Glucocorticoid-mediated apoptosis resistance of solid tumors.
More than a quarter of a century ago, the phenomenon of glucocorticoid-induced apoptosis in the majority of hematological cells was first recognized. More recently, glucocorticoid-induced antiapoptotic signaling associated with apoptosis resistance towards cytotoxic therapy has been identified in cells of epithelial origin, most of malignant solid tumors and some other tissues. Despite these huge amounts of data demonstrating differential pro- and anti-apoptotic effects of glucocorticoids, the underlying mechanisms of cell type-specific glucocorticoid signaling are just beginning to be described. This review summarizes our present understanding of cell type-specific pro- and anti-apoptotic signaling induced by glucocorticoids. We shortly introduce mechanisms of glucocorticoid resistance of hematological cells. We highlight and discuss the emerging molecular evidence of a general induction of survival signaling in epithelial cells and carcinoma cells by glucocorticoids. We give a summary of our current knowledge of decreased proliferation rates in response to glucocorticoid pre- and combination treatment, which are suspicious to be involved not only in protection of normal tissues, but also in protection of solid tumors from cytotoxic effects of anticancer agents.
Herr
Ingrid
I
Department of Surgery, University of Heidelberg, Germany. i.herr@dkfz.de
Büchler
Markus W
MW
Mattern
Jürgen
J
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D005938:Glucocorticoids