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Prostate Cancer and Prostatic Diseases (2004) 7, 5456& 2004 Nature Publishing Group All rights reserved 1365-7852/04 $25.00www.nature.com/pcanSynergistic effect of vitamin E and
selenium in human prostate
cancer cell linesV Venkateswaran1, NE Fleshner2 & LH Klotz1*1Division of Urology, Sunnybrook and Womens College Health Science Centre, Toronto,
Ontario, Canada; and2Division of Urology, The Princess Margaret Hospital, Ontario,
CanadaVitamin E and selenium are the two most popular dietary supplements used to
prevent prostate cancer. The hypothesis that these antioxidants reduce prostate
risk is being tested in the selenium and vitamin E chemoprevention trial
(SELECT). We hypothesize that selenium potentiates vitamin E-induced inhibition
of prostate cancer cell growth in vitro. Prostate cancer cell populations growing
asynchronously were treated with a combination of vitamin E and selenium and
processed for flow cytometric analysis. Prostate cancer cells treated with a
combination of the antioxidants revealed that selenium potentiates vitamin E-
induced inhibition of LNCaP cells in vitro. This was demonstrated by a reduction
in the percentage of cells in the S phase. This crucial finding confirms our
previous observations that antioxidant molecules act via distinct mechanistic
pathways. These independent biological effects can be exploited in order to
augment the anticancer properties of individual agents. These data also validate
the two factorial design of the SELECT trial, permitting pairwise comparisons
between agents in combination and alone.Prostate Cancer and Prostatic Diseases (2004) 7, 5456. doi:10.1038/sj.pcan.4500707
Published online 27 January 2004Keywords: vitamin E; selenium; prostate cancer; preventionIntroductionClinical and epidemiological evidence suggests that the
progression of prostate cancer from microfoci to clinical
disease is preventable. Recent clinical studies have
indicated that selenium and vitamin E are promising
candidates for prostate cancer prevention. The observations are based on secondary analysis of large chemoprevention trials in other cancers.1,2 To test the
hypothesis that these micronutrients have a preventive
effect on prostate cancer, a large-scale clinical trial of
selenium and vitamin E (SELECT) has been initiated
recently. This is an international phase III, randomized,
double-blind, placebo-controlled trial, designed to test
the efficacy of selenium and vitamin E alone and in
combination. While the clinical interest in the use of
vitamin E and selenium together is widespread, there
have been no laboratory studies of the potential
synergistic effects of vitamin E and selenium.Selenium is a nonmetallic trace element essential...