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Breaking Research For 9-28-99 |
Vitamin C and E
Prevent Androgen Induced Increase in DNA-binding Activity Involved In
Prostate Cancer
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- Effect of antioxidants on
androgen-induced AP-1 and NF-kappaB DNA-binding activity in prostate
carcinoma cells.
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- Ripple MO; Henry WF; Schwarze SR;
Wilding G; Weindruch R
- Institute on Aging, University of
Wisconsin, Madison 53792, USA.
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- J Natl Cancer Inst, 91(14):1227-32
1999 Jul 21
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- Abstract:
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- BACKGROUND:
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- Previous studies have suggested that
male hormones (androgens) and certain forms of oxygen (reactive oxygen
species) are linked to the development of prostate cancer. We
hypothesized that androgens contribute to prostate carcinogenesis by
increasing oxidative stress. We further hypothesized that antioxidants
reduce prostate cancer risk by modulating androgen effects on cellular
processes.
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- METHODS:
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- To test these hypotheses, we looked for:
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- A change in the level of reactive
oxygen species in the presence of androgens.
- Androgen-induced binding activity of
transcriptional activators AP-1 and NF-kappaB, whose activities
are known to be altered during cell proliferation.
- The effect of antioxidants on
androgen-induced transcription factor binding.
RESULTS:
Physiologic concentrations (1 nM) of
5alpha-dihydrotestosterone or 1-10 nM R1881, a synthetic androgen,
produced sustained elevation of AP-1 and NF-kappaB DNA-binding
activity in LNCaP cells, an androgen-responsive human prostate
carcinoma cell line. Androgen-independent DU145 cells (another human
prostate carcinoma cell line) were unaffected by R1881 treatment.
AP-1-binding activity increased 5 hours after 1 nM R1881 treatment;
NF-kappaB DNA-binding activity increased after 36 hours. Both
activities remained elevated for at least 120 hours. Nuclear AP-1 and
NF-kappaB protein levels were not elevated. Antioxidant vitamins C
plus E blocked both androgen-induced DNA-binding activity and
production of reactive oxygen species.
CONCLUSION:
Physiologic concentrations of androgens
induce production of reactive oxygen species and cause prolonged AP-1
and NF-kappaB DNA-binding activities, which are diminished by
vitamins C and E.
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