Cross-talk of cholinergic and beta-adrenergic receptor signalling in chronic myeloid leukemia K562 cells

In many studies on breast, skin and intestinal cancers, beta-adrenergic receptor antagonists have been shown to inhibit cell proliferation and angiogenesis and increase apoptosis in cancers. Carbachol inhibits chronic myeloid leukaemia K562 cell proliferation. Beta-blockers are known to inhibit cell progression. The aim of this study is to explain the mechanism of action of beta-adrenergic receptors agonists and antagonists on apoptosis in chronic myeloid leukaemia cells. We tried to determine the effect of combined treatment of beta-adrenergic and cholinergic drugs on adrenergic beta(1) and beta(2) gene expression, cell proliferation and apoptosis in chronic myeloid leukaemia K562 cells. Cell proliferation was evaluated by the 5-bromo-2-deoxy-uridine (BrdU) incorporation kit. Caspase 3, 8, 9 activities were measured by the caspase assay kit. Protein expression level was detected by western blotting. We found that exposure to propranolol either by combination with carbachol facilitates additive effects on inhibition of caspase 3 and 8 expression in chronic myeloid leukaemia K562 cells. However, caspase 9 expression level was increased by propranolol alone or with propranolol and carbachol combination. The combined therapy of cholinergic and adrenergic receptor drugs will decrease cell proliferation in K562 cells. This decrease in cell proliferation may be mediated by the mitochondrial-dependent intrinsic apoptosis pathway.

Automated summary

In this study, the mechanism of action of beta-adrenergic receptors agonists and antagonists on apoptosis in chronic myeloid leukaemia cells was investigated. The combined treatment of beta-adrenergic and cholinergic drugs was found to decrease cell proliferation in K562 cells by inducing the mitochondrial-dependent intrinsic apoptosis pathway.