Moscatilin inhibits migration and metastasis of human breast cancer MDA-MB-231 cells through inhibition of Akt and Twist signaling pathway
Journal
Journal of Molecular Medicine
Journal Volume
91
Journal Issue
3
Pages
347-356
Date Issued
2013
Author(s)
CHE-MING TENG
Abstract
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. ? 2012 Springer-Verlag.
Subjects
Breast cancer; Migration; Moscatilin; Twist
SDGs
Other Subjects
moscatilin; nerve cell adhesion molecule; plant medicinal product; protein kinase B; transcription factor Snail; transcription factor Twist; unclassified drug; antineoplastic activity; article; breast cancer; breast metastasis; cell migration; controlled study; epithelial mesenchymal transition; human; human cell; in vitro study; in vivo study; lung metastasis; lung nodule; protein expression; protein phosphorylation; signal transduction; Animals; Benzyl Compounds; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Female; Gene Expression Regulation, Neoplastic; Humans; Mice; Neoplasm Metastasis; Nuclear Proteins; Proto-Oncogene Proteins c-akt; Signal Transduction; Transcription Factors; Twist Transcription Factor
Type
journal article