Patterns Cancer Prevention Through Induction of Phase 2 Enzymes
Final rept. 1 Oct 1998-31 Mar 2003
STANFORD UNIV CA
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Virtually all human prostate cancers lose expression of glutathione S-transferase-II, an enzyme that protects against oxidative electrophiles that attack the DNA and result in cancer. Based on this observation, we proposed identifying compounds effective at inducing other carcinogen defense phase 2 enzymes. During our Phase I Award, we identified sulforaphane as the most potent inducer of carcinogen defenses in the prostate cell. We have characterized global effects of sulforaphane in prostate cancer cell lines using cDNA microarray technology that allows large-scale determination of changes in gene expression. These findings argue strongly for a preventive intervention trial involving with sulforaphane. During our Phase 2 Award, we used DNA microarrays to gain insights into the mechanisms of action of methylselenic acid and resveratrol, two additional prostate cancer preventive agents. Our work demonstrates the utility of cDNA microarray technology in understanding the mechanisms of action of preventive agents. We plan to exploit this opportunity in future investigations.
- Medicine and Medical Research