Degradation of EGF activated mitogenic signaling cascade by 3,4-dihydroxyphenyl acetic acid and (+)-epoxydon from marine algae in HeLa cells

Abstract

Epidermal Growth Factor Receptor (EGFR) is a member of the Receptor Tyrosine Kinase (RTK) protein family. EGFR exists on the cell surface and is activated by binding of its specific ligands. The ligand such as epidermal growth factor leads to receptor heterodimerization and stimulates intrinsic intracellular protein-tyrosine kinase activity. As a result, autophosphorylation of several tyrosine residues in the C-terminal domain of EGFR occurs. These activations by EGFR phosphorylation are worth studying for cancer therapy because EGFR regulates many cellular processes including cell proliferation, differentiation and cell survival. Hence, the down regulation of EGFR results in inhibition of signaling cascades amenable for cell cycle progression. Here, we described the effects of several compounds in human cervical HeLa cancer cells. The two compounds from marine algae suppressed EGFR activity in vitro and reduced the viable numbers of HeLa cells in a dose-dependent manner. Immunoblotting analysis revealed that both compounds induced inhibition of cell growth such as low expression of mitogenic signaling cascade, inactivation of p90RSK and release of cytochrome c from mitochondria. It suggested that decreased expression level of active EGFR and EGF-related downstream molecules by treatment of the compounds may be involved in the inhibition of cell growth and inducement for apoptosis.