PMID- 26254362 OWN - NLM STAT- MEDLINE DCOM- 20160428 LR - 20150808 IS - 1791-7530 (Electronic) IS - 0250-7005 (Linking) VI - 35 IP - 9 DP - 2015 Sep TI - Apoptotic Effects of Novel Dithiocarbamate Analogs of Emetine in Prostate Cancer Cell Lines. PG - 4723-32 AB - BACKGROUND/AIM: 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. MATERIALS AND 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. CONCLUSION: Both dithiocarbamate compounds EMTDTC-55 and EMTDTC-56 have significant chemotherapeutic potential in moderately metastatic DU145 and highly metastatic PC3 cells. CI - Copyright(c) 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved. FAU - Bamji, Zebalda D AU - Bamji ZD AD - Division of Medical Genetics, Department of Pediatrics and Child Health, College of Medicine, Howard University, Washington, DC, U.S.A. FAU - Washington, Kareem N AU - Washington KN AD - Division of Medical Genetics, Department of Pediatrics and Child Health, College of Medicine, Howard University, Washington, DC, U.S.A. FAU - Akinboye, Emmanuel AU - Akinboye E AD - Department of Chemistry, Graduate School, Howard University, Washington, D.C, U.S.A. FAU - Bakare, Oladapo AU - Bakare O AD - Department of Chemistry, Graduate School, Howard University, Washington, D.C, U.S.A. FAU - Kanaan, Yasmine M AU - Kanaan YM AD - Department of Microbiology, College of Medicine, Howard University, Washington, DC, U.S.A. FAU - Copeland, Robert L Jr AU - Copeland RL Jr AD - Department of Pharmacology, College of Medicine, Howard University, Washington, DC, U.S.A. rlcopeland@howard.edu. LA - eng GR - 2U54 CA091431-06/CA/NCI NIH HHS/United States GR - G12MD007597/MD/NIMHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. PL - Greece TA - Anticancer Res JT - Anticancer research JID - 8102988 RN - 99Z2744345 (Ditiocarb) RN - X8D5EPO80M (Emetine) SB - IM MH - Apoptosis/*drug effects/genetics MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Ditiocarb/*analogs & derivatives/*pharmacology MH - Emetine/*pharmacology MH - Gene Expression Profiling MH - Gene Expression Regulation, Neoplastic/drug effects MH - Humans MH - Male MH - Prostatic Neoplasms/genetics/*pathology OTO - NOTNLM OT - Prostate Cancer OT - apoptosis OT - chemotherapeutic agents OT - dithiocarbamate analogs OT - emetine gene regulation EDAT- 2015/08/09 06:00 MHDA- 2016/04/29 06:00 CRDT- 2015/08/09 06:00 PHST- 2015/08/09 06:00 [entrez] PHST- 2015/08/09 06:00 [pubmed] PHST- 2016/04/29 06:00 [medline] AID - 35/9/4723 [pii] PST - ppublish SO - Anticancer Res. 2015 Sep;35(9):4723-32.