Apoptotic Effects of Novel Dithiocarbamate Analogs of Emetine in Prostate Cancer Cell Lines.

Abstract

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.

• Authors: Zebalda D Bamji, Kareem N Washington, Emmanuel Akinboye, Oladapo Bakare, Yasmine M Kanaan, Robert L Copeland Jr
• Journal: Anticancer research (Anticancer Res) Vol. 35 Issue 9 Pg. 4723-32 (Sep 2015) ISSN: 1791-7530 [Electronic] Greece
• PMID: 26254362 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• Ditiocarb
• Emetine

Topics

• Apoptosis (drug effects, genetics)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Ditiocarb (analogs & derivatives, pharmacology)
• Emetine (pharmacology)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Male
• Prostatic Neoplasms (genetics, pathology)