“Molecular insights into the synergistic anticancer effect of stigmasterol and cabazitaxel in colon cancer through ROS-mediated mitochondrial dysfunction and apoptosis”

This study examines the combined use of cabazitaxel (CBT) and stigmasterol (STR) to overcome chemotherapy limitations such as drug resistance and toxicity. The combination demonstrates significant synergistic tumor-inhibitory effects and may represent an improved treatment strategy for colon cancer therapy. CBT/STR co-treatment was assessed in HCT116 cells using assays for cell viability, apoptosis, oxidative stress, and cell cycle analysis. The mechanistic findings were supported by western blot analysis of key apoptotic and anti-apoptotic proteins, validation in 3D spheroid model and molecular docking to evaluate apoptosis-related molecular interaction. CBT/STR synergistically inhibited colon cancer cell growth which was associated with ROS-mediated mitochondrial dysfunction, G1 cell cycle arrest and activation of the intrinsic apoptotic pathway. These effects were further supported by tumor growth suppression in 3D spheroid models while molecular docking studies predicted favourable interaction with apoptosis-related proteins. Our study highlights that STR amplifies the anti-tumor effects against colon cancer and may represent a promising therapeutic approach that warrants further validation in in vivo studies.