BACKGROUND: Glucocorticoids are widely used for cancer patients, although they can reduce the efficacy of anticancer treatment. MATERIALS AND METHODS: We characterized non-apoptotic actions of glucocorticoids on tumor cell lines, primary tumor cells and an in vivo model, together with molecular signaling studies. RESULTS: Glucocorticoids enhanced cell proliferation in 9/17 cell lines and significantly promoted tumor cell proliferation in a pre-clinical mouse model of lung carcinoma. 65/139 primary acute childhood leukemia samples were glucocorticoid-resistant. Both dexamethasone and prednisolone increased in vitro survival in 21/65 samples from glucocorticoid-resistant primary leukemias, revealing a completely new action of glucocorticoids. Dexamethasone-induced proliferation was mediated by glucocorticoid receptor and activated the proliferation signaling pathways of protein kinase B/AKT and p38 mitogen-activated protein kinase. CONCLUSION: Our data suggest that restriction of the use of glucocorticoids during anticancer treatment might improve the outcome of patients with solid tumors.
BACKGROUND: Glucocorticoids are widely used for cancerpatients, although they can reduce the efficacy of anticancer treatment. MATERIALS AND METHODS: We characterized non-apoptotic actions of glucocorticoids on tumor cell lines, primary tumor cells and an in vivo model, together with molecular signaling studies. RESULTS: Glucocorticoids enhanced cell proliferation in 9/17 cell lines and significantly promoted tumor cell proliferation in a pre-clinical mouse model of lung carcinoma. 65/139 primary acute childhood leukemia samples were glucocorticoid-resistant. Both dexamethasone and prednisolone increased in vitro survival in 21/65 samples from glucocorticoid-resistant primary leukemias, revealing a completely new action of glucocorticoids. Dexamethasone-induced proliferation was mediated by glucocorticoid receptor and activated the proliferation signaling pathways of protein kinase B/AKT and p38 mitogen-activated protein kinase. CONCLUSION: Our data suggest that restriction of the use of glucocorticoids during anticancer treatment might improve the outcome of patients with solid tumors.
Authors: Shubha M Hegde; M Naveen Kumar; K Kavya; K M Kiran Kumar; Rashmi Nagesh; Rajeshwari H Patil; R L Babu; Govindarajan T Ramesh; S Chidananda Sharma Journal: Mol Cell Biochem Date: 2016-09-08 Impact factor: 3.396
Authors: L Lee Dupuis; Lillian Sung; Alexander Molassiotis; Andrea D Orsey; Wim Tissing; Marianne van de Wetering Journal: Support Care Cancer Date: 2016-08-26 Impact factor: 3.603
Authors: S Varadarajan; C Breda; J L Smalley; M Butterworth; S N Farrow; F Giorgini; G M Cohen Journal: Cell Death Differ Date: 2015-02-06 Impact factor: 15.828