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
  • 1. Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou 510006, China. Electronic address: [email protected].
  • 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: [email protected].
  • 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.