RESUMEN
BACKGROUND: The serum and glucocorticoid-induced kinase-1 (SGK1) belonging to the AGC protein kinase family phosphorylates serine and threonine residues of target proteins. It regulates numerous ion channels and transporters and promotes survival under cellular stress. Unique to SGK1 is a tight control at transcriptional and post-transcriptional levels. SGK1 regulates multiple signal transduction pathways related to tumor development. Several studies have reported that SGK1 is upregulated in different types of human malignancies and induces resistance against inhibitors, drugs, and targeted therapies. RESULTS AND CONCLUSION: This review highlights the cellular functions of SGK1, its crucial role in cancer development, and clinical insights for SGK1 targeted therapies. Furthermore, the role of SGK1-mediated autophagy as a potential therapeutic target for cancer has been discussed.
Asunto(s)
Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Autofagia/efectos de los fármacos , Carcinogénesis/metabolismo , Proteínas Inmediatas-Precoces/metabolismo , Terapia Molecular Dirigida/métodos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Biomarcadores de Tumor/antagonistas & inhibidores , Biomarcadores de Tumor/metabolismo , Carcinogénesis/efectos de los fármacos , Carcinogénesis/genética , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Humanos , Proteínas Inmediatas-Precoces/antagonistas & inhibidores , Proteínas Inmediatas-Precoces/genética , Neoplasias/diagnóstico , Neoplasias/genética , Oncogenes , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/genética , Activación Transcripcional , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/genéticaRESUMEN
This study aimed to design and evaluate enhanced permeation and retention (EPR)-mediated anticancer effect of polymer-modified and drug-loaded magnetite nanocomposites. The preformulated bare (10 nm), chitosan-superparamagnetic iron oxide (SPIO; 69 nm), heparin-SPIO (42 nm), and (3-aminopropyl)triethoxysilane-polyethylene glycol-SPIO (17 nm) nanocomposites were utilized to evaluate the EPR-mediated localized cancer targeting and retention of doxorubicin (DOX) and paclitaxel (PTX) in human ovarian cancer cell lines, A2780 and OVCAR-3 in vitro and in the tumor-baring Balb/c mice in vivo. Fluorescence microscopy showed that DOX- and PTX-loaded SPIO nanoparticles caused long-term accumulation and cytoplasmic retention in A2780 and OVCAR-3 cells, as compared to free drugs in vitro. In vivo antiproliferative effect of present formulations on immunodeficient female Balb/c mice showed a tremendous amount of ovarian tumor shrinkage within 6 weeks. The present nanocomposite systems of targeted drug delivery proved to be efficient drug carrier with sustained drug release and long-term retention with enhanced cytotoxic properties in vitro and in vivo.
Asunto(s)
Antineoplásicos/farmacología , Doxorrubicina/farmacología , Portadores de Fármacos/administración & dosificación , Nanopartículas de Magnetita/administración & dosificación , Neoplasias Ováricas/tratamiento farmacológico , Animales , Línea Celular Tumoral , Quitosano/química , Femenino , Humanos , Ratones Endogámicos BALB C , Ratones SCID , Polietilenglicoles/química , Propilaminas/química , Silanos/químicaRESUMEN
Amounts of DNA damage and homocysteine (Hcy) in heart patients blood may have strong function in the causation of cardiovascular disease (CVD). The main objective of this work was to know experimentally the role of total oxidants (produced by Reactive Oxygen species (ROS), clinical biochemical indices, their oxidized products and total antioxidant status (TAS) among such patients to find the association of homocysteine, total oxidation status (TOS) and oxidative DNA damage with other clinical parameters in sixty positive CVD patients compared with those of 60 normal subjects. As compared to healthy individuals, CVD patients had significantly higher concentrations of homocysteine (p<0.0001), total oxidants stress (TOS) (p<0.0001), serum total lipids (p<0.04), malondialdehyde (MDA) (p<0.001), high density lipoprotein-cholesterol (HDL-C) (p<0.0001), and low density lipoprotein cholesterol (LDL-C) (p<0.01), than those of healthy individuals. Plasma Hcy content, TOS and amount of DNA were positively and significantly associated with cholesterol, triglycerides, systolic blood pressure, urea, and albumin (p values<0.01). TOS, Hcy and oxidative DNA damage were negatively correlated with HDL-c, TAS and proteins. It is suggested that these parameters have pivotal role in diagnostic process of determining severity in CAD patients. Oxidized products of macromolecules in blood of CVD patients impart major functions in causing CVD disease.