Downregulation of MDM2 by small interference RNA induces apoptosis and sensitizes MCF-7 breast cells to resveratrol

Chem Biol Drug Des. 2023 May;101(5):1082-1088. doi: 10.1111/cbdd.14190. Epub 2022 Dec 28.

Abstract

Recent studies have demonstrated the mouse double minute gene (MDM2), a main oncogene, as a novel and interesting therapeutic target for cancer therapy. The aim of this study was to investigate the involvement of MDM2 in antiproliferative and antimetastatic effects of resveratrol in breast cancer cells. MCF-7 cells were transfected with siRNA against MDM2 and resveratrol. Proliferation and apoptosis were evaluated by MTT assay and cell death ELISA assay, respectively. MDM2, p53, Bax, Bcl-2, caspase-3, MMP-2, and MMP9 expressions were determined by qRT-PCR and Western blotting. Transfection with si-MDM2 significantly suppressed the expression of MDM2 expression, resulting in MCF-7 cell growth inhibition and spontaneous apoptosis. Pretreatment with Si-MDM2 synergically increased antiproliferation and antimetatstatic effects of resveratrol. No significant anticancer effects were detected with negative control siRNA treatment. Our findings suggest that silencing of MDM2 by specific siRNA effectively induce apoptosis and also enhanced anticancer effects of resveratrol. Therefore, siMDM2 may be a potent combination in breast therapy.

Keywords: MDM2; breast cancer; polyphenols; resveratrol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Breast Neoplasms* / drug therapy
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation
  • Female
  • Humans
  • MCF-7 Cells
  • Mice
  • Proto-Oncogene Proteins c-mdm2 / genetics
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Resveratrol / pharmacology

Substances

  • Resveratrol
  • RNA, Small Interfering
  • Proto-Oncogene Proteins c-mdm2
  • MDM2 protein, human