Resveratrol inhibits the expression of RYR2 and is a potential treatment for pancreatic cancer

Naunyn Schmiedebergs Arch Pharmacol. 2022 Mar;395(3):315-324. doi: 10.1007/s00210-022-02203-9. Epub 2022 Jan 19.

Abstract

Resveratrol is a polyphonous natural compound that has cardioprotective, anticancer, and anti-inflammatory properties. Studies have proved that resveratrol (RES) inhibits cancer cell proliferation, migration, and invasion and promotes apoptosis. Elevated expression of ryanodine receptor type 2 (RYR2) may participate in the pathway responsible for calcium metabolism as well as anti-apoptosis and anti-autophagy events in malignant tumor cells. However, the underlying molecular mechanisms of RES anticancer effects with RYR2 are not completely understood in pancreatic cancer. The aim of the present study was tantamount to study the effect of RES in human pancreatic cancer and investigate the underlying mechanisms of RES. We found that RES inhibits proliferation, migration, and invasion and suppresses RYR2 expression in pancreatic cancer cells. In addition, RYR2 knockdown impedes the proliferation, migration, and invasiveness of pancreatic cancer cells. RYR2 knockdown can also increase PTEN expression, while increased RYR2 expression can inhibit PTEN expression. Moreover, RES can upregulate PTEN expression. Taken together, these results indicate that RES could play an antitumor role by decreasing RYR2 expression.

Keywords: Invasion; Migration; Pancreatic cancer; RYR2; Resveratrol.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Gene Knockdown Techniques
  • Humans
  • Neoplasm Invasiveness / prevention & control
  • PTEN Phosphohydrolase / genetics
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology
  • Resveratrol / pharmacology*
  • Ryanodine Receptor Calcium Release Channel / genetics*

Substances

  • Antineoplastic Agents, Phytogenic
  • RyR2 protein, human
  • Ryanodine Receptor Calcium Release Channel
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Resveratrol