Oridonin induces apoptosis and senescence by increasing hydrogen peroxide and glutathione depletion in colorectal cancer cells.
Oridonin induces apoptosis and senescence by increasing hydrogen peroxide and glutathione depletion in colorectal cancer cells.
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冬凌草甲素通过增加结直肠癌细胞中过氧化氢和谷胱甘肽的消耗来诱导细胞凋亡和衰老
DOI：
10.3892/ijmm.2012.895
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发表时间：
2012-04
影响因子：
5.4
通讯作者：
Wu YL
中科院分区：
文献类型：
--
作者：
Gao FH;Liu F;Wei W;Liu LB;Xu MH;Guo ZY;Li W;Jiang B;Wu YL
我们最近在体内外证实冬凌草甲素可以诱导结肠癌细胞的凋亡和衰老。然而，其潜在的机制仍不清楚。在这项研究中，研究了活性氧在冬凌草甲素诱导的结肠腺癌SW1116细胞死亡和衰老中的作用。冬凌草甲素以剂量依赖的方式增加细胞内过氧化氢水平，降低谷胱甘肽含量。活性氧清除剂N-乙酰半胱氨酸不仅能阻断冬凌草甲素诱导的过氧化氢和谷胱甘肽耗竭的增加，而且还能阻断冬凌草甲素诱导的细胞凋亡和衰老，表现为膜联蛋白V和衰老相关β半乳糖苷酶阳性细胞的减少，抑制冬凌草甲素诱导的p53和p16表达上调和c-Myc表达下调。此外，外源过氧化氢酶能抑制冬凌草甲素诱导的过氧化氢增加和细胞凋亡，但不能抑制谷胱甘肽的耗竭和衰老。此外，冬凌草甲素在体外和细胞内均可降低硫氧还蛋白还原酶(TrxR)的活性，这可能是导致过氧化氢增加的原因之一。综上所述，过氧化氢和谷胱甘肽耗竭的增加是冬凌草甲素诱导结直肠癌细胞凋亡和衰老的原因，TrxR抑制参与了这一过程。鉴于TrxR作为结肠癌新的肿瘤靶点的重要性，冬凌草甲素将是一个有前途的临床候选药物。冬凌草甲素抑制TrxR的机制值得进一步研究。
We recently demonstrated that oridonin could induce apoptosis and senescence of colon cancer cells in vitro and in vivo. However, the underlying mechanism remains unknown. In this study, the involvement of reactive oxygen species in oridonin-induced cell death and senescence was investigated in colon adenocarcinoma-derived SW1116 cells. Oridonin increased intracellular hydrogen peroxide levels and reduced the glutathione content in a dose-dependent manner. N-acetylcysteine, a reactive oxygen species scavenger, not only blocked the oridonin-induced increase in hydrogen peroxide and glutathione depletion, but also blocked apoptosis and senescence induced by oridonin, as evidenced by the decrease in Annexin V and senescence-associated β-galactosidase- positive cells and the inhibition of oridonin-induced upregulation of p53 and p16 and downregulation of c-Myc. Moreover, exogenous catalase could inhibit the increase in hydrogen peroxide and apoptosis induced by oridonin, but not the glutathione depletion and senescence. Furthermore, thioredoxin reductase (TrxR) activity was reduced by oridonin in vitro and in cells, which may cause the increase in hydrogen peroxide. In conclusion, the increase in hydrogen peroxide and glutathione depletion account for oridonin-induced apoptosis and senescence in colorectal cancer cells, and TrxR inhibition is involved in this process. Given the importance of TrxR as a novel cancer target in colon cancer, oridonin would be a promising clinical candidate. The mechanism of oridonin-induced inhibition of TrxR warrants further investigation.
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影响因子：
2.6
作者：
Mukherjee, A.;Martin, S. G.
通讯作者：
Martin, S. G.
影响因子：
5
作者：
Sousa, Teresa;Pinho, Dora;Albino-Teixeira, Antonio
通讯作者：
Albino-Teixeira, Antonio
DOI：
10.1002/cyto.990150411
发表时间：
1994-04-01
期刊：
CYTOMETRY
影响因子：
--
作者：
HEDLEY, DW;CHOW, S
通讯作者：
CHOW, S
影响因子：
2.6
作者：
Jones, KR;Elmore, LW;Gewirtz, DA
通讯作者：
Gewirtz, DA
冬凌草甲素通过增加组蛋白高度乙酰化和 p16、p21、p27 和 c-myc 的调节来诱导结直肠癌细胞凋亡和衰老
影响因子：
3.8
作者：
Gao FH;Hu XH;Li W;Liu H;Zhang YJ;Guo ZY;Xu MH;Wang ST;Jiang B;Liu F;Zhao YZ;Fang Y;Chen FY;Wu YL
通讯作者：
Wu YL