Moscatilin inhibits migration and metastasis of human breast cancer MDA-MB-231 cells through inhibition of Akt and Twist signaling pathway

Hui Chen Pai, Li Hsun Chang, Chieh Yu Peng, Ya Ling Chang, Chien Chih Chen, Chien Chang Shen, Che Ming Teng, Shiow Lin Pan

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)347-356
Number of pages10
JournalJournal of Molecular Medicine
Volume91
Issue number3
DOIs
Publication statusPublished - Mar 2013

Fingerprint

Breast Neoplasms
Neoplasm Metastasis
Cell Movement
Lung
dendrophenol
Twist-Related Protein 1
Cell Migration Inhibition
Epithelial-Mesenchymal Transition
Cadherins
Neoplasms
Radiotherapy
Animal Models
Phosphorylation
Weights and Measures
Drug Therapy
Messenger RNA

Keywords

  • Breast cancer
  • Migration
  • Moscatilin
  • Twist

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

Cite this

Moscatilin inhibits migration and metastasis of human breast cancer MDA-MB-231 cells through inhibition of Akt and Twist signaling pathway. / Pai, Hui Chen; Chang, Li Hsun; Peng, Chieh Yu; Chang, Ya Ling; Chen, Chien Chih; Shen, Chien Chang; Teng, Che Ming; Pan, Shiow Lin.

In: Journal of Molecular Medicine, Vol. 91, No. 3, 03.2013, p. 347-356.

Research output: Contribution to journalArticle

Pai, Hui Chen ; Chang, Li Hsun ; Peng, Chieh Yu ; Chang, Ya Ling ; Chen, Chien Chih ; Shen, Chien Chang ; Teng, Che Ming ; Pan, Shiow Lin. / Moscatilin inhibits migration and metastasis of human breast cancer MDA-MB-231 cells through inhibition of Akt and Twist signaling pathway. In: Journal of Molecular Medicine. 2013 ; Vol. 91, No. 3. pp. 347-356.
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AU - Chen, Chien Chih

AU - Shen, Chien Chang

AU - Teng, Che Ming

AU - Pan, Shiow Lin

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AB - 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.

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