Inhibition of pancreatic cancer cell proliferation by propranolol occurs through apoptosis induction: The study of β-adrenoceptor antagonist's anticancer effect in pancreatic cancer cell

Objectives:: Propranolol inhibited pancreatic cancer cell proliferation by blocking signaling through the β-adrenoceptor. We hypothesized that propranolol may suppress pancreatic cancer cell growth through induction of apoptosis. Methods:: The β-adrenoceptor antagonist propranolol, β1-adrenoceptor antagonist metoprolol, and β2-adrenoceptor antagonist butoxamine were used to induce apoptosis in PC-2 cells. The mRNA and protein expression of β1- and β2-adrenoceptors was analyzed using reverse transcriptase-polymerase chain reaction and Western blot. The apoptotic index was determined using Hoechst 33342 fluorescent staining, TUNEL, and annexin V and fluorescein isothiocyanate/propidium iodide flow cytometry assay. The expression of caspase 3, caspase 9, and caspase 8 was analyzed using Western blotting. Results:: PC-2 cell line expressed mRNA and protein for both of β1- and β2-adrenoceptors. The Hoechst staining, TUNEL, and flow cytometry assay documented that the 3 drugs increased the number of apoptotic cells; the rate of apoptosis was the highest using butoxamine followed by propranolol, whereas the least was using metoprolol. β-Adrenoceptor antagonists therapy affected caspase 3 and caspase 9 expression. Conclusions:: The rate of apoptosis in PC-2 cells was higher after treatment with butoxamine than propranolol, suggesting that propranolol induces apoptosis in PC-2 cells via the β2-adrenoceptors principally. Our data could be useful for developing β-adrenoceptor antagonists for inducing apoptosis in pancreatic cancer cells.