Valproic Acid; Evidence for Sensitization of Prostate Cancer Cells to Doxorubicin

Prostate cancer is the second most common malignancy in men. Although chemotherapy, asthe main treatment approach in advanced stage prostate cancer, can increase the survivalrate of patients, but these agents possess severe side effects. This problem has fueledattempts to reduce the dose of chemotherapeutic drugs by combination therapy. Valproic acid(VA), a histone deacetylase inhibitor, seems a suitable agent for this purpose. The presentstudy aimed to assess the effects of VA on cytotoxic activity of doxorubicin against PC-3 cellline. PC-3 cells were seeded in 96-well plates. Three days later, when the cells were enteredto the logarithmic phase of growth, exposure period was started by adding 1 nM, 3.3 nM, 10nM, 33 nM and 100 nM concentrations of doxorubicin alone or in combination with 0.1 mMand 1 mM concentrations of VA. 72 hours later, the drugs were removed from the wells. Inorder to demonstrate retention of regenerative capacity of the exposed survived cells, a 96hours recovery period were considered. Finally, MTT (5mg/mL) was added to each plate andafter incubation for 4 hours, absorbance was recorded at 570 nm. VA alone inhibitedsignificantly the proliferation of prostate cancer cells at both 0.1 mM and 1 mM concentrations(P < 0.001). Growth inhibitory effects of doxorubicin were significantly higher when this agentwas combined by VA (P < 0.05). VA can be considered as a promising drug in treatment ofprostate cancer. Also this agent seems to sensitize the neoplastic cells of prostate cancer tothe cytotoxic effects of doxorubicin.