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

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

  • Bioorg Med Chem Lett. 2017 Jun 1;27(11):2286-2291. doi: 10.1016/j.bmcl.2017.04.047.
Huarong Huang 1,  Ting Liu 2,  Junxi Guo 2,  Lin Yu 2,  Xiaofeng Wu 2,  Yan He 2,  Dongli Li 3,  Junlei Liu 2,  Kun Zhang 2,  Xi Zheng 4,  Susan Goodin 5
Affiliations

Affiliations

  • 1 Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou 510006, China. Electronic address: hrhuang@gdut.edu.cn.
  • 2 Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou 510006, China.
  • 3 Department of Chemical Engineering and Environment, Wuyi University, Jiangmen 510060, China.
  • 4 Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou 510006, China; Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, United States. Electronic address: xizheng@pharmacy.rutgers.edu.
  • 5 Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, United States.
PMID: 28462831 DOI: 10.1016/j.bmcl.2017.04.047
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.

Keywords

3D culture; Bcl-2; Brefeldin A; Docetaxel; Prostate cancer.

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