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Journal of Molecular Medicine

, Volume 91, Issue 3, pp 347–356 | Cite as

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 TengEmail author
  • Shiow-Lin PanEmail author
Original Article

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.

Keywords

Moscatilin Breast cancer Migration Twist 

Notes

Acknowledgments

This study was supported by grants from the National Science Council of Taiwan (NSC 99-2320-B400-008-MY3) and (NSC 99-2628-B002-024-MY3).

Supplementary material

109_2012_945_MOESM1_ESM.pdf (236 kb)
ESM 1 (PDF 235 kb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Hui-Chen Pai
    • 1
  • Li-Hsun Chang
    • 1
  • Chieh-Yu Peng
    • 2
    • 3
  • Ya-Ling Chang
    • 1
  • Chien-Chih Chen
    • 4
  • Chien-Chang Shen
    • 5
  • Che-Ming Teng
    • 1
    Email author
  • Shiow-Lin Pan
    • 6
    • 7
    Email author
  1. 1.Phamacological Institute, College of MedicineNational Taiwan UniversityTaipeiTaiwan
  2. 2.Natural Medicinal Products Research CenterChina Medical University HospitalTaichungTaiwan
  3. 3.School of Chinese MedicineChina Medical UniversityTaichungTaiwan
  4. 4.Department of BiotechnologyHungkuang UniversityTaichungTaiwan
  5. 5.National Research Institute of Chinese MedicineTaipeiTaiwan
  6. 6.Institute of Biotechnology and Pharmaceutical ResearchNational Health Research InstitutesZhunanTaiwan
  7. 7.Department of PharmacologyTaipei Medical UniversityTaipeiTaiwan

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