Finding emerging strategies for new use of the “old drug-vitamin C” on cancer treatment-combined with chemotherapy drugs.
This study investigates the mechanisms that pharmacological ascorbate (vitamin C, AA) mediated toxicity in osteosarcoma cells and the effects of pharmacological ascorbate combined with cisplatin (DDP) on osteosarcoma cells in vitro and in vivo.
Pharmacological ascorbate not only promoted the production of hydrogen peroxide (H2O2) to kill osteosarcoma cells, but also improved its lethality to tumor cells by reducing the activity of catalase (CAT). DNA damage was the primary reason leading to osteosarcoma cell death, and depletion of nicotinamide adenine dinucleotide (NAD+) and adenosine triphosphate (ATP), activated apoptosis-inducing factor (AIF) all contribute to ascorbate-induced toxicity. The combination of pharmacological ascorbate with cisplatin showed synergistic effect on osteosarcoma cells in vitro. Pharmacological ascorbate enhanced the efficacy of cisplatin on inhibiting osteosarcoma tumor growth in orthotopic intra-tibial mouse model.
These results suggest that pharmacological ascorbate causes DNA damage and induces osteosarcoma cells death via H2O2 mediated-oxidative stress. The combination of pharmacological ascorbate and cisplatin has synergistic effects on osteosarcoma cells and orthotopic intra-tibial mouse model. Pharmacological ascorbate could be a safe and effective adjuvant agent against osteosarcoma tumor.