Dichloroacetate and PX-478 exhibit strong synergistic effects in a various number of cancer cell lines

Abstract Background One key approach for anticancer therapy is drug combination. Drug combinations can help reduce doses and thereby decrease side effects. Furthermore, the likelihood of resistance reduced. Distinct alterations in tumor metabolism have been described past decades, but has yet to be targeted clinical cancer therapy. Recently, we found evidence synergism between dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor, HIF-1? inhibitor PX-478. In this study, aimed analyse cell lines different types identify underlying biochemical mechanisms. Methods The dose-dependent antiproliferative effects single drugs their combination were assessed using SRB assays. FACS, Western blot HPLC analyses performed investigate changes reactive oxygen species levels, apoptosis cycle. Additionally, real-time metabolic (Seahorse) with DCA-treated MCF-7 cells. Results DCA PX-478 produced synergistic all eight tested, including colorectal, lung, breast, cervical, liver brain cancer. Reactive generation played important roles synergism. proliferation was inhibited by treatment. Conclusions Here, that these metabolism-targeting compounds exhibited potent across tested lines. Thus, highly recommend two progression vivo translational trials.