Antiproliferative and Antimigratory Effects of Isoeugenol-Based Polyphenolic Compounds.

Abstract

In this research, the effect of synthesized polyphenolic compounds 4 and 5 at the cellular and molecular levels was examined. Within this framework, related substances effects on prostate cell (PC3) viability were evaluated by MTT analysis, and their effects on migration were examined by in vitro scratch analysis. Additionally, mRNA expression levels of gene regions known to be associated with metastasis and apoptosis were determined by real-time quantitative PCR. DNA binding researches have also been carried out to determine the DNA compound interactions. As a consequence, it was determined that 4 and 5 obstructed the PC3 cell viability in a manner that is dose- and time-dependent. The IC50 dose of 4 and 5 in PC3 cell was found to be 60.14 μM, 15.51 μM for 48 h, respectively. 4 and 5 substances showed suppressive effect on migration of PC3 cancer cells in the in vitro scratch model created at IC50 concentrations. Compared to the negative control, PC3 cancer cells treated with 4 and 5 showed 24 % and 46 % closure, respectively, at the wound site at 48 h. 4 and 5 compounds were treated at IC50 concentrations with PC3 cancer cells for 48 h, and then the effects of both compounds on the gene expression, that have been linked to metastasis and apoptosis, at the mRNA level were evaluated. It was determined that 4 decreased the expression of the HIF1-α gene 294 times and 5 decreased the expression of the said gene 30 times. In addition, both 4 and 5 were able to significantly increase the Bax/Bcl-2 mRNA expression ratio (32.65 and 10.46 fold, P<0.0001) in PC3 cells as compared to untreated cells after 48 h. Finally, when DNA binding analysis results were evaluated, it was determined that both polyphenolic compounds did not bind to DNA at the tested time and concentrations and did not cause DNA breaks.