文献类型：期刊文献

英文题名：Marine-derived curdepsidone A inhibits HeLa cell proliferation by modulating ER stress and PERK/ATF4/CHOP pathway

作者：Xu, Sunjie[1];Gong, Lizhi[1];Wang, Wei[1];Ma, Wenxu[2];Xin, Xiujuan[1];Liu, Xigao[3];An, Faliang[1,4]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Mei Long Rd, Shanghai 200237, Peoples R China;[2]Shandong Univ, Cheeloo Coll Med, Sch Publ Hlth, Dept Virol, 44 West Wen Hua Rd, Jinan 250012, Peoples R China;[3]Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Dept Urol, 107 West Wen Hua Rd, Jinan 250012, Peoples R China;[4]Marine Biomed Sci & Technol Innovat Platform Linga, 4,Lane 218,Haiji Sixth Rd, Shanghai 201306, Peoples R China

年份：2026

卷号：1016

外文期刊名：EUROPEAN JOURNAL OF PHARMACOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001681868700001)】；

基金：This study was funded by the Shanghai Natural Science Foundation (25ZR1401076) , the National Key R&D Programme of China (2023YFA0914102) and the National Natural Science Foundation of China (81803391) .

语种：英文

外文关键词：Curdepsidone A; HeLa cells; ER stress; PERK/ATF4/CHOP signaling pathway; IRE1 alpha

摘要：Cervical cancer represents a major malignancy that poses a serious threat to women's health. Curdepsidone A (CDA), a depsidone-type compound isolated from the secondary metabolites of the marine-derived endophytic fungus Curvularia sp. IFB-Z10, has been shown to inhibit the proliferation of cervical cancer HeLa cells and to induce apoptosis. This study aimed to elucidate the key signaling pathways underlying CDA-induced apoptosis in HeLa cells. Omics analysis revealed that CDA affected protein processing in endoplasmic reticulum (ER) in HeLa cells. Western blotting and siRNA-mediated gene silencing revealed that CDA promoted apoptosis by activating the PERK/ATF4/CHOP signaling pathway. Additionally, CDA bound to the kinase domain of IRE1 alpha, inhibited its kinase activity but paradoxically enhanced its RNase activity via allosteric modulation. Furthermore, activation of the ATF6 pathway did not directly contribute to apoptosis. Finally, a xenograft nude mouse model was used to evaluate the in vivo effects and mechanisms of CDA. The results demonstrated that CDA effectively inhibited the proliferation of HeLa cells in vivo and induced apoptosis by upregulating ATF4 levels, consistent with the in vitro findings. In conclusion, our findings indicate that CDA induces sustained ER stress, thereby activating the PERK/ ATF4/CHOP pathway to trigger apoptosis in HeLa cells. Together, these findings define CDA as a novel marine-derived depsidone scaffold that induces apoptosis via sustained ER stress signaling and provides a basis for future structure optimization.