Dynamic effects of Retinoic Acid isomers on cancer and physiology

Retinoids, natural and synthetic vitamin A derivatives, are used as cancer chemo-preventive compounds. However, clinical trials have shown that retinoids can be deleterious leading to an increased incidence of neoplasias. The conflicting data regarding the pro/anti-oxidant potential of different retinoids molecules, stimulated us to investigate the effect of all-trans-Retinoic Acid (RA) on tumor cell proliferation in vitro. Dose-response treatment with RA at physiological doses promotes cell proliferation or autophagy while pharmacological doses results in apoptosis. RA is also implicated in a post-translation modification that modify the activity of the mitochondrial oxo-chetoglutarate carrier. Retinoids are often used as part of a combined therapy. We have elucidated the molecular mechanism by which treatment with rosiglitazone (BRL) and 9-cis-retinoic acid (9cRA) triggers apoptotic events in breast cancer cells as novel therapeutic tool for patients who develop resistance to anti-estrogen therapy. Recently 9cRA was found as endogenous in pancreas highlighted its rule in glucose stimulated insulin secretion mechanism and glucose homeostasis, establishing it as autocoid hormone.