Manumycin induces apoptosis in prostate cancer cells

Abstract

Jing-Gao Li,1,* Miao-Rong She,2,* Ci-Yong Lu,3 Shan-Shan Wei,2 Ping-Fang Xia,2 Ze-Sheng Lu,2 Qi Peng2 1Department of Nephrology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 2Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 3School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workBackground: Manumycin exhibits an antitumor effect in a variety of cancer cell lines, including prostate cancer cell lines (DU145 and PC-3). Our previous studies demonstrated that manumycin induced the apoptosis of anaplastic thyroid cancer cells and leukemia cells via the intrinsic apoptosis pathway. In the current study, we further evaluated the effect of manumycin in two prostate cancer cell lines (LNCaP and 22Rv1), and here we elucidate some of the underlying mechanisms.Materials and methods: The cell viability of prostate cancer cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay after treatment with manumycin for 48 hours. Apoptosis was detected by flow cytometry using annexin V and propidium iodide. The expressions of B-cell lymphoma (Bcl)-2 family members and the activations of caspase-9 and caspase-3 were detected by Western blotting.Results: Manumycin treatment resulted in significant decreases in the viabilities of the two prostate cancer cell lines in a dose-dependent manner through apoptosis, and this apoptosis involved caspase-9 activation. A specific inhibitor of caspase-9 protected cells from caspase-3 activation, apoptosis, and cytotoxicity induced by manumycin. We also found that manumycin downregulated Bcl-2 expression and upregulated Bax expression.Conclusion: Our data suggest that manumycin induces apoptosis in prostate cancer cells through regulation of the Bcl-2 family involving caspase-9 activation. These results suggest that manumycin may be beneficial for the treatment of prostate cancer.Keyword: Bcl-2, farnesyltransferase inhibitor, caspase-9, caspase-3, Bax