Chemopreventive effects of pterostilbene through p53 and cell cycle in mouse lung of squamous cell carcinoma model

Sci Rep. 2021 Jul 21;11(1):14862. doi: 10.1038/s41598-021-94508-7.

Abstract

Cell proliferation and cell death abnormalities are strongly linked to the development of cancer, including lung cancer. The purpose of this study was to investigate the effect of pterostilbene on cell proliferation and cell death via cell cycle arrest during the transition from G1 to S phase and the p53 pathway. A total of 24 female Balb/C mice were randomly categorized into four groups (n = 6): N-nitroso-tris-chloroethyl urea (NTCU) induced SCC of the lungs, vehicle control, low dose of 10 mg/kg PS + NTCU (PS10), and high dose of 50 mg/kg PS + NTCU (PS50). At week 26, all lungs were harvested for immunohistochemistry and Western blotting analysis. Ki-67 expression is significantly lower, while caspase-3 expression is significantly higher in PS10 and PS50 as compared to the NTCU (p < 0.05). There was a significant decrease in cyclin D1 and cyclin E2 protein expression in PS10 and PS50 when compared to the NTCU (p < 0.05). PS50 significantly increased p53, p21, and p27 protein expression when compared to NTCU (p < 0.05). Pterostilbene is a potential chemoprevention agent for lung SCC as it has the ability to upregulate the p53/p21 pathway, causing cell cycle arrest.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticarcinogenic Agents*
  • Apoptosis / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology*
  • Cell Cycle Checkpoints / drug effects*
  • Cell Cycle Checkpoints / genetics*
  • Cell Proliferation / genetics
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Cyclins / genetics
  • Cyclins / metabolism
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Female
  • G1 Phase Cell Cycle Checkpoints / drug effects*
  • G1 Phase Cell Cycle Checkpoints / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Stilbenes / pharmacology*
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism*
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • Anticarcinogenic Agents
  • Ccnd1 protein, mouse
  • Ccne2 protein, mouse
  • Cyclins
  • Stilbenes
  • Trp53 protein, mouse
  • Tumor Suppressor Protein p53
  • Cyclin D1
  • pterostilbene