@article{Chen2026, 
author = {Chao Chen and Mengqi Wan and Zhixu Zhu and Zhaoyu Xie and Yu Zhang and Tao Xu and Han Meng and Miaomiao Wu and Liangfeng Gui and Hongbo Lv and Guodong Wang and Jun Han and Hui Che},
title = {Ramulus Mori alkaloids (SZ-A) sensitize triple-negative breast cancer to cisplatin via PLA2G2A-mediated ceramide metabolism},
year = {2026},
journal = {Chinese Journal of Natural Medicines},
volume = {24},
number = {8},
pages = {972-986},
keywords = {Ramulus Mori alkaloids, Triple-negative breast cancer (TNBC), Cisplatin, Phospholipase A2 Group IIA (PLA2G2A), Ceramide},
url = {https://www.sciopen.com/article/10.1016/S1875-5364(26)61196-X},
doi = {10.1016/S1875-5364(26)61196-X},
abstract = {Cisplatin (DDP) remains a standard therapy for triple-negative breast cancer (TNBC), yet intrinsic or acquired resistance often limits its efficacy; here, we report that Ramulus Mori alkaloids (SZ-A), an approved botanical α-glucosidase inhibitors, synergize with DDP to suppress TNBC progression in vitro and in vivo by driving PLA2G2A-dependent ceramide accumulation. Combining SZ-A with DDP synergistically inhibits viability, clonogenicity, migration, and invasion, induces S-phase arrest and apoptosis, and attenuates tumor growth in xenograft models. Mechanistically, SZ-A directly binds to and stabilizes PLA2G2A, blocking its autophagic-lysosomal degradation, leading to accumulated PLA2G2A that suppresses fatty acid oxidation and triggers ceramide accrual via ADIPOR2 inhibition. Genetic ablation of PLA2G2A abrogates these effects. DDP further enhances SZ-A-induced PLA2G2A upregulation and ceramide accumulation, resulting amplified cytotoxicity. Our findings reveal SZ-A as a chemosensitizing agent that enhances the efficacy of DDP in TNBC.}
}