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

Huarong Huang, Ting Liu, Junxi Guo, Lin Yu, Xiaofeng Wu, Yan He, Dongli Li, Junlei Liu, Kun Zhang, Xi Zheng, Susan Goodin

Bioorganic & medicinal chemistry letters 2017 Jun 01

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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. Copyright © 2017 Elsevier Ltd. All rights reserved.

Citation

Huarong Huang, Ting Liu, Junxi Guo, Lin Yu, Xiaofeng Wu, Yan He, Dongli Li, Junlei Liu, Kun Zhang, Xi Zheng, Susan Goodin. Brefeldin A enhances docetaxel-induced growth inhibition and apoptosis in prostate cancer cells in monolayer and 3D cultures. Bioorganic & medicinal chemistry letters. 2017 Jun 01;27(11):2286-2291