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Issue title: Free Radicals in Biology and Medicine: From Inflammation to Biotechnology
Article type: Research Article
Authors: Park, Jung-Ran | Park, Joon-Suk | Jo, Eun-Hye | Hwang, Jae-Woong | Kim, Sun-Jung | Ra, Jeong-Chan | Aruoma, Okezie I. | Lee, Yong-Soon | Kang, Kyung-Sun
Affiliations: Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine and BK 21 Program for Veterinary Science, Seoul National University, Seoul 151-742, South Korea | Faculty of Health and Social Care, London South Bank University, 103 Borough Road, London, SE1 0AA, UK | RNL BIO, Co., Ltd., Central Research Institute, 2F, Sungmoon B/D, 1-26, Yangjae-dong, Seocho-gu, Seoul 137-886, South Korea
Note: [] Address for correspondence: Professor Kyung-Sun Kang, Ph. D., DVM, Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, Sillim 9-dong, Gwanak-gu, Seoul 151-742, South Korea. Tel.: +82 2 880 1246; Fax: +82 2 876 7610; E-mail: kangpub@snu.ac.kr
Abstract: Chaga mushroom (Inonotus obliquus) has continued to receive attention as a folk medicine with indications for the treatment of cancers and digestive diseases. The anticarcinogenic effect of Chaga mushroom extract was investigated using a model system of gap junctional intercellular communication (GJIC) in WB-F344 normal rat liver epithelial cells. The cells were pre-incubated with Chaga mushroom extracts (5, 10, 20 μg/ml) for 24 h and this was followed by co-treatment with Chaga mushroom extracts and TPA (12-O-tetradecanoylphorbol-13-acetate, 10 ng/ml) for 1 h. The inhibition of GJIC by TPA (12-O-tetradecanoylphorbol-13-acetate), promoter of cancer, was prevented with treatment of Chaga mushroom extracts. Similarly, the increased phosphorylated ERK1/2 and p38 protein kinases were markedly reduced in Chaga mushroom extracts-treated cells. There was no change in the JNK kinase protein level, suggesting that Chaga mushroom extracts could only block the activation of ERK1/2 and p38 MAP kinase. The Chaga mushroom extracts further prevented the inhibition of GJIC through the blocking of Cx43 phosphorylation. Indeed cell-to-cell communication through gap junctional channels is a critical factor in the life and death balance of cells because GJIC has an important function in maintaining tissue homeostasis through the regulation of cell growth, differentiation, apoptosis and adaptive functions of differentiated cells. Thus Chaga mushroom may act as a natural anticancer product by preventing the inhibition of GJIC through the inactivation of ERK1/2 and p38 MAP kinase.
Keywords: Inonotus obliquus (Chaga mushroom), gap junctional intercellular communication, connexin 43, ERK 1/2, p38 MAP kinase, chemoprevention and signaling mechanisms
Journal: BioFactors, vol. 27, no. 1-4, pp. 147-155, 2006
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