RESUMEN
To investigate the mechanism underlying the effect of paeoniflorin (PF) on the proliferation and migration of psoriatic keratinocytes. The expressions of long noncoding RNA NEAT1, miR-3194-5p and Galectin-7 in skin tissues from psoriatic patients and healthy controls were detected. Psoriatic HaCat cells were used to investigate the function of NEAT1 and Galectin-7 as well as the effect and mechanism of PF in psoriasis. MTT, colony formation and scratch assays were used to assess the proliferation and migration of psoriatic HaCat cells. Dual-luciferase reporter assay was used to validate the interactions among NEAT1, miR-3194-5p and Galectin-7. NEAT1 and Galectin-7 were lowly expressed and miR-3194-5p was highly expressed in psoriatic patients. PF suppressed the proliferation and migration of psoriatic HaCat cells by elevating the expressions of NEAT1 and Galectin-7. NEAT1 positively mediated the expression of Galectin-7 by targeting miR-3194-5p. PF controls the proliferation and migration of psoriatic HaCat cells via the NEAT1/miR-3194-5p/Galectin-7 axis.
Asunto(s)
Galectinas/efectos de los fármacos , Glucósidos/farmacología , Queratinocitos/efectos de los fármacos , MicroARNs/efectos de los fármacos , Monoterpenos/farmacología , ARN Largo no Codificante/efectos de los fármacos , Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células HEK293 , Células HaCaT , Humanos , Psoriasis/patología , Transducción de Señal , Regulación hacia ArribaRESUMEN
This study identified chemotherapeutic agents that up-regulate programmed cell death ligand-1 (PD-L1) and galectin-9 (Gal-9) in breast cancer cells. Immunohistochemical (IHC) staining was used to evaluate changes in PD-L1 and Gal-9 expression in the tumor tissue of triple-negative breast cancer (TNBC) patients who received anthracycline- and taxane-based neoadjuvant chemotherapy. To determine whether PD-L1 and Gal-9 expression changes were attributable directly to chemotherapeutics, MDA-MB-231 cells and HS578T cells were treated with different concentrations of anthracycline and taxane. Expression levels of PD-L1 and Gal-9 were evaluated and the activation status of NFκB in MDA-MB-231 and HS578T cells was determined to identify the PD-L1 and Gal-9 up-regulation mechanism. Three cases of increased PD-L1 expression and two of increased Gal-9 expression were observed among the TNBC patients. PD-L1 and Gal-9 expression were up-regulated by anthracycline and taxane in MDA-MB-231 cells, but not in HS578T cells. Increased nuclear levels of NFκB were observed in MDA-MB-231 cells treated with 0.5 µM epirubicin. Anthracycline and taxane up-regulated PD-L1 and Gal-9 expression in some subtypes of TNBC. This study provides useful reference data for clinical trials investigating combination treatments with immune checkpoint inhibitors and chemotherapy.
Asunto(s)
Antineoplásicos/uso terapéutico , Antígeno B7-H1/biosíntesis , Galectinas/biosíntesis , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Adulto , Antraciclinas/uso terapéutico , Antígeno B7-H1/efectos de los fármacos , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Línea Celular Tumoral , Quimioterapia Adyuvante/métodos , Femenino , Galectinas/efectos de los fármacos , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Taxoides/uso terapéutico , Neoplasias de la Mama Triple Negativas/metabolismoRESUMEN
The formation of new blood vessels plays a crucial for the development and progression of pathophysiological changes associated with a variety of disorders, including carcinogenesis. Angiogenesis inhibitors (anti-angiogenics) are an important part of treatment for some types of cancer. Some natural products isolated from marine invertebrates have revealed antiangiogenic activities, which are diverse in structure and mechanisms of action. Many preclinical studies have generated new models for further modification and optimization of anti-angiogenic substances, and new information for mechanistic studies and new anti-cancer drug candidates for clinical practice. Moreover, in the last decade it has become apparent that galectins are important regulators of tumor angiogenesis, as well as microRNA. MicroRNAs have been validated to modulate endothelial cell migration or endothelial tube organization. In the present review we summarize the current knowledge regarding the role of marine-derived natural products, galectins and microRNAs in tumor angiogenesis.
