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

  • Biochem Biophys Res Commun. 2026 Jun 18:818:153767. doi: 10.1016/j.bbrc.2026.153767.
Xulong Shao  1 ,  Ruihui Lin  1 ,  Tao Yu  1 ,  Xinyu Hou  1 ,  Yahan Sun  1 ,  Wenchang Cheng  2 ,  Jianying Liu  3 ,  Weiguo Feng  4
Affiliations
  • 1. School of Life Science and Technology, Shandong Second Medical University, Weifang, Shandong, 261053, China.
  • 2. Department of Urology Surgery, Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong, 261000, China. Electronic address: [email protected].
  • 3. Department of Nuclear Medicine, The Third Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, 250031, China. Electronic address: [email protected].
  • 4. School of Life Science and Technology, Shandong Second Medical University, Weifang, Shandong, 261053, China; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA. Electronic address: [email protected].
PMID: 42000630 DOI: 10.1016/j.bbrc.2026.153767
Abstract

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 G2/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.

Keywords
ABCB1; Docetaxel resistance; Prostate cancer; Vindoline.
Products