"CCT020312 exerts anti-prostate cancer effect by inducing G1 cell cycle arrest, apoptosis and autophagy through activation of PERK/eIF2α/ATF4/ CHOP signaling"

作者全名："Zhou, Duanfang; Yin, Manjialan; Kang, Baoguo; Yu, Xiaoping; Zeng, Hongfang; Chen, Bo; Wang, Gang; Song, Yi; Liu, Xu; He, Qichen; Wu, Qiuya; Zhang, Limei; Wu, Lihong; Wu, Yuanli; Qu, Na; Li, Xiaoli; Zhou, Weiying"

作者地址："[Zhou, Duanfang; Yin, Manjialan; Yu, Xiaoping; Zeng, Hongfang; Chen, Bo; Wang, Gang; Song, Yi; Liu, Xu; He, Qichen; Wu, Qiuya; Zhang, Limei; Wu, Lihong; Wu, Yuanli; Qu, Na; Li, Xiaoli; Zhou, Weiying] Chongqing Med Univ, Coll Pharm, Dept Pharmacol, Chongqing 400016, Peoples R China; [Zhou, Duanfang; Yin, Manjialan; Yu, Xiaoping; Zeng, Hongfang; Chen, Bo; Wang, Gang; Song, Yi; Liu, Xu; He, Qichen; Wu, Qiuya; Zhang, Limei; Wu, Lihong; Wu, Yuanli; Qu, Na; Li, Xiaoli; Zhou, Weiying] Chongqing Key Lab Drug Metab, Chongqing 400016, Peoples R China; [Zhou, Duanfang; Yin, Manjialan; Yu, Xiaoping; Zeng, Hongfang; Chen, Bo; Wang, Gang; Song, Yi; Liu, Xu; He, Qichen; Wu, Qiuya; Zhang, Limei; Wu, Lihong; Wu, Yuanli; Qu, Na; Li, Xiaoli; Zhou, Weiying] Key Lab Biochem & Mol Pharmacol Chongqing, Chongqing 400016, Peoples R China; [Zhou, Duanfang] Chongqing Med Univ, Dept Pharm, Women & Childrens Hosp, Chongqing 401147, Peoples R China; [Zhou, Duanfang] Chongqing Hlth Ctr Women & Children, Dept Pharm, Chongqing 401147, Peoples R China; [Kang, Baoguo] Liangjiang New Dist Peoples Hosp, Dept Oncol, Chongqing, Peoples R China"

通信作者："Li, XL; Zhou, WY (通讯作者)，Chongqing Med Univ, Coll Pharm, Dept Pharmacol, Chongqing 400016, Peoples R China."

来源：BIOCHEMICAL PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001171257100001

JCR分区：Q1

影响因子：5.3

年份：2024

卷号：221

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：CCT020312; Apoptosis; Autophagy; Prostate cancer; PERK

摘要："PERK/eIF2 alpha/ATF4/CHOP signaling pathway is one of three major branches of unfolded protein response (UPR) and has been implicated in tumor progression. CCT020312 is a selective PERK activator and may have a potential anti-tumor effect. Here we investigated the anti-prostate cancer effect and its underlying mechanism of CCT020312. Our results showed that CCT020312 inhibited prostate cancer cell viability by inducing cell cycle arrest, apoptosis and autophagy through activation of PERK/eIF2 alpha/ATF4/CHOP signaling. CCT020312 treatment caused cell cycle arrest at G1 phase and increased the levels of cleaved-Caspase3, cleaved-PARP and Bax in prostate cancer C4-2 and LNCaP cells. Moreover, CCT020312 increased LC3II/I, Atg12-Atg5 and Beclin1 levels and induced autophagosome formation. Furthermore, knockdown of CHOP reversed CCT020312-induced cell viability decrease, apoptosis and autophagy. Bafilomycin A1 reversed CCT020312-induced cell viability decrease but had no effect on CCT020312-induced CHOP activation in C4-2 and LNCaP cells. In vivo, CCT020312 suppressed tumor growth in C4-2 cells-derived xenograft mouse model, activated PERK pathway, and induced autophagy and apoptosis. Our study illustrates that CCT020312 exerts an anti-tumor effect in prostate cancer via activating the PERK pathway, thus indicating that CCT020312 may be a potential drug for prostate cancer."

基金机构："National Natural Science Foundation of China [81874100, 82373901]; Chongqing Natural Science Foundation Innovation and Development Joint Fund [2022NSCQ-LZX0068]; Innovation research group in Colleges and Universities Program of Chongqing Municipal Education Commission [CXQT20012]; CQMU Program for Youth Innovation in Future Medicine [W0067]; Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0223]"

基金资助正文："This project is supported by grants from National Natural Science Foundation of China (No.81874100 and 82373901) , Chongqing Natural Science Foundation Innovation and Development Joint Fund (2022NSCQ-LZX0068) , Innovation research group in Colleges and Universities Program of Chongqing Municipal Education Commission (No. CXQT20012) , CQMU Program for Youth Innovation in Future Medicine (W0067) , Natural Science Foundation of Chongqing (No. cstc2020jcyj-msxmX0223) ."