1. Epinephrine protects cancer cells from apoptosis via activation of cAMP-dependent protein kinase and BAD phosphorylation.
- Author
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Sastry KS, Karpova Y, Prokopovich S, Smith AJ, Essau B, Gersappe A, Carson JP, Weber MJ, Register TC, Chen YQ, Penn RB, and Kulik G
- Subjects
- Breast Neoplasms metabolism, Cell Line, Tumor, Enzyme Activation, Humans, Male, Models, Biological, Phosphorylation, Prostatic Neoplasms metabolism, Signal Transduction, Adrenergic Agonists pharmacology, Apoptosis, Breast Neoplasms pathology, Cyclic AMP-Dependent Protein Kinases metabolism, Epinephrine pharmacology, Gene Expression Regulation, Neoplastic, Prostatic Neoplasms pathology, bcl-Associated Death Protein metabolism
- Abstract
The stress hormone epinephrine is known to elicit multiple systemic effects that include changes in cardiovascular parameters and immune responses. However, information about its direct action on cancer cells is limited. Here we provide evidence that epinephrine reduces sensitivity of cancer cells to apoptosis through interaction with beta(2)-adrenergic receptors. The antiapoptotic mechanism of epinephrine primarily involves phosphorylation and inactivation of the proapoptotic protein BAD by cAMP-dependent protein kinase. Moreover, BAD phosphorylation was observed at epinephrine concentrations found after acute and chronic psychosocial stress. Antiapoptotic signaling by epinephrine could be one of the mechanisms by which stress promotes tumorigenesis and decreases the efficacy of anti-cancer therapies. more...
- Published
- 2007
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