title: Manumycin induces apoptosis in prostate cancer cells.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nephrology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, China.
authors.forename: Jing-Gao
authors.initials: JG
authors.lastname: Li
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, China.
authors.forename: Miao-Rong
authors.initials: MR
authors.lastname: She
authors.affiliation: School of Public Health, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Ci-Yong
authors.initials: CY
authors.lastname: Lu
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Wei
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, China.
authors.forename: Ping-Fang
authors.initials: PF
authors.lastname: Xia
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, China.
authors.forename: Ze-Sheng
authors.initials: ZS
authors.lastname: Lu
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Peng
keywords: Bax; Bcl-2; caspase-3; caspase-9; farnesyltransferase inhibitor