Retinoids in Cancer Chemoprevention (original) (raw)
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Journal of Dermatological Treatment, 2017
Retinoids are a class of compounds derived from vitamin A or have structural and/or functional similarity with vitamin A. They are classified into three generations based on their molecular structures. Inside the body, retinoids bind to several classes of proteins including retinoidbinding proteins and retinoid nuclear receptors. This eventually leads to the activation of specific regulatory regions of DNAcalled the retinoic acid response elementsinvolved in regulating cell growth, differentiation and apoptosis. Several clinical trials have studied the role of topical and systemic retinoids in disease, and research is still ongoing. Currently, retinoids are used in several fields of medicine. This paper aims to review the structure, mechanisms of action and adverse effects of retinoids, as well as some of their current uses in Dermatology.
Specific Antagonist of Retinoid Toxicity in Mice
Toxicology and Applied Pharmacology, 1996
Retinoids bind and transactivate a group of receptors, the retinoic acid receptors (RARs) 2 a, b, and g, that belong to AGN 193109 was recently identified as a potent retinoic acid receptor (RAR) antagonist in vitro. The purpose of the present the superfamily of steroid nuclear receptors. Interaction with study was to determine if AGN 193109 functions as an RAR antag-RARs, which are thought to function as heterodimers in onist in vivo and thus could prevent and/or treat retinoid toxicity. combination with retinoid X receptors in vivo, probably ac-Female hairless mice were treated topically for 5 consecutive days counts for the pleiotropic effects of retinoids, including efwith the synthetic retinoic acid receptor agonist (E)-4-[2-(5,6,7,8fects on epithelial cell proliferation and differentiation tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propen-1-yl]benzoic (Mangelsdorf et al., 1994). acid (TTNPB) alone or in the presence of a 1-, 4-, or 16-fold The therapeutic activity of the presently marketed retimolar excess of AGN 193109. TTNPB caused skin flaking, skin noids is accompanied by a broad spectrum of toxicities, abrasions, and splenomegaly, and these effects were blocked in a including skin irritation, mucocutaneous toxicity, hypertridose-dependent fashion by AGN 193109 cotreatment. In the same glyceridemia, and bone toxicity (Kovacs and Shear, 1993; model, AGN 193109 also decreased topical irritation induced by Armstrong et al., 1994). These toxicities, which can be serithe natural RAR agonist, all-trans-retinoic acid. To determine if topical AGN 193109 could block toxicity induced by an oral retious but seldom life-threatening, recapitulate the symptoms noid, mice were treated by gavage with TTNPB (0.75 mmol/kg/ observed after acute or chronic vitamin A intoxication, colday) and topically with 0, 0.3, or 1.2 mmol/kg/day of AGN 193109 lectively known as hypervitaminosis A syndrome (Clark, for 4 days. TTNPB treatment alone caused cutaneous irritation 1971; Silverman et al., 1987). Currently, there is no specific and weight loss, and these effects were inhibited by AGN 193109 treatment for retinoid intoxication, and relief can be obtained cotreatment. To determine if AGN 193109 could be used to treat only by limiting further exposure to retinoids. Given the preexisting retinoid toxicity, mice were pretreated topically on increasing clinical use of retinoids (Vershoore et al., 1993; Days 1-2 with TTNPB (0.72 mmol/kg/day) and then treated topi-Graf et al., 1995) and the likelihood that more potent syncally on Days 3-5 with 0, 1.44, 7.2, or 36.0 mmol/kg of AGN thetic retinoids will become available, the possibility of over-193109. TTNPB pretreatment caused precipitous weight loss and, dose with retinoids (Lindemayr, 1986) is increasingly probain the absence of AGN 193109 intervention, 60% mortality. AGN ble. Thus, the availability of a specific antagonist of retinoid 193109 treatment at all dose levels significantly accelerated recovery of body weight and prevented death in TTNPB-intoxicated intoxication would be desirable. In addition to its potential mice. These data demonstrate that AGN 193109 is a potent RAR clinical use, a retinoid antagonist would be a valuable experiantagonist and a potential antidote of retinoid intoxication in vivo. mental tool for probing the role of RARs in biological pro-In addition to potential clinical applications in the prevention cesses, including retinoid toxicology. and treatment of retinoid toxicity, AGN 193109 should provide a Recently, a number of retinoid antagonists have been synpowerful experimental tool for the elucidation of retinoid biology. thesized (
Retinoids and their biological effects against cancer
International Immunopharmacology, 2014
There are more than 4000 natural and synthetic molecules structurally and/or functionally related to vitamin A. Retinoids are a class of these compounds that are structurally associated to vitamin A. The retinoids have a wide spectrum of functions. Retinoic acid, which is the active metabolite of retinol, regulates a wide range of biological processes including development, differentiation, proliferation and apoptosis. It suppresses carcinogenesis in tumorigenic animal models for the skin, oral, lung, breast, bladder, ovarian and prostate. It is important how major retinoids may act in cancer treatment or prevention. The reports have indicated that lower levels of vitamin A in humans may be associated with relative type 1 cytokine dominance and a higher proportion of NK cells. In addition, very low vitamin A levels would be undesirable explaining the essential role of vitamin A in epithelial and general cell maturation and function. However, the cytokine shifts associated with moderately low levels of vitamin A may be in some ways beneficial in an environment where HIV infection, M. tuberculosis infection, or other type 1 infections are highly prevalent and/or when acquired immunity is cooperated. In this review, we intend to describe the biochemical and immunological functions of retinoids against cancer.
Dermatologic Therapy, 2006
Retinoids are natural and synthetic vitamin A derivatives. They are lipophilic molecules and easily penetrate the epidermis. Their biologically active forms can modulate the expression of genes involved in cellular differentiation and proliferation. Retinoic acid (tretinoin), its 13-cis isomer isotretinoin, as well as various synthetic retinoids are used for therapeutic purposes, whereas retinaldehyde, retinol, and retinyl esters, because of their controlled conversion to retinoic acid or their direct receptor-independent biologic action, can be used as cosmeceuticals. These natural retinoic acid precursors are thus expected to be helpful in (i) renewing epidermal cells, (ii) acting as UV filters, (iii) preventing oxidative stress, (iv) controlling cutaneous bacterial flora, and (v) improving skin aging and photoaging. Retinol and retinyl esters are not irritant, whereas demonstrating only a modest clinical efficiency. On the other hand, retinaldehyde, which is fairly well tolerated, seems to be the most efficient cosmeceutical retinoid; it has significant efficiency toward oxidative stress, cutaneous bacterial flora, epidermis renewing, and photoaging.
The Use of Retinoids for the Prevention and Treatment of Skin Cancers: An Updated Review
International Journal of Molecular Sciences
Retinoids are natural and synthetic vitamin A derivatives that are effective for the prevention and the treatment of non-melanoma skin cancers (NMSC). NMSCs constitute a heterogenous group of non-melanocyte-derived skin cancers that impose substantial burdens on patients and healthcare systems. They include entities such as basal cell carcinoma and cutaneous squamous cell carcinoma (collectively called keratinocyte carcinomas), cutaneous lymphomas and Kaposi’s sarcoma among others. The retinoid signaling pathway plays influential roles in skin physiology and pathology. These compounds regulate diverse biological processes within the skin, including proliferation, differentiation, angiogenesis and immune regulation. Collectively, retinoids can suppress skin carcinogenesis. Both topical and systemic retinoids have been investigated in clinical trials as NMSC prophylactics and treatments. Desirable efficacy and tolerability in clinical trials have prompted health regulatory bodies to a...