Vitamin C supplementation had no side effect in non-cancer, but had anticancer properties in ovarian cancer cells.

Abstract

Vitamin C (Vit C) has been widely used in the treatment and prevention of cancer. Nevertheless, the clinical results are still inconclusive. Using non-cancer (HOSEpiC) and cancer OVCAR-3 cells cultured in basal medium or in ovarian cancer-associated fibroblast (CAF)-supplemented medium, we estimated the dose-dependent effect of Vit C on sodium-ascorbate co-transporters (SVCT1, SVCT2) and glucose transporter (GLUT1) protein expression. Additionally, the action of Vit C on cell proliferation (alamarBlue), membrane permeability (LDH assay), caspase3 activity, the selected cell cycle and apoptosis pathway, poly(ADP-ribose) polymerase-1 (PARP) protein expression, and reactive oxygen species (ROS) activity was determined. We showed different effects of Vit C on the expression of the co-transporter in non-cancer and cancer cells. In non-cancer cells, Vit C, at a pharmacological concentration, increased SVCT2 and decreased GLUT1, while the opposite effect was noted in cancer cells. In cancer cells, Vit C, in a pharmacological dose, decreased cell proliferation through an inhibitory effect on cyclin-dependent kinase 2 (CDK2) (4.4-fold; p<0.01), mainly due to the stimulatory effect on the expression of cyclin-dependent kinase (CDK) inhibitors, such as p21 and p53 (3.2- and 2.8-fold, respectively; p<0.001), but not caspase pathway. The tumour microenvironment caused inefficiency of the lower doses of Vit C in ovarian cancer cells. At a pharmacological dose of 1mM, Vit C decreased PARP expression (1.5-fold; p<0.05). We suggest that it's nontoxic effects on non-cancer cells may be an indicator of its prophylactic use, while in a pharmacological dose Vit C should be considered a possible adjunctive drug in ovarian cancer. However, it is necessary to consider the effect of the CAF.