Inhibition of pancreatic cancer cell proliferation by propranolol occurs through apoptosis induction: the study of beta-adrenoceptor antagonist's anticancer effect in pancreatic cancer cell.
OBJECTIVE
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.
Zhang
Dong
D
Department of Hepatobiliary and Pancreas Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
Ma
Qingyong
Q
Shen
Sugang
S
Hu
Hengtong
H
D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D017304:Annexin A5 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002078:Butoxamine / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008790:Metoprolol / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011433:Propranolol / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism
D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D017304:Annexin A5; D000970:Antineoplastic Agents; D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D002078:Butoxamine; D011433:Propranolol; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D008790:Metoprolol