Carcinogenesis, Vol. 23, No. 7, 1163-1169,
July 2002
© 2002 Oxford University Press
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION |
The roles of ERK1/2 and p38 MAP kinases in the preventive mechanisms of mushroom Phellinus linteus against the inhibition of gap junctional intercellular communication by hydrogen peroxide
1 Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul National University, Suwon 441-744, South Korea,
2 Graduate School of East-West Medical Science, Kyunghee University, Suwon, South Korea and
3 Iljo Biological Industrial Company Limited, South Korea
Modulation of gap junctional intercellular communication (GJIC) is a known cellular event associated with tumor promotion. The present study was undertaken to test the potential preventive effect of mushroom Phellinus linteus extract (PL) on the inhibition of GJIC, induced by hydrogen peroxide (H2O2), in WB-F344 rat liver epithelial cells (WB cells). Cells were pre-incubated with PL (5 and 25 µg/ml) for 24 h and this was followed by co-treatment with PL and H2O2 (500 µM) for 1 h. PL (at 5 and 25 µg/ml) prevented the inhibition of GJIC and blocked the hyper-phosphorylation of connexin 43 by H2O2. Moreover, H2O2 activated p38 kinase, extracellular signal-regulated protein kinases (ERK)1/2 and c-Jun N-terminal kinase (JNK) in WB cells. The present study indicates that PL is able to inactivate both ERK1/2 and p38 MAP kinases. However, PL did not affect the JNK pathway. For this reason, to elucidate the relation between MAP kinases and GJIC, we treated cells with PD98059 (an MEK inhibitor) and SB202190 (a p38 kinase inhibitor). These inhibitors were also found to prevent the inhibition of GJIC induced by H2O2, which suggests that PL may act as a natural anticancer product by preventing the inhibition of GJIC through the inactivation of ERK1/2 and p38 MAP kinases. In addition, our results indicate that the p38 kinase signaling pathway may be closely related functionally to the gap junction in rat liver epithelial cells.
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