Enhancement of Rotenone Cytotoxicity in the Presence of Bach1 Inhibitors

A novel trend in anticancer therapy is based on the combination of cytotoxic and metabolic drugs. Bach1 is a transcription factor activating glycolysis and increasing proliferation and metastatic potential in cancer cells. The cytotoxic effect was evaluated for a combination of rotenone, an inhibitor of mitochondrial respiration, and two different inhibitors of Bach1 transcription factor in the prostate cancer cell lines (PC3 and Du145) and colorectal cancer (HT-29 and HCT-116) in a kinetic mode. An enhancement of the cytotoxic action of the combination therapy was observed only for the prostate cancer cell lines PC3 and Du145. No enhancement of cytotoxicity of zinc porphyrin in the presence of rotenone was observed for the НСТ-116 line. The HT-29 line was not sensitive to either inhibitor or their combination with rotenone at 24 h incubation. According to the PCR results, HT-29 was the only line showing an extremely high activation of heme oxygenase 1 (HMOX1) in the presence of the Bach1 inhibitor, pointing to the highest level of the antioxidant defense in this cell line. The sensitivity of the prostate cancer cell lines to the combination therapy points to the significant differences in the metabolism between the prostate and colorectal cell lines.