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.