CONICET | Buscador de Institutos y Recursos Humanos

Breast cancer (BC) is the most frequent cancer occurring in women [1]. Epidemiological data have linkedn-3 polyunsaturated fatty acid (PUFA) consumption to lower incidence of BC and several experimental studies showed theanti-proliferative effects of n-3 PUFAs in different BC models [2]. Chia oil is rich in α-linolenic acid (ALA 18:3 n-3),while corn oil is rich in linoleic acid (LA 18:2 n-6). Angiogenesis is a tightly regulated process involving endothelial cell(EC) proliferation, migration and tube formation [3]. Docosahexaenoic acid (DHA, 22:6 n-3) a downstream metabolitefrom ALA, has been demonstrated to regulate cancer-related angiogenesis, while arachidonic acid (AA, 20:4 n-6) promotesangiogenesis [4]. In addition, aspirin (ASA) has antineoplastic effects that are mediated at least in part by metabolitesderived from acetylated COX-2 [5]. The study was aimed to determine a possible role of dietary n-3 PUFAs on BC growthand, in particular, the effect of DHA metabolites from ASA-acetylated COX-2 in cancer-related angiogenesis.Methods: 40 BALB/c mice were fed 1) a Chia Oil (ChO)-rich (n-3), or 2) a Corn Oil (CO)-rich diet (n-6). Afterwards,mice were inoculated with mouse BC cells (LM3) and tumour growth parameters were recorded after 35 days. Mitotic orapoptotic figures were assessed in haematoxylin/eosin-stained tumour sections. Human endothelial cells (ECs) were usedat 2nd to 6th passage and treated with DHA or AA (1-50μM) for 24h in the presence or absence of ASA (50 μM). Selectedexperiments were performed with 17-R HDoHE (100nM-3μM), a DHA metabolite derived from acetylated COX-2. ECviability was analyzed with the MTT assay. The angiogenetic process was evaluated using a) the wound healing assay, b) amicro chemotaxis chamber, and c) matrigel.Results: After 35 days tumour incidence was higher in CO-fed compared with ChO-fed mice (100 vs 85%, p