Synergetic Effect of EP1 Receptor Antagonist and (-)-Epigallocatechin-3-gallate in Hepatocellular Carcinoma

Pharmacology. 2019;104(5-6):267-275. doi: 10.1159/000502076. Epub 2019 Aug 21.

Abstract

Epigallocatechin-3-gallate (EGCG), the principal catechin of green tea, modulates different molecular mechanisms underlying hepatocellular carcinoma (HCC). Accumulating studies showed that the activation of prostaglandin (PG) receptor EP1 promotes cell migration and invasion in different cancers, which could be inverted by blocking the EP1 receptor. This study investigated the synergetic effects of EP1-selective antagonist ONO-8711 and EGCG treatment on HCC to better understand the potential strategy to treat HCC. We found that EGCG significantly inhibited PGE2 and EP1-selective agonist induced migration of HCC cells and increased the ratio of Bax/Bcl-2 even in the presence of ONO-DI-004 or PGE2. ONO-8711 significantly inhibited PGE2-induced HCC proliferation while increased the inhibitory effect of EGCG on HCC cell viability and migration ability compared with EGCG alone. These findings suggest that a combination of ONO-8711 and EGCG is a potential treatment for HCC therapy.

Keywords: Epigallocatechin-3-gallate; Hepatocellular carcinoma; Selective EP1 receptor antagonist.

MeSH terms

  • Alprostadil / analogs & derivatives*
  • Alprostadil / pharmacology
  • Apoptosis / drug effects
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Dinoprostone / metabolism
  • Drug Synergism
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Receptors, Prostaglandin E, EP1 Subtype / antagonists & inhibitors*
  • Receptors, Prostaglandin E, EP1 Subtype / metabolism
  • Wound Healing / drug effects

Substances

  • ONO-DI-004
  • Receptors, Prostaglandin E, EP1 Subtype
  • Catechin
  • epigallocatechin gallate
  • Alprostadil
  • Dinoprostone