Authors
Minna Yao, Wei Zhang, Dong Xu, Likun Ding, Ya Bai, Ruili Li, Kai Gao, Xian Zhao, Huan Dang, Ning Ma, Yuan Li, Weiwei Li, Haifeng Tang, Yi Ding
Published in
European journal of pharmacology. Pages 179340. Sep 10, 2026. Epub Sep 10, 2026.
Abstract
Colorectal cancer (CRC) is a common malignancy with high morbidity and mortality globally. PD16, a novel steroidal saponin from Paris delavayi Franchet, shows cytotoxicity against HepG2 and U87MG cells, but its anti-CRC effects and related molecular mechanisms remain unknown. Our study revealed that PD16 significantly suppressed the growth of HCT116 and HT-29 CRC cells, without noticeable toxic effects on the non-cancerous NCM460 cells. Moreover, PD16 treatment reduced colony formation ability, impaired migration and invasion, and caused arrest of cells predominantly in the G0/G1 phase. PD16 promoted apoptosis, evidenced by elevated expression levels of cleaved caspase-9, cleaved caspase-3, cleaved PARP, and Bax, along with decreased expression of Bcl-2. Mechanistically, PD16 exposure weakened the phosphorylation of AKT and GSK3β. Additionally, combination treatment with the AKT inhibitor MK-2206 enhanced PD16-induced apoptotic effects and further suppressed AKT/GSK3β signaling. Molecular docking demonstrated PD16 had a good binding effect with AKT and GSK3β. In xenograft mouse models, PD16 markedly inhibited CRC tumor growth with concomitant downregulation of the AKT/GSK3β pathway, without major organ toxicity. Collectively, these findings provide the first evidence that PD16 exerts pro-apoptotic effects in CRC cells through the AKT/GSK3β pathway inhibition, thereby confirming it as a valuable novel therapeutic candidate for CRC.
PMID:
42722050
Bibliographic data and abstract were imported from PubMed on 11 Sep 2026.
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