Retinoids: present role and future potential

Abstract

Summary Vitamin A and its biologically active derivatives, retinal and retinoic acid (RA), together with a large repertoire of synthetic analogues are collectively referred to as retinoids. Naturally occurring retinoids regulate the growth and differentiation of a wide variety of cell types and play a crucial role in the physiology of vision and as morphogenic agents during embryonic development. Retinoids and their analogues have been evaluated as chemoprevention agents, and also in the management of acute promyelocytic leukaemia. Retinoids exert most of their effects by binding to specific receptors and modulating gene expression. 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. In this article we review the use of retinoids in chemoprevention strategies, discuss the cellular consequences of activated retinoid receptors, and speculate on how our increasing understanding of retinoid-induced signalling pathways may contribute to future therapeutic strategies in the management of malignant disease.

The class II tumour suppressor gene H-REV107-1 is a target of interferon-regulatory factor-1 and is involved in IFNγ-induced cell death in human ovarian carcinoma cells

“…While H-REV107-1 contributes to IFNg-dependent growth arrest, TIG3/H-REV107-2 acts in a similar way after induction by retinoic acid. Like IFNg, retinoic acid plays an important role in the regulation of di erentiation and cell growth control, respectively (Evans and Kaye, 1999;Rohwedel et al, 1999). These properties have lead to the application of retinoic acid and IFNg in the therapy of certain leukemias and ovarian cancer (Chelbi-Alix and Pelicano, 1999;Windbichler et al, 2000).…”

OVCA2 is downregulated and degraded during retinoid‐induced apoptosis

“…1,2 The diverse effects of retinoids are mediated by binding to at least 6 retinoid receptors, which fall into 2 subfamilies: retinoic acid receptors (RARs) ␣, ␤ and ␥ and the retinoid X receptors (RXRs) ␣, ␤ and ␥. 3 The RARs and RXRs act as transcription factors, binding as homo-and heterodimers to retinoid response elements in the promoter regions of target genes and thus enhancing or repressing transcription.…”

Retinoic acid induces sodium/iodide symporter gene expression and radioiodide uptake in the MCF-7 breast cancer cell line

“…In clinical studies, tRA and its analogues have proved useful for treatment of a number of cancers (reviewed in ref. 24).…”

“…RARs and RXRs both are expressed in MCF-7 cells, an estrogen receptor (ER)-positive human breast cancer cell line (23). All-trans RA (tRA) inhibits cell cycle progression and induces apoptosis in many tumor cell lines (24), including MCF-7 (25)(26)(27)(28). In clinical studies, tRA and its analogues have proved useful for treatment of a number of cancers (reviewed in ref.…”