CCT020312 exerts anti-prostate cancer effect by inducing G1 cell cycle arrest, apoptosis and autophagy through activation of PERK/eIF2α/ATF4/CHOP signaling
Copyright © 2024 Elsevier Inc. All rights reserved..
PERK/eIF2α/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/eIF2α/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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:221 |
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| Enthalten in: |
Biochemical pharmacology - 221(2024) vom: 29. März, Seite 116038 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Duanfang [VerfasserIn] |
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| Links: |
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| Themen: |
145891-90-3 |
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| Anmerkungen: |
Date Completed 04.03.2024 Date Revised 04.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bcp.2024.116038 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367765578 |
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| 100 | 1 | |a Zhou, Duanfang |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a CCT020312 exerts anti-prostate cancer effect by inducing G1 cell cycle arrest, apoptosis and autophagy through activation of PERK/eIF2α/ATF4/CHOP signaling |
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| 520 | |a Copyright © 2024 Elsevier Inc. All rights reserved. | ||
| 520 | |a PERK/eIF2α/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/eIF2α/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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Autophagy | |
| 650 | 4 | |a CCT020312 | |
| 650 | 4 | |a PERK | |
| 650 | 4 | |a Prostate cancer | |
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| 700 | 1 | |a Kang, Baoguo |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Xiaoping |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Hongfang |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Gang |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xu |e verfasserin |4 aut | |
| 700 | 1 | |a He, Qichen |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Qiuya |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Limei |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Lihong |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yuanli |e verfasserin |4 aut | |
| 700 | 1 | |a Qu, Na |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiaoli |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Weiying |e verfasserin |4 aut | |
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