8‑Gingerol regulates colorectal cancer cell proliferation and migration through the EGFR/STAT/ERK pathway

Int J Oncol. 2020 Jan;56(1):390-397. doi: 10.3892/ijo.2019.4934. Epub 2019 Dec 3.

Abstract

8‑Gingerol, which is extracted from ginger (Zingiber officinale Roscoe), has been shown to possess antioxidant and anti‑inflammatory properties. However, the antitumor effect of 8‑gingerol has not been fully elucidated. The aim of the present study was to investigate the therapeutic potential of 8‑gingerol against colorectal cancer (CRC). The results demonstrated that 8‑gingerol significantly inhibited cell proliferation in CRC cell models. Treatment of CRC cells with 8‑gingerol resulted in dose‑dependent decreases in migration and invasion. The inhibitory effect of 8‑gingerol on CRC cell growth was attributed to cell cycle arrest and increased apoptosis. Moreover, to the best of our knowledge, the present study was the first to demonstrate that 8‑gingerol acted as an inhibitor of epidermal growth factor receptor (EGFR) signaling. 8‑Gingerol inhibited CRC cell proliferation and migration by targeting the EGFR/signal transducer and activator of transcription/extracellular signal‑regulated kinase pathway, and the effects of 8‑gingerol depended on the expression of EGFR. Moreover, 8‑gingerol reduced the effective dosage of 5‑fluorouracil and, thereby, the toxicity of drug combination therapy. These data suggest that 8‑gingerol may be a promising candidate for the development of novel anticancer agents against CRC.

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Catechols / pharmacology*
  • Cell Cycle
  • Cell Movement*
  • Cell Proliferation*
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Fatty Alcohols / pharmacology*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • Catechols
  • Fatty Alcohols
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • EGFR protein, human
  • ErbB Receptors
  • MAPK1 protein, human
  • MAPK3 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • 8-gingerol