Apoptotic effects of novel dithiocarbamate analogs of emetine in prostate cancer cell lines

Zebalda D. Bamji, Kareem N. Washington, Emmanuel Akinboye, Oladapo Bakare, Yasmine M. Kanaan, Robert L. Copeland

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)4723-4732
Number of pages10
JournalAnticancer research
Volume35
Issue number9
StatePublished - Sep 1 2015

Keywords

  • Apoptosis
  • Chemotherapeutic agents
  • Dithiocarbamate analogs
  • Emetine gene regulation
  • Prostate Cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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