Synergistic anticancer action of retinoic acid and unsaturated fatty acids on human breast tumor cell lines in vitro

QUIROGA PL; SORIA, ELIO A; VALENTICH MA; EYNARD, ALDO R

CURRENT PHARMACEUTICAL DESIGN.

BENTHAM SCIENCE PUBL LTD

Lugar: Oak Park; Año: 2012

1381-6128

Epidemiological and experimental studies indicated that both retinoic acid (RA) and unsaturated fatty acids (UFAs) have antineoplastic properties. But, paradoxically, data about the relevance of the summing action of these nutritional factors are scarce. We evaluated possible synergistic anti-cancer effects of RA and UFAs on breast cancer cells in vitro. Materials: Mammary cancer cells MCF-7 and ZR-75-1 were cultured with RA alone or combined with different types of UFAs: ω-6 (GLA; 18:3, gamma-linoleic acid) and ω-3 (EPA; 20:5, eicosapentaenoic acid) and a non-essential one, ω-9 (OA; 18:1, oleic acid) and its derivate 20 carbons (ETA; 20:3, eicosatrienoic acid). Results: The FA profile of cells membranes correlated with their exogenous administration. Of all the fatty acids tested, GLA was less conclusive, while OA and ETA exhibited better pro-oxidant and cytotoxic effects, whereas EPA induced desirable cytodifferentiation. ω-3 and ω-9 families (EPA and OA/ETA, respectively) induced marked cellular stress in both cell lines, but was more evident in ZR-75-1 cells. Also, UFAs increased cell susceptibility to stress, enhancing the observed RA antitumor capacity. Conclusions: Our results suggest that simultaneous use of retinoic acid and certain unsaturated fatty acids, mainly from ω-3 and ω-9 families, potentiate antineoplastic potential of each other and its clinical potential needs to be studied in future.