Search Results (14)

Background/Objectives: Retinoic acid has been shown to inhibit melanoma progression; however, its underlying mechanisms remain unclear. In this study, we investigated the role of the retinoic acid-inducible gene TIG3 in regulating melanoma cell growth, as well as elucidating its involvement in apoptosis. Methods: The expression of TIG3 in melanoma tissues was analyzed using a cDNA microarray. Cell viability and cell death were measured using the WST-1 and LDH assay kits, respectively. The gene expression changes that were induced by TIG3 were identified through RNA sequencing, while apoptosis-related pathways were examined using a human apoptosis protein array. The protein expression levels were further validated using Western blot analysis. Results: TIG3 expression was significantly downregulated in melanoma tissues. The overexpression of TIG3 in melanoma cells led to reduced cell viability and increased cell death. TIG3 suppressed the expression of several apoptosis-regulating proteins, including PON2, Fas, cIAP-1, Claspin, Clusterin, HTRA2, and Livin, while promoting the expression of cleaved Caspase-3. Supplementation with cIAP-1, HTRA2, or Livin partially reversed TIG3-induced Caspase-3 expression and cell death. Conclusions: Our findings suggest that TIG3 may contribute to the anti-melanoma effects of retinoic acid, with IAP family proteins playing a key role in the TIG3-mediated regulation of melanoma cell survival. Full article

Tazarotene, a retinoid derivative, is widely used in treating skin conditions such as psoriasis and acne. Recent studies have demonstrated its potential as a promising therapeutic agent for treating melanoma in situ. Its primary mechanism of action involves the selective activation of retinoic acid receptors (RAR-β and RAR-γ), which play important roles in regulating cell growth, differentiation, and apoptosis. By activating these receptors, tazarotene influences the expression of several downstream inducible genes, such as tazarotene-induced gene-1 (TIG1), TIG2, and TIG3. These genes play crucial roles in regulating melanoma cell proliferation, invasiveness, and immune responses in the tumor microenvironment. This review aims to provide a comprehensive overview of the current status of retinoid derivatives—particularly tazarotene—in melanoma treatment and the latest research regarding their molecular mechanisms. We will explore how tazarotene suppresses melanoma growth through gene regulation mechanisms and discuss its potential role in immune responses within the tumor microenvironment. Additionally, we assess the advantages and challenges of using tazarotene as a topical treatment and explore its future clinical applications. These studies contribute to a wider understanding of tazarotene’s antitumor mechanisms, providing a solid theoretical foundation for its potential as a therapeutic option for melanoma in situ. Full article

Candida albicans (C. albicans) is the most common pathogen responsible for a wide spectrum of human infections ranging from superficial mucocutaneous mycoses to systemic life-threatening diseases. Its main virulence factors are the morphological transition between yeast and hyphal forms and the ability to produce biofilm. Novel antifungal strategies are required given the severity of systemic candidiasis, especially in immunocompromised patients, and the lack of effective anti-biofilm treatments. We previously demonstrated that all-trans retinoic acid (ATRA), an active metabolite of vitamin A, exerted an inhibitory effect on Candida growth, yeast–hyphal transition and biofilm formation. Here, we further investigated the possible anti-Candida potential of trifarotene and tazarotene, which are the other two molecules belonging to the retinoid family, compared to ATRA. The results indicate that both drugs were able to suppress Candida growth, germination and biofilm production, although trifarotene was proven to be more effective than tazarotene, showing effectiveness comparable to ATRA. In silico studies suggest that all three retinoids may exert antifungal activity through their molecular interactions with the heat shock protein (Hsp) 90 and 14α-demethylase of C. albicans. Moreover, interactions between retinoids and ergosterol have been observed, suggesting that those compounds have great potential against C. albicans infections. Full article

Exploring tazarotene, a third-generation retinoid for potential hand osteoarthritis treatment, this study presents the development and validation of an ultra-performance liquid chromatography with quadrupole detector mass spectrometry (UPLC-QDa) method for the simultaneous quantification of tazarotene and tazarotenic acid, its active metabolite, in porcine skin. Method development involved a design-of-experiments approach for chromatographic optimization of gradient steepness, organic solvent volume, column temperature, capillary voltage, flow rate, and cone voltage. Central composite orthogonal design was used to optimize peak area, peak width, retention time, and resolution. Validation was performed in accordance with U.S. Food and Drug Administration guidelines. The method was linear over the concentration range of 0.4–18,750 ng/mL for tazarotene and 13.3–12,500 ng/mL for tazarotenic acid, with r² values of ≥0.99. Chromatographic analysis demonstrated acceptable accuracy and precision (<15%), and stability tests confirmed the analytes’ stability under various conditions. This validated method offers a reliable and accurate approach for the simultaneous analysis of tazarotene and tazarotenic acid, facilitating further research into their therapeutic applications for hand osteoarthritis. Full article