Asunto(s)
Moduladores de la Angiogénesis/farmacología , Antineoplásicos/farmacología , Neoplasias/tratamiento farmacológico , Inhibidores de la Angiogénesis/farmacología , Animales , Productos Biológicos/farmacología , Galectinas/efectos de los fármacos , Humanos , Toxinas Marinas/farmacología , MicroARNs/efectos de los fármacosRESUMEN
Cells constantly adapt to external humoral cues like cytokines and hormones, but practically most cellular behavior is under locally guided control via cell-cell interactions. Galectins (Gals) are one of the most prominent members of the group of molecules involved in this intercellular signaling. They are the family of ß-galactoside specific lectins and consist of 15 different types, each with a specific function. They play crucial role in the immune system, inflammation, wound healing and carcinogenesis. In recent times, the role of Gals in the development of cardiovascular disease (CVD) has gained attention. Gals have been reported to act ambiguously by both relieving ischemia and accelerating atherosclerosis. Atherosclerosis can ultimately lead to myocardial infarction or ischemic stroke, which are both associated with Gals. There is also a role for Gals in the development of myocarditis by their influence on inflammatory processes. Moreover, Gal acts as a biomarker for the severity of myocardial ischemia and heart failure (HF). This review summarizes the association between Gals and the development and pathogenesis of CVD like atherosclerosis, stroke, myocardial infarction, and HF. A comprehensive outline of the association between Gals and more general mechanisms such as angiogenesis, arteriogenesis and atherosclerosis has also been provided. Modulation of Gal signaling holds great promise for the treatment of CVD as evident from preclinical studies.
Asunto(s)
Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/fisiopatología , Galectinas/efectos de los fármacos , Galectinas/fisiología , Animales , Aterosclerosis/tratamiento farmacológico , Humanos , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/fisiopatología , Neovascularización Fisiológica/efectos de los fármacosRESUMEN
Conformational analysis of champedak galactose-binding (CGB) lectin under different urea concentrations was studied in phosphate-buffered saline (pH 7.2) using far-ultraviolet circular dichroism (far-UV CD), tryptophan (Trp) fluorescence and ANS fluorescence. In all cases, CGB lectin displayed a two-step, three-state transition. The first transition (from the native state to the intermediate state) started at â¼2.0 M urea and ended at â¼4.5 M urea, while the second transition (from the intermediate state to the completely denatured state) was characterized by the start- and end-points at â¼5.75 M and â¼7.5 M urea, respectively, when analyzed by the emission maximum of Trp fluorescence. A marked increase in the Trp fluorescence, ANS fluorescence and -CD values at 218 nm (-CD218 nm) represented the first transition, whereas a decrease in these parameters defined the second transition. On the other hand, emission maximum of the Trp fluorescence showed a continuous increase throughout the urea concentration range. Transformation of tetramer into monomer represented the first transition, whereas the second transition reflected the unfolding of monomer. Far-UV CD, Trp fluorescence and ANS fluorescence spectra were used to characterize the native, the intermediate and the completely denatured states of CGB lectin, obtained at 0.0 M, 5.0 M and 9.0 M urea, respectively. The intermediate state was characterized by the presence of higher secondary structures, increased ANS binding as well as increased Trp fluorescence intensity. A gradual decrease in the hemagglutination activity of CGB lectin was observed with increasing urea concentrations, showing complete loss at 4.0 M urea.
Asunto(s)
Artocarpus/química , Galectinas/química , Urea/farmacología , Dicroismo Circular , Fluorescencia , Galectinas/efectos de los fármacos , Hemaglutinación , Concentración de Iones de Hidrógeno , Conformación Proteica/efectos de los fármacos , Pliegue de Proteína/efectos de los fármacos , Estructura Secundaria de Proteína/efectos de los fármacos , Espectrometría de FluorescenciaRESUMEN
Galectins are emerging as a family of proteins that play an important role in several steps of tumorigenesis. Evidence is accumulating that galectins are expressed by the tumor endothelium, where they contribute to different steps of tumor progression such as immune escape and metastasis. Recent studies have identified an important role for galectins in tumor angiogenesis. Moreover, it has been shown that galectins in the endothelium can be targeted for therapeutic applications. This opens a window of opportunity for the development of tumor-type independent treatment strategies. This review focuses on the expression of galectins in the tumor endothelium, their contribution to tumor progression, and their application in tumor-type independent cancer therapy.
