Between Death and Survival: Retinoic Acid in Regulation of Apoptosis

The vitamin A metabolite all-trans-retinoic acid (RA) regulates multiple biological processes by virtue of its ability to regulate gene expression. It thus plays critical roles in embryonic development and is involved in regulating growth, remodeling, and metabolic responses in adult tissues. RA can also suppress carcinoma cell growth and is currently used in treatment of some cancers. Growth inhibition by RA may be exerted by induction of differentiation, cell cycle arrest, or apoptosis, or by a combination of these activities. Paradoxically, in the context of some cells, RA not only fails to inhibit growth but, instead, enhances proliferation and survival. This review focuses on the involvement of RA in regulating apoptotic responses. It includes brief overviews of transcriptional signaling by RA and of apoptotic pathways, and then addresses available information on the mechanisms by which RA induces apoptosis or, conversely, inhibits cell death and enhances survival.