Effects of vitamin C on androgen receptor mediated actions in human prostate adenocarcinoma cell line LAPC-4.
OBJECTIVE
To examine the effects of vitamin C (VC) on androgen receptor (AR)-mediated functions in a human prostate cancer cell line, Los Angeles prostate cancer (LAPC-4). VC is an essential dietary substance in the maintenance and preservation of vital functions in humans. However, the role of VC in prostate cancer remains to be elucidated.


METHODS
Cell proliferation and the expression of two well-known androgen regulated proteins, prostate-specific antigen and human glandular kallikrein-2, were studied in the presence of VC.


RESULTS
In the presence of androgen and VC, both cell growth and the expression of prostate-specific antigen and human glandular kallikrein-2 proteins were decreased. Moreover, AR-mediated transcription activity of the prostate-specific antigen gene was suppressed with VC, similar to the phenomenon observed when cells were treated with hydrogen peroxide. These effects were reversed with catalase. However, additional studies did not reveal changes in the expression level of AR protein or its androgen-binding activity with the addition of VC.


CONCLUSIONS
The results of our study suggest that the pro-oxidant property of VC might be one of the mechanisms by which it modulates AR-mediated function in LAPC-4 cells.
Wang
Ming-Hsien
MH
Department of Urology and Biochemistry/Molecular Biology, Mayo Graduate School, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Abreu-Delgado
Yamilka
Y
Young
Charles Y F
CY
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000728:Androgens; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D017930:Genes, Reporter; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000096:biosynthesis / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000187:drug effects* / Q000502:physiology; D020840:Tissue Kallikreins / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000728:Androgens; D016588:Anticarcinogenic Agents; D009363:Neoplasm Proteins; D011944:Receptors, Androgen; D020840:Tissue Kallikreins; D017430:Prostate-Specific Antigen; D001205:Ascorbic Acid