Anti-cancer effect of thiacremonone through down regulation of peroxiredoxin 6.
Anti-cancer effect of thiacremonone through down regulation of peroxiredoxin 6.
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DOI：
10.1371/journal.pone.0091508
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Hong JT
中科院分区：
文献类型：
--
作者：
Jo M;Yun HM;Park KR;Park MH;Lee DH;Cho SH;Yoo HS;Lee YM;Jeong HS;Kim Y;Jung JK;Hwang BY;Lee MK;Kim ND;Han SB;Hong JT
Thiacremonone（2,4 -二羟基- 2,5 -二甲基-噻吩-3- 1）是由高温高压处理大蒜中生成的新型含硫化合物，是一种抗氧化剂。过氧化物还蛋白6 （PRDX6）是过氧化物酶的一个成员，具有谷胱甘肽过氧化物酶和钙非依赖性磷脂酶A2 （iPLA2）活性。一些研究表明，PRDX6通过增加谷胱甘肽过氧化物酶活性来刺激肺癌细胞的生长。对接模型研究和下拉实验表明，硫胺酮完全契合PRDX6谷胱甘肽过氧化物酶活性位点（cys-47），并与PRDX6相互作用。因此，我们研究噻肾上腺素是否通过阻断人肺癌细胞A549和NCI-H460中PRDX6谷胱甘肽过氧化物酶抑制细胞生长。Thiacremonone （0 ~ 50 μg/ml）通过诱导凋亡细胞死亡，同时诱导cleaved caspase-3、-8、-9、Bax、p21和p53表达，抑制肺癌细胞生长，呈浓度依赖性，但抑制xIAP、cIAP和Bcl2表达。硫胺酮进一步抑制肺癌细胞谷胱甘肽过氧化物酶活性。然而，在转染突变体PRDX6 （C47S）的肺癌细胞中，在二硫苏糖醇和谷胱甘肽存在的情况下，未观察到硫肾上腺素对细胞生长的抑制作用。在同种异体移植体内模型中，硫胺酮（30 mg/kg）也抑制肿瘤生长，降低PRDX6表达和谷胱甘肽过氧化物酶活性，但增加了cleaved caspase-3、-8、-9、Bax、p21和p53的表达。这些数据表明，硫肾上腺素通过相互作用抑制PRDX6的谷胱甘肽过氧化物酶活性来抑制肿瘤生长。这些数据表明，硫肾上腺素可能对肺癌有潜在的有益作用。
Thiacremonone (2, 4-dihydroxy-2, 5-dimethyl-thiophene-3-one) is an antioxidant substance as a novel sulfur compound generated from High-Temperature-High-Pressure-treated garlic. Peroxiredoxin 6 (PRDX6) is a member of peroxidases, and has glutathione peroxidase and calcium-independent phospholipase A2 (iPLA2) activities. Several studies have demonstrated that PRDX6 stimulates lung cancer cell growth via an increase of glutathione peroxidase activity. A docking model study and pull down assay showed that thiacremonone completely fits on the active site (cys-47) of glutathione peroxidase of PRDX6 and interacts with PRDX6. Thus, we investigated whether thiacremonone inhibits cell growth by blocking glutathione peroxidase of PRDX6 in the human lung cancer cells, A549 and NCI-H460. Thiacremonone (0–50 μg/ml) inhibited lung cancer cell growth in a concentration dependent manner through induction of apoptotic cell death accompanied by induction of cleaved caspase-3, -8, -9, Bax, p21 and p53, but decrease of xIAP, cIAP and Bcl2 expression. Thiacremonone further inhibited glutathione peroxidase activity in lung cancer cells. However, the cell growth inhibitory effect of thiacremonone was not observed in the lung cancer cells transfected with mutant PRDX6 (C47S) and in the presence of dithiothreitol and glutathione. In an allograft in vivo model, thiacremonone (30 mg/kg) also inhibited tumor growth accompanied with the reduction of PRDX6 expression and glutathione peroxidase activity, but increased expression of cleaved caspase-3, -8, -9, Bax, p21 and p53. These data indicate that thiacremonone inhibits tumor growth via inhibition of glutathione peroxidase activity of PRDX6 through interaction. These data suggest that thiacremonone may have potentially beneficial effects in lung cancer.
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影响因子：
4.8
作者：
Chatterjee, Shampa;Feinstein, Sheldon I.;Fisher, Aron B.
通讯作者：
Fisher, Aron B.
影响因子：
2.8
作者：
Druesne-Pecollo, Nathalie;Latino-Martel, Paule
通讯作者：
Latino-Martel, Paule
影响因子：
5.7
作者：
Ho, Jin-Nyoung;Lee, Seung Bum;Um, Hong-Duck
通讯作者：
Um, Hong-Duck
鉴定过氧蛋白6在乳腺癌进展中的功能作用。
DOI：
10.1186/bcr1789
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Chang XZ;Li DQ;Hou YF;Wu J;Lu JS;Di GH;Jin W;Ou ZL;Shen ZZ;Shao ZM
通讯作者：
Shao ZM
影响因子：
4.8
作者：
Kang, SW;Baines, IC;Rhee, SG
通讯作者：
Rhee, SG