EFFECT OF VITAMIN-C ON PROSTATE-CANCER CELLS IN-VITRO - EFFECT ON CELL NUMBER, VIABILITY, AND DNA-SYNTHESIS

BACKGROUND. Many studies describe the protective role of vitamin C (as corbic acid) against cancer development and in treatment of establishe d cancer. The present study investigated whether ascorbic acid demonst rates a therapeutic benefit for prostate cancer. METHODS. Androgen-ind ependent (DU145) and androgen-dependent (LNCaP) human prostate cancer cell lines were both treated in vitro with vitamin C (0-10 mM). Cell c ounts, cell viability, and thymidine incorporation into DNA were deter mined. RESULTS. Treatment of DU145 and LNCaP cells with vitamin C resu lted in a dose- and time-dependent decrease in cell viability and thym idine incorporation into DNA. Vitamin C induced these changes through the production of hydrogen peroxide; addition of catalase (100-300 uni ts/ml), an enzyme that degrades hydrogen peroxide, inhibited the effec ts of ascorbic acid. Superoxide dismutase, an enzyme that dismutates s uperoxide and generates hydrogen peroxide, did not prevent decreases i n cell number and DNA synthesis, suggesting further the involvement of hydrogen peroxide in vitamin C-induced changes. These results clearly indicate that reactive oxygen species (ROS) are involved in vitamin C -induced cell damage. However, that singlet oxygen scavengers such as sodium azide and hydroquinone and hydroxyl radical scavengers such as D-mannitol and DL-cr-tocopherol did not counteract the effects of asco rbic acid on thymidine incorporation suggests that vitamin C-induced c hanges do not occur through the generation of these ROS. CONCLUSIONS. Vitamin C inhibits cell division and growth through the production of hydrogen peroxide, which damages the cells probably through an as yet unidentified free radical(s) generation/mechanism. Our results also su ggest that ascorbic acid is a potent anticancer agent for prostate can cer cells. (C) 1997 Wiley-Liss, Inc.