Objective: 

Prostate cancer is the most common type of cancer in males. Thiosemicarbazone (TSC) and Schiff base and their metal complexes have antitumor activity and are being used as antitumor drugs. It has been revealed with quantitative-structure-activity relationship studies that production of new substances by structural changes in these compounds has different effects. In this study, a new TSC (chemical structure: [(4-(1-phenyl-1-methyl siclobutyl-3-yl)-2-(hydroxybenzyliden hydrazino)tiazol]) and its Cu complex synthesized in our laboratory was investigated in terms of their mechanism of action and antitumor properties by using androgen-dependent (LNCaP) and independent (DU145) human prostate cancer cell lines.

Methods: 

At the first stage of the study, these cell lines were treated with varying concentrations of TSC and Schiff base and their metal complexes (1, 5 and 50mM) for 24h. Antitumor activities of these substances were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Mode of action of these antitumor substances was determined by comet assay (reveals DNA damage).

Results: 

All tested concentrations of TSC, dose-dependently reduced cell viability of LNCaP (p<0.005) while only 50mM concentration of TSC caused a significant decrease in viability of DU145 cells (p<0.05). The high dose of Cu complex of TSC reduced cell viability both in LNCaP and DU145 cell lines (p<0.001). TSC and its Cu complex at 50mM concentration increased DNA breakage in LNCaP cells, but not in DU145 cells.

Conclusions: 

Our results indicate that the tested agents have antitumor activity on human prostate cell lines, and these cytotoxic effects appear to be due to androgen receptor dependent DNA damage.

Acknowledgement: This study was supported by Inonu University BAP (Project # 2010/49).