Piceatannol induces apoptotic cell death through activation of caspase-dependent pathway and upregulation of ROS-mediated mitochondrial dysfunction in pancreatic cancer cells

Mol Biol Rep. 2022 Dec;49(12):11947-11957. doi: 10.1007/s11033-022-08006-8. Epub 2022 Oct 19.

Abstract

Background: Piceatannol is a naturally occurring plant-derived phenolic compound (stilbenoid), an analogue of resveratrol. It has been shown that, piceatannol has biological activity properties such as antiproliferative, antioxidative, anti-inflammatory and proapoptotic, in various human cancer studies in vitro and in vivo.

Objectives and methods: In this study, it was aimed to investigate whether piceatannol induces apoptosis through anticancer activity methods (cell viability, colony formation, annexin-V/7-AAD, ROS (Reactive oxygen species), MMP (Mitochondrial membrane potential), wound healing, invasion assay, RT-qPCR (Real-Time Quantitative Polymerase Chain Reaction), western blotting in PANC-1 and MIA PaCa-2 pancreatic cancer (PC) cell lines.

Results: According to our results, piceatannol decreased cell viability in a dose and time-dependent manner [the half-maximal inhibitory concentration (IC50): 60 µM in PANC-1 and IC50: 90 µM in MIA PaCa-2 cell line at 48 h (h)] and caused significant changes in the expression of apoptosis-related genes and protein. Piceatannol induced apoptosis in PANC-1 and MIA PaCa-2 cells, accompanied by increased ROS production, decreased MMP, and increased Caspase-3-9 activity. Piceatannol also inhibited colony-forming abilities, invasion, and migration of PC cells.

Conclusion: Our results show that piceatannol has an anti-cancerogenic effect on PANC-1 and MIA PaCa-2 cells, and exerts this effect by suppressing proliferation and inducing apoptosis. Therefore, piceatannol could be considered to be a potential chemotherapeutic agent candidate for the treatment and prevention of PC.

Keywords: Anticancer agents; Apoptosis; Pancreatic cancer cells; Phenolic compound; Piceatannol; Resveratrol-analogue.

MeSH terms

  • Apoptosis
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Survival
  • Humans
  • Mitochondria / metabolism
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / metabolism
  • Reactive Oxygen Species / metabolism
  • Stilbenes* / pharmacology
  • Up-Regulation

Substances

  • Caspases
  • 3,3',4,5'-tetrahydroxystilbene
  • Reactive Oxygen Species
  • Stilbenes