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P27Kip1 up‐regulation via skp2 down‐regulation by an ethanol extract of Rhus verniciflua Stokes induced cell cycle arrest in AGS gastric cancer cells
Author(s) -
Kim Ji Hye,
Jun ChanYong,
Park JongHyeong,
Jung WooSang,
Moon SangKwan,
Yim HeeSun,
Ko SeongGyu
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb49
Subject(s) - apoptosis , cell cycle , cell cycle checkpoint , cancer cell , kinase , cell growth , cancer , chemistry , pharmacology , cancer research , biochemistry , biology , genetics
Botanical preparations are widely used by patient with cancer in Korea, Japan and China. Rhus verniciflua Stokes (RVS) has traditionally been used as a medicinal ingredient for the therapy of stomach and uterine cancer. In this study, we showed that an ethanol extract of RVS induced G1 cell cycle arrest by regulation of p27Kip1 accumulation against human gastric cancer cell lines. AGS (gastric cancer cells) and RIE1 (rat intestinal epithelial cells) were treated to 10 – 100 ug/ml of an ethanol extract of RVS. Exposure to RVS extract (50 ug/ml) resulted in a synergistic inhibitory effect on cell growth in AGS cells. The extract induced G1‐cell cycle arrest through the regulation of cyclins, the induction of p27Kip1, and the decrease CDK2 kinase activity. And up‐regulated p27Kip1 level is caused by protein stability increment by the reduction of S‐phase kinase‐associated protein 2 (Skp2), a key molecule related with p27Kip1 ubiquitination and degradation, and de novo protein synthesis. And an ethanol extract of RVS‐induced apoptosis via mitochondrial pathway was confirmed by previously. Therefore, an ethanol extract of RVS induces G1‐cell cycle arrest via accumulation of p27Kip1 controlled by Skp2 reduction in human gastric cancer cells but not in normal cells, therefore we suggest that this extract could be a candidate medicine or compound for the development of novel class of anti‐cancer drug.