There is evidence that
aspirin and other non-steroidal anti-inflammatory drugs may be
protective agents against
cancer in the gastrointestinal tract. These effects are particularly well documented for the colon and rectum. Some epidemiological and experimental studies have suggested that
aspirin could also be a chemopreventive agent against
breast cancer. We investigated the effects of the
aspirin metabolite,
salicylate (SA), on 7,12-dimethylbenz[a]
anthracene (
DMBA)-DNA adduct formation as well as on the expression of the
enzymes involved in the
carcinogen bioactivation pathway, in particular
cytochrome P450 1A (CYP1A) and
cyclooxygenases (COX-1 and COX-2). The effects of the test
drug were examined in both the
human mammary carcinoma cell line, MCF-7, and mammary cells derived from DMBA-induced rat mammary tumours (RMTCs). In this study, we also reported the effects of SA on cell growth and viability in
breast cancer cells (BCCs). The results demonstrated that
DMBA-DNA adduct formation in both
cancer cell lines was inhibited by SA at concentrations of > or = 2.5 mM. CYP1A was undetectable in RMTCs while CYP1A induction by
beta-naphthoflavone in MCF-7 cells was significantly inhibited by SA in a concentration-dependent manner.
Aspirin did not affect COX-1 expression in either of the BCCs. COX-2 was not detected in MCF-7 cells, but its expression in RMTCs was inhibited by SA treatment, which also significantly reduced BCC growth, but failed to cause cell death by
necrosis or apoptosis. These data suggest that inhibition of
DMBA-DNA adduct formation may contribute to
aspirin breast cancer chemopreventive action and indicate that this
drug can act in the first stage of
carcinogenesis.