Role of cyclin inhibitor protein p21 in the inhibition of HCT116 human colon cancer cell proliferation by American ginseng (Panax quinquefolius) and its constituents.
Role of cyclin inhibitor protein p21 in the inhibition of HCT116 human colon cancer cell proliferation by American ginseng (Panax quinquefolius) and its constituents.
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DOI：
10.1016/j.phymed.2009.06.008
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发表时间：
2010-03
期刊：
影响因子：
7.9
通讯作者：
Murphy, L. L.
中科院分区：
文献类型：
--
作者：
King, M. L.;Murphy, L. L.
西洋参及其人参皂苷成分已被证明具有抗癌作用，但其作用机制尚不清楚。本研究采用野生型和p21−/−人结肠癌细胞模型，研究了人参(GE)及其人参皂苷(GF)和多糖组分(PS)对人结肠癌细胞增殖的影响，并探讨了p21在这些作用中的作用。Ge、GF和PS对野生型和p21−/−细胞的增殖均有抑制作用，且对野生型和p21−/−细胞更为敏感。Ge处理后野生型细胞停滞于G0/G1期，P53和p21蛋白表达增加，磷酸化MEK水平降低。相反，p21缺失的细胞显示细胞活力降低，死亡细胞数量增加，Bax和裂解的caspase-3蛋白表达增加。多糖和人参皂苷似乎都与GE的抗增殖和促凋亡作用有关。这项研究表明，p21能够阻止GE处理的HCT116野生型细胞，而p21缺陷的细胞以人参成分依赖的方式经历细胞死亡。
American ginseng and its ginsenoside constituents have been shown to exert anti-cancer effects although the mechanism of action remains unclear. The present study determined the effects of water-extracted ginseng (GE) or its ginsenoside (GF) and polysaccharide (PS) fractions on the proliferation of human colon cancer cells and examined the role of p21 in mediating these effects using wild-type and p21−/− HCT116 human colon carcinoma cells. Proliferation was inhibited by GE, GF, and PS in wild-type and p21−/− cells, and the p21−/− cells were more sensitive to these treatments. Wild type cells treated with GE were arrested in the G0/G1 phase of the cell cycle and the expression of p53 and p21 proteins was increased while phospho-MEK levels decreased. In contrast, cells deficient in p21 displayed reduced cell viability, elevated number of dead cells, and increased expression of Bax and cleaved caspase-3 proteins. Both polysaccharides and ginsenosides appear to be responsible for the anti-proliferative and proapoptotic effects of GE. This study suggests that p21 functions to arrest HCT116 wild-type cells treated with GE, while p21-deficient cells undergo cell death in a ginseng constituent-dependent manner.
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