Retinoid-based drugs, while effective, are associated with systemic toxicity. Topical alternatives offer a safer option, and tazarotene, a third-generation synthetic retinoid, holds promise. This study investigates tazarotene’s transdermal delivery potential, focusing on its application for joint-related conditions. The aim of this study was to investigate the suitability of tazarotene as a candidate for transdermal delivery into joints. In vitro permeation studies, using porcine skin, assessed tazarotene’s transdermal drug delivery from solution and gel formulations. A tape-stripping analysis determined stratum corneum retention and a pilot study using porcine joints assessed tazarotene’s ability to reach articular cartilage. Ultra Performance Liquid Chromatography coupled with a mass detector method was used to quantify tazarotene and tazarotenic acid permeation. The results validate that tazarotene can permeate porcine skin and accumulate in articular cartilage in detectable amounts. The detection of tazarotene and tazarotenic acid in both the in vitro permeation studies and the pilot study on porcine joints validate the drug’s potential therapeutic use for hand osteoarthritis. This study lays the groundwork for future research, contributing insights into tazarotene’s potential for transdermal drug delivery and guiding further exploration in topical retinoid applications. Full article

A skin ailment known as psoriasis, which affects 2–5% of people worldwide, is characterised by excessive keratinocyte proliferation and abnormal differentiation. Calcipotriene, a synthetic vitamin D analogue, is the first-line treatment for psoriasis. It may be used in combination with methotrexate, tazarotene, acitretin, cyclosporine, and corticosteroids. It reduces the number of T cells and regulates the inflammatory response in psoriatic lesions. However, the effectiveness of pharmacotherapy based on conventional formulations for treating patients is only partially favourable. Recent developments in nanotechnology-based nanomedicines may allow us to improve the efficacy and safety of pharmacotherapeutic treatments for psoriasis. Enhancing therapeutic efficacy while lowering toxicity through overall dose reduction are two spectacular effects of using nanomedicine as a medication carrier. This novel method efficiently ensures the site-specific administration of medications throughout the skin to treat psoriatic lesions. The present manuscript aims to discuss the chemistry and pharmacology of calcipotriene, conventional pharmacotherapy and contemporary research on calcipotriene, and the combinations of it that are used as nanomedicines for the better management of psoriasis. This review primarily focuses on the nanoemulsion loaded gel of calcipotriene and clobitasol propionate as it offers high drug loading and retention in the skin, improving the local concentration of both drugs and reducing their systemic side effects. Calcipotriene and methotrexate combined in a nanostructured lipid carrier are also the most recent generation of solid lipid nanoparticles, with better drug loading, controlled release, and enhanced bioavailability. Full article

Electrospun polycaprolactone nanofibers with embedded magnetic nanoparticles were developed for use in the topical delivery of antipsoriatic drugs. To test a hydrophobic drug, a tazarotene has been used, which is an efficient retinoid derivative. Such a smart hyperthermia nanofiber system with self-generated heat from the incorporated magnetic nanoparticles induced drug release in response to on–off switching of alternating magnetic fields for the delivery of tazarotene through the skin, as quantified using Franz cells. This highly efficient external field-controllable system with minimal skin irritation could create a new avenue for the topical therapy of psoriasis. Full article

