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

Pancreas. 2009 Jan;38(1):94-100. doi: 10.1097/MPA.0b013e318184f50c.


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.

MeSH terms

  • Adrenergic beta-1 Receptor Antagonists*
  • Adrenergic beta-2 Receptor Antagonists*
  • Adrenergic beta-Antagonists / pharmacology*
  • Annexin A5 / metabolism
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Butoxamine / pharmacology
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Metoprolol / pharmacology
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Propranolol / pharmacology*
  • RNA, Messenger / metabolism
  • Receptors, Adrenergic, beta-1 / genetics
  • Receptors, Adrenergic, beta-1 / metabolism
  • Receptors, Adrenergic, beta-2 / genetics
  • Receptors, Adrenergic, beta-2 / metabolism


  • Adrenergic beta-1 Receptor Antagonists
  • Adrenergic beta-2 Receptor Antagonists
  • Adrenergic beta-Antagonists
  • Annexin A5
  • Antineoplastic Agents
  • RNA, Messenger
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2
  • Butoxamine
  • Propranolol
  • CASP3 protein, human
  • CASP8 protein, human
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Metoprolol