Huang Q, Shen H-M, Ong C-N
Department of Community, Occupational, and Family Medicine, Faculty of Medicine, National University of Singapore.
Cell Mol Life Sci. 2005 May;62(10):1167-75. doi: 10.1007/s00018-005-5050-2.
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.
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，大黄根茎中的活性成分大黄素（3-甲基-1,6,8-三羟基蒽醌）能显著抑制表皮生长因子（EGF）诱导的多种人类癌细胞系的迁移。在探寻其潜在分子机制的过程中，我们证明磷脂酰肌醇3-激酶（PI3K）是大黄素的分子靶点。此外，大黄素显著抑制EGF诱导的Cdc42和Rac1激活以及相应的细胞骨架变化。而且，大黄素能够通过干扰Cdc42/Rac1和p21激活激酶复合物的形成，阻断组成型激活（CA）-Cdc42和CA-Rac1转染细胞中的细胞迁移，而LY294002则不能。综上所述，本研究数据表明大黄素通过抑制PI3K-Cdc42/Rac1信号通路来抑制人类癌细胞迁移。