Chemerin is protective in experimental models of hepatocellular carcinoma (HCC). Noteworthy, chemerin mRNA and protein were reduced in HCC tissues of Asian patients with mostly hepatitis B disease etiology. The current study nevertheless showed that chemerin protein was induced in tumor tissues of European HCC patients with non-alcoholic fatty liver disease (NAFLD) and patients with unclear disease etiology. A similar regulation was observed in hepatitis B virus (HBV), but not in hepatitis C virus (HCV), related HCC. The apparent discrepancy between the regulation of chemerin in HBV-HCC obtained from our study and recent reports led us to use the chemerin antibodies applied in the previous assays. These antibodies could not equally detect different chemerin isoforms, which were overexpressed in HepG2 cells. Higher chemerin protein in HCC was nevertheless confirmed by the use of all antibodies. Chemerin protein was low in Huh7 and PLC/PRF/5 cells whereas HepG2 and Hep3B cells had chemerin protein similar as primary human hepatocytes. Besides, the anti-tumor effects of retinoids in hepatocyte cell lines did not enclose upregulation of chemerin, which was initially discovered as a tazarotene induced protein in the skin. Finally, protein levels of the chemerin receptor, chemokine-like receptor 1 (CMKLR1), declined in non-viral, and tended to be lower in HBV-HCC tissues suggesting reduced chemerin activity in the tumors. To sum up, our work showed an opposite regulation of chemerin and CMKLR1 in NAFLD and HBV associated HCC. In HCV-HCC neither chemerin nor its receptor were changed in the tumor tissues. Current findings do not support a critical role of total chemerin protein levels in HCC of non-viral and viral etiology. Accordingly, tumor-localized chemerin protein was not associated with tumor-node-metastasis classification. Full article

Exposure of a drug to UV irradiation could affect its physicochemical properties. Hence, photostability testing is essential for topically administered drugs. Tazarotene, a receptor-selective, third-generation retinoid, is commonly used to treat acne vulgaris and psoriasis. In the present study, an in-depth analysis of the photostability of tazarotene in ethanolic solution in the presence of zinc oxide and/or titanium dioxide as well as benzophenone-type UV filters was performed. Eleven presumed products were derived from the photocatalytic degradation of tazarotene using ultra-performance liquid chromatography–tandem mass spectrometry, and transformation pathways were proposed. The degradation process mainly affected the 4,4-dimethyl-3,4-dihydro-2H-thiopyran moiety. The fragments most susceptible to oxidation were the methyl groups and the sulfur atom. Moreover, in the presence of sulisobenzone, under UV irradiation, tazarotene was subjected to a degradation process, which resulted in two photodecomposition products. In silico studies performed by OSIRIS Property Explorer demonstrated that five of the degradation products could be harmful in terms of the reproductive effects, which are associated with 3,4-dihydro-6-methyl-2H-1-benzothiopyran 1,1-dioxide, while one of them demonstrated potential irritant activity. The cytotoxic properties of the degradation products of tazarotene were assessed by MTT assay on a panel of human adherent cancer cells. Time- and concentration-dependent growth inhibition was evidenced in ovary (A2780) and breast (MDA-MB-231) cancer cell lines. The potential implication of the outcomes of the present research requires further studies mainly concerning the photostability of tazarotene in the topical formulations. Full article

Almost every organism has the ability of repairing damaged tissues or replacing lost and worn out body parts, nevertheless the degree of the response substantially differs between each species. Adult sea cucumbers from the Holothuria glaberrima species can eviscerate various organs and the intestinal system is the first one to regenerate. This process involves the formation of a blastema-like structure that derives from the torn mesentery edges by the intervention of specific cellular processes (e.g., cell dedifferentiation and division). Still, the genetic networks controlling the regenerative response in this model system are just starting to be unraveled. In this work we examined if and how the retinoic acid (RA) signaling pathway is involved in the regenerative response of this deuterostome. We first identified and characterized the holothurian orthologs for short chain dehydrogenase/reductase 7 (SDR7) and aldehyde dehydrogenase family 8A1 (ALDH8A1), two enzymes respectively associated with retinaldehyde and RA anabolism. We then showed that the SDR7 transcript was differentially expressed during specific stages of intestinal regeneration while ALDH8A1 did not show significant differences in regenerating tissues when compared to those of normal (non-eviscerated) organisms. Finally, we investigated the consequences of modulating RA signaling during intestinal regeneration using pharmacological tools. We showed that application of an inhibitor (citral) of the enzyme synthesizing RA or a retinoic acid receptor (RAR) antagonist (LE135) resulted in organisms with a significantly smaller intestinal rudiment when compared to those treated with DMSO (vehicle). The two inhibitors caused a reduction in cell division and cell dedifferentiation in the new regenerate when compared to organisms treated with DMSO. Results of treatment with tazarotene (an RAR agonist) were not significantly different from the control. Taken together, these results suggest that the RA signaling pathway is regulating the cellular processes that are crucial for intestinal regeneration to occur. Thus, RA might be playing a role in echinoderm regeneration that is similar to what has been described in other animal systems. Full article

