Brefeldin A enhances docetaxel-induced growth inhibition and apoptosis in prostate cancer cells in monolayer and 3D cultures.

Abstract

Docetaxel is a commonly used chemotherapeutic drug for patients with late stage prostate cancer. However, serious side effect and drug resistance limit its clinical success. Brefeldin A is a 16-membered macrolide antibiotic from mangrove-derived Fungus Aspergillus sp. (9Hu), which exhibited potent cytotoxicity against human cancer cells. In the present study, we determined the effect of brefeldin A on docetaxel-induced growth inhibition and apoptosis in human prostate cancer PC-3 cells. Brefeldin A in combination with docetaxel inhibited the growth of PC-3 cells in monolayer and in three dimensional cultures. The combination also potently stimulated apoptosis in PC-3 cells as determined by propidium iodide staining and morphological assessment. Mechanistic studies showed that growth inhibition and apoptosis in PC-3 cells treated with brefeldin A and docetaxel were associated with decrease in the level of Bcl-2. The present study indicates that combined brefeldin A with docetaxel may represent a novel approach for improving the efficacy of docetaxel, and Bcl-2 may serve as a target for brefeldin A to enhance the effects of docetaxel chemotherapy.

• Authors: Huarong Huang, Ting Liu, Junxi Guo, Lin Yu, Xiaofeng Wu, Yan He, Dongli Li, Junlei Liu, Kun Zhang, Xi Zheng, Susan Goodin
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 27 Issue 11 Pg. 2286-2291 (06 01 2017) ISSN: 1464-3405 [Electronic] England
• PMID: 28462831 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Taxoids
• Docetaxel
• Brefeldin A

Topics

• Apoptosis (drug effects)
• Brefeldin A (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Docetaxel
• Humans
• Male
• Prostatic Neoplasms (pathology)
• Taxoids (pharmacology)