The aspirin metabolite, salicylate, inhibits 7,12-dimethylbenz[a]anthracene-DNA adduct formation in breast cancer cells.
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.
Abbadessa
Giuliana
G
Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Torino, Italy.
Spaccamiglio
Angela
A
Sartori
Maria Luisa
ML
Nebbia
Carlo
C
Dacasto
Mauro
M
Di Carlo
Francesco
F
Racca
Silvia
S
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000633:toxicity; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D051545:Cyclooxygenase 1 / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D018736:DNA Adducts / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012459:Salicylates / Q000494:pharmacology*
C059444:7,12-dimethylbenz(a)anthracene-DNA adduct; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D018736:DNA Adducts; D012459:Salicylates; D015127:9,10-Dimethyl-1,2-benzanthracene; D019363:Cytochrome P-450 CYP1A1; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2