title: 3,4-dihydroxyphenyl acetic acid and (+)-epoxydon isolated from marine algae-derived microorganisms induce down regulation of epidermal growth factor activated mitogenic signaling cascade in Hela cells.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine kinase (RTK) family. Epidermal growth factor induces its dimerization and stimulates phosphorylation of intracellular tyrosine residues. Phosphorylation of EGFR is studied for cancer therapy because EGFR regulates many cellular processes including cell proliferation, differentiation, and survival. Hence, down-regulation of EGFR kinase activity results in inhibition of signaling cascades amenable for proliferation and progression of cell cycle.
  
  
  METHODS
  In the study, we purified 3,4-dihydroxyphenyl acetic acid and (+)-epoxydon from Aspergillus sp. isolated from marine brown alga Ishige okamurae and Phoma herbarum isolated from marine red alga Hypnea saidana respectively and determined its anti-tumor activities against HeLa human cervical cancer cells.
  
  
  RESULTS
  Two compounds suppressed EGFR activity in vitro with IC50 values for 3,4-dihydroxyphenyl acetic acid and (+)-epoxydon were 2.8 and 0.6 μg/mL respectively and reduced the viable numbers of HeLa cells. Immunoblotting analysis exhibited that the compounds induced inhibition of cell growth by causing downregulation of the mitogenic signaling cascade, inactivation of p90RSK, and release of cytochrome c from mitochondria.
  
  
  CONCLUSIONS
  Results suggest that decreased expression of active EGFR and EGFR-related downstream molecules by treatment with the compounds may results in the inhibition of cell growth and inducement of apoptosis.
authors.affiliation: Department of Microbiology College of Natural Sciences, Pukyong National University, Busan 608-737, Korea.
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Jo
authors.affiliation: Department of Microbiology College of Natural Sciences, Pukyong National University, Busan 608-737, Korea.
authors.forename: Seong Ja
authors.initials: SJ
authors.lastname: Bae
authors.affiliation: Department of Chemistry College of Natural Sciences, Pukyong National University, Busan 608-737, Korea.
authors.forename: Byeng Wha
authors.initials: BW
authors.lastname: Son
authors.affiliation: Department of Dermatology School of Medicine, Gyeongsang National University & Hospital, Jinju 660-701, Korea.
authors.forename: Chi Yeon
authors.initials: CY
authors.lastname: Kim
authors.affiliation: Department of Microbiology College of Natural Sciences, Pukyong National University, Busan 608-737, Korea.
authors.forename: Gun Do
authors.initials: GD
authors.lastname: Kim