Epigallocatechin gallate (EGCG) suppresses growth and tumorigenicity in breast cancer cells by downregulation of miR-25

Bioengineered. 2019 Dec;10(1):374-382. doi: 10.1080/21655979.2019.1657327.

Abstract

The aim of the present study was to investigate the anticancer effects and potential mechanisms of polyphenol epigallocatechin-3-gallate (EGCG) on breast cancer MCF-7 cells in vitro and in vivo. Our results showed that EGCG significantly inhibited MCF-7 cell viability in a time- and dose-dependent manner. Flow cytometry analysis indicated that EGCG induced apoptosis and disrupted cell cycle progression at G2/M phase. Moreover, EGCG inhibited miR-25 expression and increased PARP, pro-caspase-3 and pro-caspase-9 at protein levels. Restoration of miR-25 inhibited EGCG-induced cell apoptosis. Furthermore, EGCG suppressed tumor growth in vivo by downregulating the expression of miR-25 and proteins associated with apoptosis, which was further confirmed by a reduction of Ki-67 and increase of pro-apoptotic PARP expression as determined by immunohistochemistry staining. These findings indicate that EGCG possesses chemopreventive potential in breast cancer which may serve as a promising anticancer agent for clinical applications.

Keywords: Polyphenol epigallocatechin-3-gallate; apoptosis; breast cancer; proliferation.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 9 / genetics
  • Caspase 9 / metabolism
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • G2 Phase Cell Cycle Checkpoints / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • MCF-7 Cells
  • Mice
  • Mice, SCID
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism
  • Signal Transduction
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Ki-67 Antigen
  • MIRN25 microRNA, human
  • MicroRNAs
  • Catechin
  • epigallocatechin gallate
  • Poly(ADP-ribose) Polymerases
  • Caspase 3
  • Caspase 9