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Endotelio Vascular/metabolismo , Galectinas/metabolismo , Neoplasias/irrigación sanguínea , Neoplasias/metabolismo , Neovascularización Patológica/metabolismo , Animales , Antineoplásicos/uso terapéutico , Endotelio Vascular/efectos de los fármacos , Galectinas/efectos de los fármacos , Humanos , Neoplasias/tratamiento farmacológico , Neovascularización Patológica/tratamiento farmacológicoRESUMEN
BACKGROUND: Galectin-9 is involved in chemotaxis and adhesion of eosinophils, and is induced in vascular endothelial cells by interferon-gamma (IFN-gamma). 15-deoxy-delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is a ligand for peroxisome proliferator-activated receptor-gamma (PPAR-gamma), and known to modulate the expression of various genes. METHODS: We have studied the effect of 15d-PGJ(2) on the IFN-gamma-induced galectin-9 expression in human umbilical vein endothelial cells (HUVEC) in culture. RESULTS: 15d-PGJ(2) inhibited the IFN-gamma-induced galectin-9 expression in a PPAR-gamma-independent manner, and also inhibited the adhesion of EoL-1 cells to an HUVEC monolayer treated with IFN-gamma. 15d-PGJ(2) partially inhibited IFN-gamma-induced phosphorylation of STAT-1 in HUVEC. CONCLUSIONS: 15d-PGJ(2) may regulate inflammatory reactions through the inhibition of galectin-9 expression.
Asunto(s)
Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Galectinas/biosíntesis , Galectinas/efectos de los fármacos , Factores Inmunológicos/farmacología , Interferón gamma/farmacología , Prostaglandina D2/farmacología , Venas Umbilicales/citología , Venas Umbilicales/metabolismo , Western Blotting , Adhesión Celular/efectos de los fármacos , Células Cultivadas/efectos de los fármacos , Proteínas de Unión al ADN/efectos de los fármacos , Proteínas de Unión al ADN/metabolismo , Relación Dosis-Respuesta a Droga , Endotelio Vascular/efectos de los fármacos , Humanos , Factores Inmunológicos/administración & dosificación , Interferón gamma/administración & dosificación , Fosforilación/efectos de los fármacos , Reacción en Cadena de la Polimerasa , Prostaglandina D2/administración & dosificación , Prostaglandina D2/análogos & derivados , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Receptores Citoplasmáticos y Nucleares/administración & dosificación , Receptores Citoplasmáticos y Nucleares/antagonistas & inhibidores , Factor de Transcripción STAT1 , Transactivadores/efectos de los fármacos , Transactivadores/metabolismo , Factores de Transcripción/administración & dosificación , Factores de Transcripción/antagonistas & inhibidores , Transcripción Genética/efectos de los fármacos , Venas Umbilicales/efectos de los fármacosRESUMEN
A lectin from cat liver has been identified and purified by affinity chromatography on asialofetuin-Sepharose. One hundred micrograms of lectin was obtained from one cat liver with a purification factor of 1561. The lectin agglutinates trypsin-treated rabbit and cow erythrocytes. Hemagglutination was inhibited only by saccharides containing -galactosyl residues, of which the 1-amine-1-deoxy- -D-galactose was the most potent one by inhibiting hemagglutination at a concentration of 12.5 mM, followed by melibiose, trehalose and galactose. The lectin has a subunit molecular mass of 14.4 kDa determined by SDS-PAGE under reducing conditions and a pI of 4.85. Compared with the composition of lectins from calf heart and porcine heart, cat liver lectin contains approximately the same amount of cysteine, half the amount of glycine, twice as much arginine and threonine, and three times the amounts of tyrosine and methionine. Cat liver lectin contains four cysteine residues per subunit, all of them in the reduced form. Their lack of reactivity towards thiol-reactive supports suggests they are not exposed on the lectin surface. The protein apparently has a blocked N-terminus. The purified lectin was stable for up to 20 months stored at +4 C in buffer supplemented with 4 mM -mercaptoethanol. Results indicated that this lectin belongs to the family of soluble -galactoside-binding lectins, also known as galectins, which are expressed in a wide range of vertebrate tissues.