Retinoids and Reactive Oxygen Species in Cancer Cell Death and Therapeutics

Abstract

Retinoids are a large family of structurally related natural and synthetic molecules that exhibit a variety of effects in embryogenesis and adult life. The parent compound of retinoids is vitamin A which was first discovered for its impact on vision and later on cell proliferation, cell differentiation, and cell death. Clinically, retinoids were used for six decades in cancer management as they exhibit antitumor effects such as inhibiting cellular proliferation, inducing apoptosis, modulating cell cycle, and cell differentiation. Initially, early research focused on the mechanism of action of retinoids by their binding to retinoic acid receptors. However, recently accumulated evidence points that retinoids can act independent of the retinoid receptor signaling pathway for example by inducing stress, changes in redox balance, and reactive oxygen species (ROS) generation, and modulation of pathways that do not require binding of transcription factors to retinoic acid responsive DNA sequences. This review focuses on the mechanism of action of natural as well as synthetic retinoids, in particular, on the generation of ROS in in vitro and in vivo tumor models. A better understanding of the effects of retinoids on cellular redox balance and oxidative stress will impact future strategies of cancer management and therapy.