Psoriasis is an inflammatory skin disease characterized by the presence of whitish and scaly plaques, which can cover up to 90% of the body surface. These plaques result from the hyperproliferation and abnormal differentiation of keratinocytes. Dermopharmaceutical testing of new therapies is limited by healthy and pathological skin models, which are not closely enough mimicking their in vivo counterparts. In this study, we exploited percutaneous absorption and Ultra Performance Liquid Chromatography (UPLC) analyses in order to determine the metabolic capacity of our psoriatic skin model. Skin substitutes were reconstructed according to the self-assembly method and tested regarding their percutaneous absorption of a topical formulation of tazarotene, followed by UPLC analyses. Histological and immunofluorescence analyses confirmed both the healthy and psoriatic phenotypes. Results from percutaneous absorption showed a significant level of tazarotene metabolite (tazarotenic acid) when the formulation was applied over 24 h on the skin substitutes. The presence of tazarotenic acid in the dermis and the epidermis of healthy and psoriatic skin substitutes confirms the metabolic capacity of both skin models, and thereby their ability to screen new molecules with antipsoriatic potential. In conclusion, the present data suggest that our psoriatic skin model could possibly be used in clinic to screen in vitro responses of patient to a panel of drugs without having them experiencing the drawback of each drug. Full article

Acne vulgaris is a common inflammatory pilosebaceous condition that affects 80–90% of adolescents. Since the introduction of tretinoin over 40 years ago, topical retinoid products have been a mainstay of acne treatment. The retinoids are very effective in addressing multiple aspects of the acne pathology as they are comedolytic and anti-inflammatory, and do not contribute to antibiotic resistance or microbiome disturbance that can be associated with long-term antibiotic therapies that are a common alternative treatment. However, topical retinoids are associated with skin dryness, erythema and pain, and may exacerbate dermatitis or eczema. Thus, there is a clear need to target delivery of the retinoids to the pilosebaceous units to increase efficacy and minimise side effects in surrounding skin tissue. This paper reviews the current marketed topical retinoid products and the research that has been applied to the development of targeted topical delivery systems of retinoids for acne. Full article

Chemerin (also known as tazarotene-induced gene 2 and retinoic acid receptor responder 2) has been identified as an adipokine that exerts effects on many biological processes, including adipogenesis, angiogenesis, inflammation, immune responses, and food intake. This variety of effects has led to its implication in obesity and co-morbidities including diabetes and a risk of cardiovascular disease. The biological effects are mostly mediated by a so-called G protein-coupled receptor, chemokine-like receptor 1 (CMKLR1). Given the association of chemerin with obesity and related diseases, we decided to study in detail the regulation of chemerin and CMKLR1 expression in white adipose tissue (WAT). Specifically, we focused on their expression levels in physiological and pathophysiological settings involved in energy balance: e.g., fasting, postnatal development, and gender. We used Sprague Dawley rats with different nutritional statuses, levels of hormonal deficiency, and states of development as well as ob/ob (leptin-deficient) mice. We analysed the protein expression of both the ligand and receptor (chemerin and CMKLR1) in gonadal WAT by western blotting. We found that chemerin and CMKLR1 protein levels were regulated in WAT by different conditions associated with metabolic changes such as nutritional status, sex steroids, pregnancy, and food composition. Our data indicate that regulation of the expression of this new adipokine and its receptor by nutritional status and gonadal hormones may be a part of the adaptive mechanisms related to altered fat mass and its metabolic complications. Full article

A stability-indicating RP-HPLC method has been developed and validated for the simultaneous determination of phenoxyethanol (PE), methylparaben (MP), propylparaben (PP), mometasone furoate (MF), and tazarotene (TA) in topical pharmaceutical dosage formulation. The desired chromatographic separation was achieved on the Waters X-Bridge^TM C18 (50×4.6mm, 3.5μ) column using gradient elution at 256 nm detection wavelength. The optimized mobile phase consisted of 0.1%v/v orthophosphoric acid in water as solvent-A and acetonitrile as solvent-B. The method showed linearity over the range of 5.88–61.76 μg/mL, 0.18–62.36 μg/mL, 0.17–6.26 μg/mL, 0.47–31.22 μg/mL, and 0.44–30.45 μg/mL for PE, MP, PP, MF, and TA, respectively. The recovery for all of the components was in the range of 98-102%. The stability-indicating capability of the developed method was established by analysing the forced degradation samples, in which the spectral purity of PE, MP, PP, MF, and TA along with the separation of degradation products from the analyte peaks was achieved. The proposed method was successfully applied for the quantitative determination of PE, MP, PP, MF, and TA in a cream sample. Full article