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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 한국미생물생명공학회 Journal of Microbiology and Biotechnology Journal of Microbiology and Biotechnology 제26권 제2호
- 발행연도
- 2016.1
- 수록면
- 287 - 294 (8page)
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초록· 키워드
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The effect of kaempferol (3,5,7,4-tetrahydroxyflavone), a flavonoid compound that was identified in barnyard millet (Echinochloa crus-galli var. frumentacea) grains, on G2-checkpoint and apoptotic pathways was investigated in human acute leukemia Jurkat T cell clones stably transfected with an empty vector (J/Neo) or a Bcl-xL expression vector (J/Bcl-xL). Exposure of J/Neo cells to kaempeferol caused cytotoxicity and activation of the ATM/ATR-Chk1/Chk2 pathway, activating the phosphorylation of p53 (Ser-15), inhibitory phosphorylation of Cdc25C (Ser-216), and inactivation of cyclin-dependent kinase 1 (Cdk1), with resultant G2- arrest of the cell cycle. Under these conditions, apoptotic events, including upregulation of Bak and PUMA levels, Bak activation, mitochondrial membrane potential (Δψm) loss, activation of caspase-9, -8, and -3, anti-poly (ADP-ribose) polymerase (PARP) cleavage, and accumulation of apoptotic sub-G1 cells, were induced without accompanying necrosis. However, these apoptotic events, except for upregulation of Bak and PUMA levels, were completely abrogated in J/Bcl-xL cells overexpressing Bcl-xL, suggesting that the G2-arrest and the Bcl-xL-sensitive mitochondrial apoptotic events were induced, in parallel, as downstream events of the DNA-damage-mediated G2-checkpoint activation. Together these results demonstrate that kaempferol-mediated antitumor activity toward Jurkat T cells was attributable to G2-checkpoint activation, which caused not only G2-arrest of the cell cycle but also activating phosphorylation of p53 (Ser-15) and subsequent induction of mitochondriadependent apoptotic events, including Bak and PUMA upregulation, Bak activation, Δψm loss, and caspase cascade activation.
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참고문헌 (35)
참고문헌 신청
Abraham RT / 2001 / Cell cycle checkpoint signaling through the ATM and ATR kinases / Genes Dev 15:2177~2196
Berger A / 2013 / Kaempferol, a new nutrition-derived pan-inhibitor of human histone deacetylases / J. Nutr. Biochem 24:977~985
Blomgran R / 2007 / Cathepsin-cleaved Bid promotes apoptosis in human neutrophils via oxidative stress-induced lysosomal membrane permeabilization / J. Leukoc. Biol 81:1213~1223
Chipuk JE / 2008 / How do BCL-2 proteins induce mitochondrial outer membrane permeabilization / Trends Cell Biol 18:157~164
최은정 / 2008 / Kaempferol induced the apoptosis via cell cycle arrest in human breast cancer MDA-MB-453 cells / Nutrition Research and Practice 2(4):322~325
Berger A / 2013 / Kaempferol, a new nutrition-derived pan-inhibitor of human histone deacetylases / J. Nutr. Biochem 24:977~985
Blomgran R / 2007 / Cathepsin-cleaved Bid promotes apoptosis in human neutrophils via oxidative stress-induced lysosomal membrane permeabilization / J. Leukoc. Biol 81:1213~1223
Chipuk JE / 2008 / How do BCL-2 proteins induce mitochondrial outer membrane permeabilization / Trends Cell Biol 18:157~164
최은정 / 2008 / Kaempferol induced the apoptosis via cell cycle arrest in human breast cancer MDA-MB-453 cells / Nutrition Research and Practice 2(4):322~325
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