Prevention of pancreatic cancer by the beta-blocker propranolol
Al-Wadei H et al. - In a trial to examine whether propranolol prevents development of pancreatic ductal adenocarcinoma (PDAC) induced in hamsters with ethanol-induced pancreatitis by nicotine-derived nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), it appears that increased cAMP signaling is an important factor that drives development and progression of PDAC and that inhibition of cAMP formation is a promising new target for prevention and adjuvant therapy of PDAC. Methods- This study investigates whether propranolol prevents development of PDAC induced in hamsters with ethanol-induced pancreatitis by NNK.
Results- Propranolol had strong cancer preventive effects in this animal model.
- Western blots of pancreatic duct cells and PDAC cells harvested by laser capture microscopy showed significant upregulation of the α7 nAChR associated with significant inductions of p-CREB, p-ERK1/2, and increases in epidermal growth factor and vascular endothelial growth factor in PDAC cells of hamsters not treated with propranolol.
- These effects were reversed by treatment with propranolol.
- These data suggest that propranolol may prevent development of PDAC by blocking cAMP-dependent intracellular signaling, cAMP-dependent release of epidermal growth factor, and PKA-dependent release of vascular endothelial growth factor, while additionally downregulating the α7 nAChR by inhibiting cAMP-mediated subunit assembly.
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