乾漆이 위암세포의 활성, 세포사멸 및 세포주기관련 유전자 발현에 미치는 영향
Effects of Rhus verniciflua Stokes Extract on Cell Viability, Cell Cycle Progression and Apoptosis of AGS Cell
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Abstract
The Rhus verniciflua Stokes (乾漆-RVS) has been used in traditional East Asia medicine for the therapy of gastritis, stomach cancer, although the mechanism for the biological activity is unclear. In the present study aims to investigate RVS extract contributes to growth inhibitory effect and it`s the molecular mechanism on the human gastric cancer cells. AGS (gastric cancer cells) and RIE1 (normal cells) were treated to different concentrations and periods of RVS extract (10 ~ 100 ug/mll). Growth inhibitory effect was analyzed by measuring FACS study and MTS assay. Cell cycle inhibition was confirmed by measuring CDK2 kinase activity by immunoprecipitation and kinase assay. And apoptosis was confirmed by surveying caspase cascades activation using a pan caspase inhibitor. Exposure to RVS extract (50 ug/mll) resulted in a synergistic inhibitory effect on cell growth in AGS cells. Growth inhibition was related with the inhibition of proliferation and induction of apoptosis. The extract induces G1-cell cycle arrest through the regulation of cyclins, the induction of p27Kip1, and the decrease CDK2 kinase activity. And upregulated 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. Besides, 乾漆 extract induces apoptosis through the expression of Bax, poly(ADP-ribose) polymerase (PARP) and activation of caspase-3. RVS extract induces G1-cell cycle arrest via accumulation of p27Kip1 and apoptosis in human gastric cancer cells but not in normal cells, therefore we suggest that the extract can be used as a novel class of anti-cancer drugs.
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