Effect of the mycotoxin deoxynivalenol in combinational therapy with TRAIL on prostate cancer cells

Abstract

Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) is reported as a promising anti-cancer therapeutic target. Unfortunately, prostate cancer cells (PCa) are partially resistant to TRAIL-induced apoptosis limiting its therapeutic potential. The existing body of knowledge suggests that naturally produced compounds, such as mycotoxin deoxynivalenol (DON), might potentially sensitize cells to TRAIL treatment and improve the efficiency of therapy. Previously, we observed that DON induces oxidative stress and apoptosis in PCa cell lines. Thus we addressed here whether DON can sensitize PCa cells to TRAIL-induced apoptosis. Our data demonstrates that three out of four tested PCa cell lines pretreated with DON increased TRAIL-induced apoptosis detected with flow cytometry. This effect was associated with oxidative stress (LNCaP and DU-145 cell line) and elevated DNA damage (DU-145, LNCaP, and 22Rv1 cell lines). Next, in the animal model we inoculated PC tumor to SCKID mice followed by administration of DON intraperitoneally and/or TRIAL intravenously. During 21 days monitoring of tumor growth, the animals received 7 doses of DON, TRAIL, DON+TRAIL or control injections. No significant reduction in tumor mass was observed after combinational treatment of TRAIL and DON compared to 1 μg/kg of body weight DON treatment alone, which itself decreased the tumor growth. However, despite the lack of the TRAIL + DON effect, DON itself inducing apoptosis is an interesting compound worth investigating in the context of other combination therapies.

Keywords: Apoptosis; Cancer; Deoxynivalenol; Mycotoxin; Oxidative Stress; Prostate Cancer; TRAIL.