[#2014-05] Maitake Freilich, Drew et al. Possible Chemosensitizing and Potent Anticancer Effects of D-Fraction in Combination with Vitamin C on Three Prevalent Urologic Cancer Cells

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 G1 cell
cycle arrest, which was also confirmed by the down-regulation of specific cell cycle regulators
(CDK2, CDK4, and cyclin D1) 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