| 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 inhibit protein biosynthesis on ribosomes in eukaryotes. It has been reported to have a significant role in apoptosis mediated cell death in several cell lines, therefore having a potential for anti-tumorigenic effects for cancer treatments. However, concerns regarding its use emerged due to the fact that it is a protoplasmic poison which impacts muscle, brain, heart tissues; as well as, vascular, gastro-intestinal, and skeletal systems. The goal of this research is to characterize an emetine dithiocarbamate (EMTDTC) analog with potent anti-tumorigenic activity with minimal toxicity to normal prostate tissues, and define the cancer pathways targeted by it. The main techniques used to identify the analog(s) were cytotoxicity assays and MTT to define IC50 values for compound effectiveness; flow cytometry for analyzing apoptotic potential; and real-time PCR arrays to identify changes in gene expression profiles of various signal transduction pathways. Our data suggests that Compounds EMTDTC-H and EMTDTC-I have significant apoptotic potential on prostate cancer cell lines, with minimal effect on normal prostate derived PNT1A cells and their pathways. Both compounds affect multiple carcinogenic pathways, minimizing the possibility for these prostate cancer cell lines to develop compound resistance. We conclude that both compounds EMTDTC-H and EMTDTC-I offer potential to be a therapeutic anti-tumorigenic drug against many different types of prostate cancer, which suggests the independent ability of each compound as a chemotherapeutic agent, or in combinatorial therapy for prostate cancer. |
