Combination therapy with vitamins C plus E inhibits survivin and human prostate cancer cell growth.
BACKGROUND
We postulated that combinations of C and E vitamins modulate the antioxidant network and blocks survivin gene expression in androgen-responsive and non-responsive human prostate cancer cell (HPCC) lines.


METHODS
ALVA-101 and DU-145 cell growth and apoptosis were estimated using the Cell Titer 96 AQ and cell death detection ELISA. Reverse transcription-polymerase chain reaction, Western blot and electrophoretic mobility shift assay were used to quantify survivin mRNA, protein, nuclear factor kappa B (NF-kappaB), and activator protein-1 (AP-1).


RESULTS
All the tested combinations of vitamins C and E (25-100 microM, 72 hr) reduced cell growth (4-83%). Vitamin C enhanced the growth suppressive effect of vitamin E. Apoptosis was enhanced (25-45%) (vitamins = 100 microM, 24 hr). Survivin mRNA was decreased (26-29%) (vitamins = 250 microM, 24 hr), and survivin protein was decreased (>90%) (vitamins = 100 microM, 72 hr). NF-kappaB and AP-1 activities were increased (vitamins = 100 microM, 24 hr).


CONCLUSIONS
The combinations of vitamins C and E are potent inducers of apoptosis in HPCC and suppressers of surviving, an antiapoptotic factor.
Gunawardena
Kushlani
K
Departments of Internal Medicine and Pathology, ARUP Institute, University of Utah, Salt Lake City, Utah 84108, USA.
Campbell
L David
LD
Meikle
A Wayne
AW
D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects*; D015853:Cysteine Proteinase Inhibitors / Q000096:biosynthesis* / Q000235:genetics; D004359:Drug Therapy, Combination; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology*
D000975:Antioxidants; C107489:BIRC5 protein, human; D015853:Cysteine Proteinase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D014810:Vitamin E; D001205:Ascorbic Acid