title: Epinephrine protects cancer cells from apoptosis via activation of cAMP-dependent protein kinase and BAD phosphorylation.
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.
authors.affiliation: Department of Cancer Biology, Section on Comparative Medicine, and Center for Human Genomics, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA.
authors.forename: Konduru S R
authors.initials: KS
authors.lastname: Sastry
authors.forename: Yelena
authors.initials: Y
authors.lastname: Karpova
authors.forename: Sergey
authors.initials: S
authors.lastname: Prokopovich
authors.forename: Adrienne J
authors.initials: AJ
authors.lastname: Smith
authors.forename: Brian
authors.initials: B
authors.lastname: Essau
authors.forename: Avynash
authors.initials: A
authors.lastname: Gersappe
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Carson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Weber
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Register
authors.forename: Yong Q
authors.initials: YQ
authors.lastname: Chen
authors.forename: Raymond B
authors.initials: RB
authors.lastname: Penn
authors.forename: George
authors.initials: G
authors.lastname: Kulik
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008954:Models, Biological; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D051025:bcl-Associated Death Protein / Q000378:metabolism*
chemical_list: D000322:Adrenergic Agonists; D051025:bcl-Associated Death Protein; D017868:Cyclic AMP-Dependent Protein Kinases; D004837:Epinephrine