Cytotoxic effects of combinational therapy of ascorbic acid and 3PO on breast and non‐small cell lung cancer cells

Abstract

Many malignant cancer cells exhibit a high glycolytic rate even in the presence of oxygen. The Warburg effect has lead to the selective targeting of glycolytic enzymes by many novel therapeutic agents. Mitochondrial respiratory injury and damaged oxidative stress mechanisms within the cell are postulated to contribute to this cancerous phenotype. Therapies that inhibit glycolysis and induce oxidative stress may be particularly effective. We used the glycolysis inhibitor 3PO and pro‐oxidant ascorbic acid in combination against MCF7 and H1299 cells to test this hypothesis. We observed a synergistic loss of cell viability when a combination of drugs was used against H1299 cells, which correlated with induction of DNA damage and apoptosis in H1299. Interestingly, MCF7 cells did not respond to the treatment with the same efficacy as H1299 cells, implying a stronger resistance to 3PO and ascorbic acid. Reactive oxygen species (ROS) levels in drug treated H1299 cells display an initial increase and a later diminished degree of ROS. Mitochondrial dysfunction was also assessed to see if apoptosis proceeded via the intrinsic apoptotic pathway in H1299 cells. Data suggests at higher doses of combination drug therapy, mitochondrial integrity is disrupted. Our results suggest that this combinational therapy against glycolysis and oxidative stress show synergistic, cytotoxic results in non‐small cell lung cancer. This research was supported by the Medicus Society and the U.S. Department of Defense USAMRMC/TATRC, Award W81XWH‐09‐2‐0022.