RESUMO
BACKGROUND/AIM: The aberrant regulation of erythropoietin-producing hepatocellular carcinoma (EPH) receptors and ephrin ligands has been implicated in breast carcinoma, and artesunate has been shown to have anticancer effects. The aim of this study was to characterize the involvement of EPH receptors and ephrin ligands in mediating artesunate (ART)-induced growth suppression of normal breast cells and breast carcinoma cell lines. MATERIALS AND METHODS: The normal breast epithelial cells (MCF10A), non-invasive ductal breast carcinoma cells (MCF7), and invasive triple-negative breast carcinoma cells (MDA-MB-231) were grown in the absence or the presence of different concentrations of artesunate. The cells were counted, and total RNA was isolated. The abundance of transcripts corresponding to EPH receptors and ephrin ligands was determined by quantitative polymerase chain reaction. RESULTS: Cell viability was significantly reduced when cells were treated with artesunate, with MDA-MB-231 cells having the highest sensitivity. Artesunate had no significant effect on transcription of EPH/ephrins in MCF10A cells, but markedly increased EPHA8, EPHA10, EPHB6 and ephrin-A2 expression in MCF7 cells, and significantly increased EPHA3 and EPHA10 expression while reducing that of EPHA7 and ephrin-A3 in MDA-MB-231 cells. CONCLUSION: The relative changes in artesunate-treated MCF7 and MDA-MB-231 cells as compared to similarly treated MCF10A cells allow us to implicate combinatorial expression and receptor interactions for EPH receptor-mediated signal transduction that converges into pathways responsible for cell growth, proliferation, and apoptosis. Specifically, the alterations in EPHA7, EPHA8, EPHA10 and EPHB6 transcripts appear to be important participants in artesunate-mediated cellular effects.
Assuntos
Artesunato/farmacologia , Neoplasias da Mama/tratamento farmacológico , Carcinoma/tratamento farmacológico , Efrinas/metabolismo , Receptores da Família Eph/metabolismo , Apoptose/efeitos dos fármacos , Artesunato/uso terapêutico , Neoplasias da Mama/patologia , Carcinoma/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Ligantes , Células MCF-7 , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND/AIM: Breast cancer cell lines consist of bulk tumor cells and a small proportion of stem-like cells. While the bulk cells are known to express a distinct combination of Eph receptors and ephrin ligands, the transcript profiles of stem-like cells in these cell lines have not been adequately characterized. The aim of this study was to determine Eph receptor/ephrin ligand profiles of cancer stem cells specific to a triple negative breast carcinoma cell line. MATERIALS AND METHODS: The normal breast cell line MCF10A and the invasive breast carcinoma cell line MDA-MB-231 were used to isolate CD24+/CD24- cell populations. The profiles of Eph receptors and ephrin ligands were determined by real-time PCR and the relative abundance in bulk and stem cells were compared. RESULTS: Based on the mean ΔCT values, the descending order of abundance was as follows. Ephrin-A5 > EPHA2 > (EPHA8, EPHB2) > ephrin-B2 > (EPHA7, EPHB4, ephrin-A4) > ephrin-A3 > ephrin-A1 > (EPHB3, ephrin-B1) > EPHA4 > EPHA1 > EPHA10. EPHA6 and ephrin-A2 transcripts were not detectable in stem cells from either cell line. The expression of EPHA4, EPHA7, EPHA8, and ephrin-A5 in MDA-MB-231 stem cells was up-regulated by 12, 20, ~500, and 6.5-fold respectively. CONCLUSION: The up-regulation of transcripts for EPHA8 and its cognate ligand, ephrin-A5, in the stem cells isolated from MDA-MB-231, suggest their involvement in the invasiveness of this cell line. Based on literature reports, we propose the role of EPHA8 and ephrin-A5 in MDA-MB-231 stem cells via the PI3K-AKT-mTOR pathway.
Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Efrinas/metabolismo , Regulação Neoplásica da Expressão Gênica , Receptores da Família Eph/metabolismo , Células-Tronco/patologia , Mama/metabolismo , Neoplasias da Mama/metabolismo , Proliferação de Células , Células Cultivadas , Efrinas/genética , Feminino , Humanos , Invasividade Neoplásica , Receptores da Família Eph/genética , Células-Tronco/metabolismoRESUMO
Glutathione (GSH), often referred to as "the master antioxidant," participates not only in antioxidant defense systems, but many metabolic processes, and therefore its role cannot be overstated. GSH deficiency causes cellular risk for oxidative damage and thus as expected, GSH imbalance is observed in a wide range of pathological conditions including tuberculosis (TB), HIV, diabetes, cancer, and aging. Consequently, it is not surprising that GSH has attracted the attention of biological researchers and pharmacologists alike as a possible target for medical intervention. Here, we discuss the role GSH plays amongst these pathological conditions to illuminate how it can be used as a marker for human disease.
Assuntos
Glutationa/metabolismo , Estresse Oxidativo , Envelhecimento , Animais , Biomarcadores/análise , Biomarcadores/metabolismo , Diabetes Mellitus/metabolismo , Glutamato-Cisteína Ligase/metabolismo , Glutationa/análise , Infecções por HIV/metabolismo , Humanos , Neoplasias/metabolismo , Tuberculose/metabolismo , Vitamina D/metabolismoRESUMO
Cancer is a condition that has plagued humanity for thousands of years, with the first depictions dating back to ancient Egyptian times. However, not until recent decades have biological therapeutics been developed and refined enough to safely and effectively combat cancer. Three unique immunotherapies have gained traction in recent decades: adoptive T cell transfer, checkpoint inhibitors, and bivalent antibodies. Each has led to clinically approved therapies, as well as to therapies in preclinical and ongoing clinical trials. In this review, we outline the method by which these 3 immunotherapies function as well as any major immunotherapeutic drugs developed for treating a variety of cancers.
