title: Apoptotic Effects of Novel Dithiocarbamate Analogs of Emetine in Prostate Cancer Cell Lines.
abstract: OBJECTIVE
  Prostate cancer is one of the leading causes of death in American males. Emetine, a naturally-derived alkaloid from the Ipecacuanha plant, has been shown to have potential for anti-tumorigenic effects for cancer treatments. The objective of this study was to characterize novel emetine dithiocarbamate (EMTDTC) analogs for potent anti-tumorigenic activity with minimal toxicity to normal prostate cells and identify targeted apoptotic regulatory genes. The leading key compounds, EMTDTC-55 and EMTDTC-56 were studied.
  
  
  METHODS
  Established methods of cell flow cytometry were used to analyze apoptotic potential in prostate cancer cell lines (DU145, PC3 and LNCaP) and real time-polymerase chain reaction (PCR) for identifying key genes mediating apoptosis.
  
  
  RESULTS
  The effect of EMTDTC-55 on DU145, LNCaP and PC3 revealed significant anti-tumorigenic activities. Both compounds showed highly significant apoptotic potential on days 3 and 5 in the prostate cancer cells. Key apoptotic genes were differentially regulated suggestive of cell-cycle arrest and apoptotic induction in androgen-independent cell lines, DU145 and PC3, by both compounds. However, in the androgen-dependent cell line LNCaP, cells were marginally affected by EMTDTC-55, but significant apoptosis was observed by EMTDTC-56 leading to cell-cycle arrest.
  
  
  CONCLUSIONS
  Both dithiocarbamate compounds EMTDTC-55 and EMTDTC-56 have significant chemotherapeutic potential in moderately metastatic DU145 and highly metastatic PC3 cells.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics and Child Health, College of Medicine, Howard University, Washington, DC, U.S.A.
authors.forename: Zebalda D
authors.initials: ZD
authors.lastname: Bamji
authors.affiliation: Division of Medical Genetics, Department of Pediatrics and Child Health, College of Medicine, Howard University, Washington, DC, U.S.A.
authors.forename: Kareem N
authors.initials: KN
authors.lastname: Washington
authors.affiliation: Department of Chemistry, Graduate School, Howard University, Washington, D.C, U.S.A.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Akinboye
authors.affiliation: Department of Chemistry, Graduate School, Howard University, Washington, D.C, U.S.A.
authors.forename: Oladapo
authors.initials: O
authors.lastname: Bakare
authors.affiliation: Department of Microbiology, College of Medicine, Howard University, Washington, DC, U.S.A.
authors.forename: Yasmine M
authors.initials: YM
authors.lastname: Kanaan
authors.affiliation: Department of Pharmacology, College of Medicine, Howard University, Washington, DC, U.S.A. rlcopeland@howard.edu.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Copeland
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004050:Ditiocarb / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004640:Emetine / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D004050:Ditiocarb; D004640:Emetine
keywords: Prostate Cancer; apoptosis; chemotherapeutic agents; dithiocarbamate analogs; emetine gene regulation