Possible Chemosensitizing and Potent Anticancer Effects of D-Fraction in Combination with Vitamin C on Three Prevalent Urologic Cancer Cells

Abstract

Chemotherapy is currently one of the most common therapeutic options for cancer patients despite the poor efficacy with considerable side effects. We then examined if D-fraction (DF), a bioactive mushroom extract, could potentiate (poor) anticancer effects of those drugs in vitro . Three urologic cancers, prostate, bladder, and kidney cancers, were tested with various chemotherapeutic drugs and their combinations with DF. Compared to individual drugs alone, combinations of drugs and DF have improved anticancer activity, resulting in the significant (P < 0.05) cell viability reduction in all three cancer cells. As vitamin C (VC) has been postulated to potentiate the bioactivity of DF, this possibility was also examined. The specific combination of DF (300 μg/ml) and VC (200 μM) indeed led to the drastic (≥90%) viability reductions in all three cancer cells. To have a better understanding of such a profound viability reduction, the effect of DF/VC combination on cell cycle was examined next. Cell cycle analysis indicated that this combination induced a G 1 cell cycle arrest, which was also confirmed by the down-regulation of specific cell cycle regulators (CDK2, CDK4, and cyclin D 1 ) detected on western blots. Moreover, it was crucial to address if the DF/VC-induced viability reduction could be also linked to apoptosis. Western blot analysis revealed that anti-apoptotic bcl-2 was down-regulated while pro-apoptotic Bax was up-regulated with DF/VC combination in all cancer cells, indicating induction of apoptosis. Therefore, the DF/VC combination could ultimately induce apoptosis, accounting for the severe cell viability reduction. In conclusion, DF appears to be a promising agent with chemosensitizing effect, enhancing the efficacy of chemotherapeutic drugs, and its combination with VC exhibits a potent anticancer effect, which is far superior to any combinations of drugs and DF tested in three prevalent urologic cancer cells.