Phamacological Institute, College of Medicine, National Taiwan University, No. 1, Jen-Ai Road, Sec. 1, Taipei, Taiwan.
J Mol Med (Berl). 2013 Mar;91(3):347-56. doi: 10.1007/s00109-012-0945-5. Epub 2012 Sep 8.
Breast cancer metastasis is more resistant to chemotherapy and radiotherapy than is cancer of the visceral tissues; therefore, new treatment strategies are urgently needed. Moscatilin, derived from the orchid Dendrobrium loddigesii, has shown anticancer activity. We evaluated the mechanism by which moscatilin suppresses the migration and metastasis of human breast cancer MDA-MB-231 cells in vitro and in vivo. We demonstrated that moscatilin significantly inhibits MDA-MB-231 cell migration by using scratch assays and Boyden chambers. Transcriptional factors inducing epithelial-mesenchymal transition, such as Twist, Snail, and Akt, play important roles in cell migration and cancer metastasis. Moscatilin inhibited the mRNA and protein expression of Twist, but not that of Snail, and subsequently inhibited N-cadherin expression. However, these effects were reversed by constitutively expressing active myristoylated (myr)-Akt and Twist overexpression. Moscatilin also suppressed Akt phosphorylation. However, Akt overexpression reversed the inhibitory effects of moscatilin on phospho-Akt protein expression but not its effects on Twist. The moscatilin-mediated inhibition of cell migration was reversed by Akt and Twist overexpression, demonstrating that moscatilin blocked cell migration by inhibiting Akt and Twist. In an MDA-MB-231 metastatic animal model, moscatilin (100 mg/kg) significantly suppressed breast cancer metastasis to the lungs and reduced the number of metastatic lung nodules and lung weight without causing any toxicity. These results indicated that moscatilin inhibited MDA-MB-231 cell migration via Akt- and Twist-dependent pathways; this finding was consistent with moscatilin's antimetastatic activity in vivo. Therefore, moscatilin may be an effective compound for the prevention of human breast cancer metastasis.
乳腺癌转移比内脏组织的癌症对化疗和放疗更具抵抗力；因此，迫切需要新的治疗策略。从兰科石斛中提取的木犀草素具有抗癌活性。我们评估了木犀草素在体外和体内抑制人乳腺癌 MDA-MB-231 细胞迁移和转移的机制。我们通过划痕实验和 Boyden 室证实木犀草素显著抑制 MDA-MB-231 细胞迁移。诱导上皮-间充质转化的转录因子，如 Twist、Snail 和 Akt，在细胞迁移和癌症转移中发挥重要作用。木犀草素抑制 Twist 的 mRNA 和蛋白表达，但不抑制 Snail 的表达，随后抑制 N-钙粘蛋白的表达。然而，这些效应被组成型表达有活性的肉豆蔻酰化（myr）-Akt 和 Twist 过表达所逆转。木犀草素还抑制 Akt 磷酸化。然而，Akt 过表达逆转了木犀草素对磷酸化 Akt 蛋白表达的抑制作用，但对 Twist 没有影响。Akt 和 Twist 的过表达逆转了木犀草素介导的细胞迁移抑制，表明木犀草素通过抑制 Akt 和 Twist 阻断细胞迁移。在 MDA-MB-231 转移性动物模型中，木犀草素（100mg/kg）显著抑制乳腺癌向肺部转移，减少转移性肺结节的数量和肺重，而没有引起任何毒性。这些结果表明，木犀草素通过 Akt 和 Twist 依赖性途径抑制 MDA-MB-231 细胞迁移；这一发现与木犀草素在体内的抗转移活性一致。因此，木犀草素可能是预防人类乳腺癌转移的有效化合物。
