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 (ascorbic acid) against cancer development and in treatment of established cancer. The present study investigated whether ascorbic acid demonstrates a therapeutic benefit for prostate cancer.


METHODS
Androgen-independent (DU145) and androgen-dependent (LNCaP) human prostate cancer cell lines were both treated in vitro with vitamin C (0-10 mM). Cell counts, cell viability, and thymidine incorporation into DNA were determined.


RESULTS
Treatment of DU145 and LNCaP cells with vitamin C resulted in a dose- and time-dependent decrease in cell viability and thymidine incorporation into DNA. Vitamin C induced these changes through the production of hydrogen peroxide; addition of catalase (100-300 units/ml), an enzyme that degrades hydrogen peroxide, inhibited the effects of ascorbic acid. Superoxide dismutase, an enzyme that dismutates superoxide and generates hydrogen peroxide, did not prevent decreases in 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-alpha-tocopherol did not counteract the effects of ascorbic acid on thymidine incorporation suggests that vitamin C-induced changes do not occur through the generation of these ROS.


CONCLUSIONS
Vitamin C inhibits cell division and growth through production of hydrogen peroxide, which damages the cells probably through an as yet unidentified free radical(s) generation/mechanism. Our results also suggest that ascorbic acid is a potent anticancer agent for prostate cancer cells.
Maramag
C
C
Division of Urologic and Transplantation Surgery, University of Massachusetts Medical Center, Worcester 01655, USA.
Menon
M
M
Balaji
K C
KC
Reddy
P G
PG
Laxmanan
S
S
D000728:Androgens / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D001386:Azides / Q000494:pharmacology; D002452:Cell Count / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006873:Hydroquinones / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D019810:Sodium Azide; D013482:Superoxide Dismutase / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured
D000728:Androgens; D000970:Antineoplastic Agents; D001386:Azides; D004273:DNA, Neoplasm; D005609:Free Radicals; D006873:Hydroquinones; D014316:Tritium; D017665:Hydroxyl Radical; D019810:Sodium Azide; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D001205:Ascorbic Acid; D013936:Thymidine; C031927:hydroquinone