Abstract
ABSTRACTThe stress responses in human body lead to secretion of cortisol hormone. The present study investigated the cellular responses on cell growth and cellular differentiation into adipocytes by exposure of synthetic stress hormone, dexamethasone (DEX) in various human cancer and normal cells. After prolonged exposure of cells with 1 μg/ml DEX for 2 weeks, population doubling time (PDT) was significantly (P < .05) increased by inhibited cell growth in A-549 and MCF-7 cancer cells, and was unchanged in MDA-MB-231 cancer cells, normal MRC-5 fibroblasts, umbilical cord matrix-derived mesenchymal stem cells (UCMSCs) and dental papilla tissue-derived mesenchymal stem cells (DSCs). Whereas, PDT was significantly (P < .05) decreased in U87-MG cancer cells by increased cell growth. Glucose uptake was significantly (P < .05) increased in all the cancer cell lines compared to that in normal cell lines. Further, adiposome-like vesicles were noted in A-549 and MCF-7 cancer cells indicating retarded cell growth by DEX treatment, and the vesicles were stained with Oil-Red O solution. Further, the expression of adipocyte-specific genes such as glucose transporter type 4 (GLUT4), glucocorticoid receptors β (GRβ) and peroxisome proliferator-activated receptor γ (PPARγ) were significantly (P < .05) increased in A-549 and MCF-7 with lipid vesicles. The level of telomerase activity was found to be significantly (P < .05) downregulated in DEX-treated A-549 and MCF-7 cancer cells. Our results have clearly shown that DEX treatment induces inhibition of cell growth by differentiating into adipocyte-like cells in dexamethasone sensitive cancer cells.
Highlights
The secretion of adrenocorticotropic hormone by the anterior pituitary gland is stimulated under stress conditions, and this further increase the secretion of glucocorticoids (GCs) often referred to as corticosteroids from the adrenal gland of almost every vertebrate, including human
After prolongedly exposure with 1 μg/ml DEX for 2 weeks, the population doubling time (PDT) was significantly (P < .05) increased in A-549 and MCF-7 cancer cells, and PDT was not changed in MDAMB-231 cancer cells, MRC-5 fibroblasts, umbilical cord matrix-derived mesenchymal stem cells (UCMSCs) and dental papilla tissuederived mesenchymal stem cells (DSCs)
The prolonged exposure to 1 μg/ ml (∼0.25 μM) of DEX induced the inhibition of cell growth in cancer cell lines, such as A-549 and MCF-7 cancer cells
Summary
The secretion of adrenocorticotropic hormone by the anterior pituitary gland is stimulated under stress conditions, and this further increase the secretion of glucocorticoids (GCs) often referred to as corticosteroids from the adrenal gland of almost every vertebrate, including human. The main function of secreted GCs in response to the stress condition is to increase the concentration of blood glucose by stimulating gluconeogenesis resulting in the synthesis of glucose from nonglucose carbohydrate, and through the breakdown of amino acids and lipids (Munck et al 1984). GCs combined with their receptor (GR) play a major role in the anti-inflammatory response of cells through transcriptional regulation (Busillo and Cidlowski 2013). It has been demonstrated that lymphocyte proliferation, such as T-cells, is inhibited by decreased production of T cell growth factor which play a role in the production and development of the T-cells (Arya et al 1984). GCs induces the decreased secretion of several types of interferons and interleukins which are responsible for the interactions and communications between immune cells (Kunicka et al 1993). The inhibition of cell growth and induction of apoptotic cell death are observed in several type of cancer cells after being
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
