Retinoids, Apoptosis and Cancer

Retinoids are a class of natural and synthetic vitamin A analogs structurally related to all-trans-retinoic acid (ATRA). Natural retinoids are involved in the physiology of vision and as morphogenic agents during embryonic development they are also known to play a major role in regulating growth and differentiation of a wide variety of normal and malignant cell types, and, indeed, they can in various ways inhibit cell proliferation, induce differentiation and cell death by apoptosis. The development of new active retinoids and the identification of two distinct families of retinoid receptors has led to an increased understanding of the cellular effects of activation of these receptors and of mechanisms involved in the retinoid-induced apoptosis. In this review a brief summary of cellular pathways relevant to programmed cell death is given together with therapeutic potentialities of retinoids having apoptotic activity. Structure-activity relationship studies concerning the importance of different stereochemistry at the C9 double bond of retinoids in conferring apoptotic activity will be described. It will be also described the preparation and the potent cytotoxic and apoptotic activity of a novel class of heterocycle-bridged arotinoids.