ono-di-004 and epigallocatechin-gallate

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.

Topics: Alprostadil; Apoptosis; Carcinoma, Hepatocellular; Catechin; Cell Movement; Cell Proliferation; Dinoprostone; Drug Synergism; Hep G2 Cells; Humans; Liver Neoplasms; Receptors, Prostaglandin E, EP1 Subtype; Wound Healing

To investigate the effects of (-)-epigallocatechin-3-gallate (EGCG), an active compound in green tea, on prostaglandin E(2) (PGE(2))-induced proliferation and migration, and the expression of prostanoid EP(1) receptors in hepatocellular carcinoma (HCC) cells.. HCC cell line HepG2, human hepatoma cell lines MHCC-97L, MHCC-97H and human hepatocyte cell line L02 were used. Cell viability was analyzed using MTT assay. PGE(2) production was determined with immunoassay. Wound healing assay and transwell filter assay were employed to assess the extent of HCC cell migration. The expression of EP(1) receptor and Gq protein were examined using Western blot assay.. PGE(2) (4-40000 nmol/L) or the EP(1) receptor agonist ONO-DI-004 (400-4000 nmol/L) increased the viability and migration of HepG2 cells in concentration-dependent manners. EGCG (100 μg/mL) significantly inhibited the viability and migration of HepG2 cells induced by PGE(2) or ONO-DI-004. HepG2 cells secreted an abundant amount of PGE(2) into the medium, and EGCG (100 μg/mL) significantly inhibited the PGE(2)production and EP(1) receptor expression in HepG2 cells. EGCG (100 μg/mL) also inhibited the viability of MHCC-97L cells, but not that of MHCC-97H cells. Both EGCG (100 μg/mL) and EP(1) receptor antagonist ONO-8711 inhibited PGE(2) 4 μmol/L and ONO-DI-004 400 nmol/L-induced growth and migration of HepG2 cells. Both EGCG (100 μg/mL) and ONO-8711 210 nmol/L inhibited PGE(2)- and ONO-DI-004-induced EP(1) expression. EGCG and ONO-8711 had synergistic effects in inhibiting EP(1) receptor expression. PGE(2), ONO-DI-004, ONO-8711, and EGCG had no effects on Gq expression in HepG2 cells, respectively.. These findings suggest that the anti-HCC effects of EGCG might be mediated, at least partially, through the suppressing EP(1) receptor expression and PGE(2) production.

Topics: Alprostadil; Antineoplastic Agents, Phytogenic; Blotting, Western; Bridged Bicyclo Compounds; Caproates; Carcinoma, Hepatocellular; Catechin; Cell Movement; Cell Proliferation; Cell Survival; Dinoprostone; Dose-Response Relationship, Drug; GTP-Binding Protein alpha Subunits, Gq-G11; Hep G2 Cells; Humans; Immunoassay; Liver Neoplasms; Neoplasm Invasiveness; Receptors, Prostaglandin E, EP1 Subtype; Time Factors