Pharmacologic doses of ascorbic acid repress specificity protein (Sp) transcription factors and Sp-regulated genes in colon cancer cells.
Pharmacologic doses of ascorbic acid repress specificity protein (Sp) transcription factors and Sp-regulated genes in colon cancer cells.
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DOI：
10.1080/01635581.2011.605984
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Safe S
中科院分区：
文献类型：
--
作者：
Pathi SS;Lei P;Sreevalsan S;Chadalapaka G;Jutooru I;Safe S
抗坏血酸（维生素 C）可抑制癌细胞生长，并且这种具有促氧化活性的化合物的药理学剂量的癌症化学保护作用存在争议。我们假设药理剂量的抗坏血酸 (< 5 mM) 的抗癌活性部分归因于活性氧 (ROS) 依赖性特异性蛋白 (Sp) 转录因子 Sp1、Sp3 和 Sp4 以及 Sp 调节基因的下调。在这项研究中，抗坏血酸 (1 – 3 mM) 降低了 RKO 和 SW480 结肠癌细胞增殖并诱导细胞凋亡和坏死，同时伴随着 Sp1、Sp3 和 Sp4 蛋白的下调。此外，抗坏血酸降低了几种与癌症增殖[肝细胞生长因子受体（c-Met）、表皮生长因子受体（EGFR）和细胞周期蛋白D1]、生存（生存素和bcl-2）和血管生成[血管内皮生长因子（VEGF）及其受体（VEGFR1和VEGFR2）]相关的Sp调节基因的表达。其他促氧化剂（例如过氧化氢）在结肠癌细胞中表现出类似的活性，并且与谷胱甘肽共同治疗可抑制这些反应。这项研究首次证明抗坏血酸的抗癌活性部分归因于 ROS 依赖性 Sp 转录因子的抑制。
Ascorbic acid (vitamin C) inhibits cancer cell growth and there is a controversy regarding the cancer chemoprotective effects of pharmacologic doses of this compound which exhibits pro-oxidant activity. We hypothesized that the anticancer activity of pharmacologic doses of ascorbic acid (< 5 mM) is due, in part, to reactive oxygen species (ROS)-dependent downregulation of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 and Sp-regulated genes. In this study, ascorbic acid (1 – 3 mM) decreased RKO and SW480 colon cancer cell proliferation and induced apoptosis and necrosis and this was accompanied by downregulation of Sp1, Sp3 and Sp4 proteins. In addition, ascorbic acid decreased expression of several Sp-regulated genes that are involved in cancer proliferation [hepatocyte growth factor receptor (c-Met), epidermal growth factor receptor (EGFR) and cyclin D1], survival (survivin and bcl-2), and angiogenesis [vascular endothelial growth factor (VEGF) and its receptors (VEGFR1 and VEGFR2)]. Other pro-oxidants such as hydrogen peroxide exhibited similar activities in colon cancer cells and cotreatment with glutathione inhibited these responses. This study demonstrates for the first time that the anticancer activities of ascorbic acid are due, in part, to ROS-dependent repression of Sp transcription factors.
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影响因子：
6.4
作者：
Chintharlapalli, Sudhakar;Papineni, Sabitha;Abdelrahim, Maen;Abudayyeh, Ala;Jutooru, Indira;Chadalapaka, Gayathri;Wu, Fei;Mertens-Talcott, Susanne;Vanderlaag, Kathy;Cho, Sung Dae;Smith, Roger, III;Safe, Stephen
通讯作者：
Safe, Stephen
影响因子：
11.2
作者：
Chadalapaka G;Jutooru I;Chintharlapalli S;Papineni S;Smith R 3rd;Li X;Safe S
通讯作者：
Safe S
影响因子：
3.1
作者：
Kumar S;Sun X;Wiseman DA;Tian J;Umapathy NS;Verin AD;Black SM
通讯作者：
Black SM
影响因子：
158.5
作者：
CREAGAN, ET;MOERTEL, CG;FRYTAK, S
通讯作者：
FRYTAK, S
DOI：
10.1093/gerona/51a.1.b66
发表时间：
1996-01-01
影响因子：
5.1
作者：
Adrian, GS;Seto, E;Bowman, BH
通讯作者：
Bowman, BH