Vindoline, a vinca alkaloid derived from Catharanthus roseus, targets ABCB1 to overcome docetaxel resistance in prostate cancer.

Overexpression of ABCB1 is a key driver of docetaxel resistance in prostate cancer, underscoring the urgent requirement for agents that effectively target this transporter. In the present study, vindoline, a vinca alkaloid derived from Catharanthus roseus, was identified as a potent modulator of ABCB1 function. Through the use of network pharmacology, molecular docking and molecular dynamics analyses, vindoline was shown to directly and stably bind to ABCB1. Functional assays demonstrated that vindoline restored docetaxel sensitivity in resistant prostate cancer models both in vitro and in vivo. Mechanistically, vindoline did not alter ABCB1 expression or subcellular localization; however, it did inhibit drug efflux, enhance intracellular drug accumulation, and amplify docetaxel-induced apoptosis and G/M cell cycle arrest. Notably, vindoline exhibited minimal CYP3A4 inhibition and no detectable acute toxicity in vivo. Collectively, these findings establish vindoline as a safe and effective ABCB1-targeting agent with potential to overcome docetaxel resistance in prostate cancer.