Curcumin Suppresses Metastasis via Sp-1, FAK Inhibition, and E-Cadherin Upregulation in Colorectal Cancer.
Curcumin Suppresses Metastasis via Sp-1, FAK Inhibition, and E-Cadherin Upregulation in Colorectal Cancer.
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DOI：
10.1155/2013/541695
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Yu SL
中科院分区：
文献类型：
--
作者：
Chen CC;Sureshbabul M;Chen HW;Lin YS;Lee JY;Hong QS;Yang YC;Yu SL
结直肠癌(CRC)是世界范围内由饮食变化和各种环境应激因素引起的严重公共卫生问题。姜黄素是一种用于治疗多种肿瘤的传统药物。然而，姜黄素抗结直肠癌转移的作用机制尚未完全阐明。在此，我们探讨了姜黄素在体内外抑制结直肠癌细胞转移的分子机制。姜黄素在体外显著抑制细胞的迁移、侵袭和集落形成，并在体内减少肿瘤生长和肝转移。我们发现姜黄素抑制Sp-1转录活性和Sp-1调控的基因，包括ADEM10、钙调蛋白、EPHB2、HDAC4和SEPP1。姜黄素抑制粘着斑激酶(FAK)的磷酸化，并增强在侵袭和转移中起关键作用的几种细胞外基质成分的表达。姜黄素以剂量依赖的方式降低结直肠癌细胞CD24的表达。此外，E-钙粘素的表达被姜黄素上调，并作为EMT的抑制因子。这些结果表明，姜黄素通过下调Sp-1、FAK和CD24的表达以及促进E-钙粘附素在结直肠癌细胞中的表达来发挥其抗转移作用。
Colorectal cancer (CRC) is a serious public health problem that results due to changes of diet and various environmental stress factors in the world. Curcumin is a traditional medicine used for treatment of a wide variety of tumors. However, antimetastasis mechanism of curcumin on CRC has not yet been completely investigated. Here, we explored the underlying molecular mechanisms of curcumin on metastasis of CRC cells in vitro and in vivo. Curcumin significantly inhibits cell migration, invasion, and colony formation in vitro and reduces tumor growth and liver metastasis in vivo. We found that curcumin suppresses Sp-1 transcriptional activity and Sp-1 regulated genes including ADEM10, calmodulin, EPHB2, HDAC4, and SEPP1 in CRC cells. Curcumin inhibits focal adhesion kinase (FAK) phosphorylation and enhances the expressions of several extracellular matrix components which play a critical role in invasion and metastasis. Curcumin reduces CD24 expression in a dose-dependent manner in CRC cells. Moreover, E-cadherin expression is upregulated by curcumin and serves as an inhibitor of EMT. These results suggest that curcumin executes its antimetastasis function through downregulation of Sp-1, FAK, and CD24 and by promoting E-cadherin expression in CRC cells.
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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
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作者：
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