Epinephrine protects cancer cells from apoptosis via activation of cAMP-dependent protein kinase and BAD phosphorylation.
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.
Sastry
Konduru S R
KS
Department of Cancer Biology, Section on Comparative Medicine, and Center for Human Genomics, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA.
Karpova
Yelena
Y
Prokopovich
Sergey
S
Smith
Adrienne J
AJ
Essau
Brian
B
Gersappe
Avynash
A
Carson
Jonathan P
JP
Weber
Michael J
MJ
Register
Thomas C
TC
Chen
Yong Q
YQ
Penn
Raymond B
RB
Kulik
George
G
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*
D000322:Adrenergic Agonists; D051025:bcl-Associated Death Protein; D017868:Cyclic AMP-Dependent Protein Kinases; D004837:Epinephrine