title: Involvement of PPARalpha in the growth inhibitory effect of arachidonic acid on breast cancer cells.
abstract: Epidemiological studies suggest that dietary PUFA may influence breast cancer progression. n-3 PUFA are generally known to exert antitumour effects, whereas reports relative to n-6 PUFA anti-carcinogen effects are controversial. Arachidonic acid (AA; 20:4n-6) and its metabolites have been shown to inhibit the growth of human breast cancer cell lines, even if the downstream mechanisms by which AA may influence carcinogenesis remain unresolved. We explored the molecular basis for AA influence on proliferation, signal transduction and apoptosis in two human breast cancer cell lines, MCF-7 and MDA-MB-231. In both cell lines AA inhibited cell growth in a dose-dependent manner, even if MDA-MB-231 was somewhat more growth-inhibited than MCF-7. AA decreased extracellular signal-regulated protein kinase 1/2 phosphorylation level, and positively modulated PPARgamma and PPARalpha expression, with only a slight effect against PPARbeta/delta. In addition, AA increased Bak (an apoptosis-regulating protein) expression and reduced procaspase-3 and -9 levels only in MDA-MB-231 cells, thus indicating that the growth inhibitory effect can be correlated with apoptosis induction. In both cell lines the use of a specific antagonist made it possible to establish a relationship between AA growth inhibitory effect and PPARalpha involvement. AA decreases cell proliferation most likely by inducing apoptosis in MDA-MB-231 cells, while in the MCF-7 cell line the growth inhibitory activity can be attributed to the inhibition of the signal transduction pathway involved in cell proliferation. In both cases, the results here presented suggest PPARalpha as a possible contributor to the growth inhibitory effect of AA.
authors.affiliation: Department of Experimental Medicine and Oncology, University of Torino, C. Raffaello 30, 10125 Torino, Italy. claudia.bocca@unito.it
authors.forename: Claudia
authors.initials: C
authors.lastname: Bocca
authors.forename: Francesca
authors.initials: F
authors.lastname: Bozzo
authors.forename: Germana
authors.initials: G
authors.lastname: Martinasso
authors.forename: Rosa Angela
authors.initials: RA
authors.lastname: Canuto
authors.forename: Antonella
authors.initials: A
authors.lastname: Miglietta
mesh_terms: D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects; D016718:Arachidonic Acid / Q000494:pharmacology*; D015153:Blotting, Western / Q000379:methods; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: D047493:PPAR alpha; D012333:RNA, Messenger; D016718:Arachidonic Acid; D048049:Extracellular Signal-Regulated MAP Kinases