Brief Article
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World J Gastroenterol. Nov 14, 2010; 16(42): 5334-5341
Published online Nov 14, 2010. doi: 10.3748/wjg.v16.i42.5334
MK615 decreases RAGE expression and inhibits TAGE-induced proliferation in hepatocellular carcinoma cells
Yuhki Sakuraoka, Tokihiko Sawada, Toshie Okada, Takayuki Shiraki, Yoshikazu Miura, Katsuya Hiraishi, Tatsushi Ohsawa, Masakazu Adachi, Jun-ichi Takino, Masayoshi Takeuchi, Keiichi Kubota
Yuhki Sakuraoka, Tokihiko Sawada, Toshie Okada, Takayuki Shiraki, Keiichi Kubota, Second Department of Surgery, Dokkyo Medical University, School of Medicine, Kitakobayashi 880, Mibu, Shimotsuga, Tochigi 321-0293, Japan
Yoshikazu Miura, Public Health, Dokkyo Medical University, School of Medicine, Kitakobayashi 880, Mibu, Shimotsuga, Tochigi 321-0293, Japan
Katsuya Hiraishi, Tatsushi Ohsawa, Masakazu Adachi, AdaBio, Co. Ltd., 21-1 Kenzaki-machi, Takasaki, Gunma 370-0883, Japan
Jun-ichi Takino, Masayoshi Takeuchi, Department of Life Pharmacy, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3, Kanagawa-machi, Kanazawa, Ishikawa 920-1181, Japan
Author contributions: Sakuraoka Y and Sawada T performed the study and wrote the paper; Okada T and Shiraki T assisted with the study; Sawada T designed the study; Miura Y and Kubota K assisted in the study and reviewed the paper; Hiraishi K, Ohsawa T, Adachi M, Takino J and Takeuchi M contributed experimental reagents.
Supported by A Research Grant from the Biomarker Society
Correspondence to: Tokihiko Sawada, MD, PhD, Second Department of Surgery, Dokkyo Medical University, School of Medicine, Kitakobayashi 880, Mibu, Shimotsuga, Tochigi 321-0293, Japan. tsawada@dokkyomed.ac.jp
Telephone: +81-282-861111 Fax: +81-282-866317
Received: May 31, 2010
Revised: June 7, 2010
Accepted: June 14, 2010
Published online: November 14, 2010
Abstract

AIM: 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 cytemetry (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.

CONCLUSION: 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.

Keywords: Hepatocellular carcinoma, Receptor of advanced glycation end-product, Advanced glycation end-products, MK615, Toxic advanced glycation end-products