Inhibition of Pancreatic Cancer Cell Proliferation by Propranolol Occurs Through Apoptosis Induction

OBJECTIVES: Propranolol inhibited pancreatic cancer cell proliferation by blocking signaling through the beta-adrenoceptor. We hypothesized that propranolol may suppress pancreatic cancer cell growth through induction of apoptosis. METHODS: The beta-adrenoceptor antagonist propranolol, beta1-adrenoceptor antagonist metoprolol, and beta2-adrenoceptor antagonist butoxamine were used to induce apoptosis in PC-2 cells. The mRNA and protein expression of beta1- and beta2-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 beta1- and beta2-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. beta-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 beta2-adrenoceptors principally. Our data could be useful for developing beta-adrenoceptor antagonists for inducing apoptosis in pancreatic cancer cells.