Emodin inhibits tumor cell migration through suppression of the phosphatidylinositol 3-kinase-Cdc42/Rac1 pathway
Emodin inhibits tumor cell migration through suppression of the phosphatidylinositol 3-kinase-Cdc42/Rac1 pathway
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DOI：
10.1007/s00018-005-5050-2
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发表时间：
2005-05-01
影响因子：
8
通讯作者：
Ong, CN
中科院分区：
文献类型：
--
作者：
Huang, Q;Shen, HM;Ong, CN
增强的细胞迁移是癌症侵袭和转移的潜在机制之一。因此，抑制细胞迁移被认为是预防癌症转移的有效策略。我们发现大黄素（3-甲基-1，6，8-三羟基蒽醌），从大黄根茎的活性成分，显着抑制表皮生长因子（EGF）诱导的各种人类癌细胞系的迁移。在寻找潜在的分子机制时，我们证明了磷脂酰肌醇3-激酶（PI 3 K）是大黄素的分子靶点。此外，大黄素显着抑制EGF诱导的Cdc 42和Rac 1的激活和相应的细胞骨架的变化。此外，大黄素，而不是LY 294002，能够阻止细胞迁移与组成型活性（CA）-Cdc 42和CA-Rac 1转染细胞通过干扰Cdc 42/Rac 1和p21激活的激酶复合物的形成。综上所述，本研究的数据表明，大黄素通过抑制PI 3 K-Cdc 42/Rac 1信号通路抑制人类癌细胞迁移。
Enhanced cell migration is one of the underlying mechanisms in cancer invasion and metastasis. Therefore, inhibition of cell migration is considered to be an effective strategy for prevention of cancer metastasis. We found that emodin (3-methyl-1,6,8-trihydroxyanthraquinone), an active component from the rhizome of Rheum palmatum, significantly inhibited epidermal growth factor (EGF)-induced migration in various human cancer cell lines. In the search for the underlying molecular mechanisms, we demonstrated that phosphatidylinositol 3-kinase (PI3K) serves as the molecular target for emodin. In addition, emodin markedly suppressed EGF-induced activation of Cdc42 and Rac1 and the corresponding cytoskeleton changes. Moreover, emodin, but not LY294002, was able to block cell migration in cells transfected with constitutively active (CA)-Cdc42 and CA-Rac1 by interference with the formation of Cdc42/Rac1 and the p21-activated kinase complex. Taken together, data from this study suggest that emodin inhibits human cancer cell migration by suppressing the PI3K-Cdc42/Rac1 signaling pathway.