title: MK615 decreases RAGE expression and inhibits TAGE-induced proliferation in hepatocellular carcinoma cells.
abstract: OBJECTIVE
  To investigate the proliferative effect of advanced glycation end-products (AGEs) and the role of their cellular receptor (RAGE) on hepatocellular carcinoma (HCC) cells, and the inhibitory effects of MK615, an extract from Japanese apricot, against AGEs were also evaluated.
  
  
  METHODS
  Two HCC cell lines, HuH7 and HepG2, were used. Expression of RAGE was investigated by polymerase chain reaction, Western blotting, and flow cytometry (FACS). The effect of MK615 on RAGE expression was also evaluated by FACS. The proliferative effects of a control (unglycated bovine serum albumin), glucose-derived AGEs (Glc-AGE), and glyceraldehyde-derived AGEs (Glycer-AGE), and the anti-proliferative effect of MK615 against AGEs, were evaluated using MTT assays.
  
  
  RESULTS
  Expression of RAGE was confirmed at both the mRNA and protein levels in both HuH7 and HepG2. FACS revealed that the level of RAGE expression was higher in HuH7 than in HepG2. Treatment with 0.1 μg/mL MK615 decreased the expression level of RAGE from 24.3% to 3.7% in HuH7 and from 6.2% to 4.8% in HepG2. The growth indices for the control, Glc-AGE, and Glycer-AGE were 1.06 ± 0.08, 0.99 ± 0.04, and 1.38 ± 0.05, respectively, in HuH7 (P = 0.037), and were 1.03 ± 0.04, 1.04 ± 0.03, and 1.07 ± 0.05, respectively, in HepG2 (P > 0.05). When the cells were cultured simultaneously with Glycer-AGE and MK615, MK615 abrogated the proliferative effect of Glycer-AGE in HuH7.
  
  
  CONCLUSIONS
  Only Glycer-AGE has a proliferative effect on HuH7, which expresses a higher level of RAGE. MK615 suppresses the proliferative effect of Glycer-AGE on HuH7 by decreasing the expression of RAGE.
authors.affiliation: Second Department of Surgery, Dokkyo Medical University, School of Medicine, Kitakobayashi 880, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Sakuraoka
authors.forename: Tokihiko
authors.initials: T
authors.lastname: Sawada
authors.forename: Toshie
authors.initials: T
authors.lastname: Okada
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shiraki
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Miura
authors.forename: Katsuya
authors.initials: K
authors.lastname: Hiraishi
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Ohsawa
authors.forename: Masakazu
authors.initials: M
authors.lastname: Adachi
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Takino
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kubota
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D017127:Glycation End Products, Advanced / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000473:pathology*; D010936:Plant Extracts / Q000494:pharmacology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D017127:Glycation End Products, Advanced; D007093:Imidazoles; C517469:MK615 extract; D010936:Plant Extracts; D020033:Protein Isoforms; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C533873:TAGE compound