Retinoids, Retinoic Acid Receptors, and Cancer

Abstract

Retinoids (i.e., vitamin A, all-trans retinoic acid, and related signaling molecules) induce the differentiation of various types of stem cells. Nuclear retinoic acid receptors mediate most but not all of the effects of retinoids. Retinoid signaling is often compromised early in carcinogenesis, which suggests that a reduction in retinoid signaling may be required for tumor development. Retinoids interact with other signaling pathways, including estrogen signaling in breast cancer. Retinoids are used to treat cancer, in part because of their ability to induce differentiation and arrest proliferation. Delivery of retinoids to patients is challenging because of the rapid metabolism of some retinoids and because epigenetic changes can render cells retinoid resistant. Successful cancer therapy with retinoids is likely to require combination therapy with drugs that regulate the epigenome, such as DNA methyltransferase and histone deacetylase inhibitors, as well as classical chemotherapeutic agents. Thus, retinoid research benefits both cancer prevention and cancer treatment.

Nuclear receptors agonists exert opposing effects on the inflammation dependent survival of breast cancer stem cells

“…[13][14][15] Retinoids are among the most effective pro-differentiating molecules and have been proposed as anticancer agents. 16 Interestingly, it has been shown that all-trans retinoic acid (RA), by inhibiting the activator protein-1, reduces MS formation and the expression of IL6. 17 In inflamed human chondrocytes, retinoids hamper the expression of nitric oxide synthase, cyclooxygenase-2 and of various chemokines, 18 thus leading to argue in favor of their anti-inflammatory activity.…”

Molecular Cloning and Characterization of Bovine CYP26A1 Promoter

“…The molecular mechanism for the repression of endogenous CYP26A1 expression by 3 days ATRA treatment could not be explained clearly in this point. Retinoid treatment might suppress cancers of many tissues including lung tumor and ATRA, as the most active form of RA, is currently used as a chemotherapy drug [19,28]. It is also known that ATRA is involved in the process of programmed cell death (also known as apoptosis) in certain types of tumor cells [21,33].…”

Cancer stem cell hypothesis: a brief summary and two proposals

“…In this context, the so-call differentiation therapy is now widely studied. Retinoic acid (RA, Vitamin A), for example, is one of the most thoroughly studied drugs that are capable of inducing CSC differentiation (Sell 2004;Tang and Gudas 2011;Gudas and Wagner 2011). However, mainly due to retinoid resistance and some serious side effects, the clinical outcome of RA treatment is not satisfactory for many solid tumors (Sell 2004).…”