang, Chundong; Bu, Youquan; Lei, Yunlong] Chongqing Med Univ, Coll Basic Med Sci, Canc Res Ctr, Chongqing 400016, Peoples R China; [He, Yujia; Zhou, Jing] Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Chengdu 610041, Peoples R China; [He, Yujia; Zhou, Jing] Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Peoples R China; [He, Yujia; Zhou, Jing] Sichuan Univ, West China Hosp, Canc Ctr, Chengdu 610041, Peoples R China"

通信作者："Lei, YL (通讯作者)，Chongqing Med Univ, Dept Biochem & Mol Biol, Mol Med, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China.; Lei, YL (通讯作者)，Chongqing Med Univ, Coll Basic Med Sci, Canc Res Ctr, Chongqing 400016, Peoples R China."

来源：REDOX BIOLOGY

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000808462200002

JCR分区：Q1

影响因子：11.4

年份：2022

卷号：53

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：CPX; Cervical cancer; Glycophagy; PARK7; DJ-1; ROS

摘要："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 PARK7independent 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."

基金机构：Chinese NSFC [81872014]; Chongqing Natural Science Foundation [cstc2016jcyjA0227]; CQMU Program for Youth Innovation in Future Medicine [W0089]; Chongqing Medical University Graduate Talent Training Program [BJRC202120]

基金资助正文："Acknowledgements This work was supported by grants from Chinese NSFC (81872014) , Chongqing Natural Science Foundation (cstc2016jcyjA0227) , CQMU Program for Youth Innovation in Future Medicine (W0089) , and Chongqing Medical University Graduate Talent Training Program (BJRC202120) ."