Inhibition of melanoma growth and metastasis by combination with (-)-epigallocatechin-3-gallate and dacarbazine in mice

Jean-Dean Liu, Sheng-Hsuan Chen, Chih Li Lin, Shu-Huei Tsai, Yu-Chih Liang

Research output: Contribution to journalArticle

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Abstract

(-)-Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, was shown to have cancer chemopreventive activity. In this study, we examined the antimetastatic effects of EGCG or the combination of EGCG and dacarbazine on B16-F3m melanoma cells in vitro and in vivo. First, the antimetastatic potentials of five green tea catechins were examined by soft agar colony formation assay, and the results show that EGCG was more effective than the other catechins in inhibiting soft agar colony formation. Second, EGCG dose-dependently inhibited B16-F3m cell migration and invasion by in vitro Transwell assay. Third, EGCG significantly inhibited the spread of B16-F3m cells on fibronectin, laminin, collagen, and Matrigel in a dose-dependent manner. In addition, EGCG significantly inhibited the tyrosine phosphorylation of focal adhesion kinase (FAK) and the activity of matrix metalloproteinase-9 (MMP-9). In animal experiments, EGCG alone reduced lung metastases in mice bearing B16-F3m melanomas. However, a combination of EGCG and dacarbazine was more effective than EGCG alone in reducing the number of pulmonary metastases and primary tumor growths, and increased the survival rate of melanoma-bearing mice. These results demonstrate that combination treatment with EGCG and dacarbazine strongly inhibits melanoma growth and metastasis, and the action mechanisms of EGCG are associated with the inhibition of cell spreading, cell-extracellular matrix and cell-cell interactions, MMP-9 and FAK activities.

Original languageEnglish
Pages (from-to)631-642
Number of pages12
JournalJournal of Cellular Biochemistry
Volume83
Issue number4
DOIs
Publication statusPublished - 2001

Fingerprint

Dacarbazine
Melanoma
Neoplasm Metastasis
Growth
Bearings (structural)
Focal Adhesion Protein-Tyrosine Kinases
Experimental Melanomas
Catechin
Matrix Metalloproteinase 9
Tea
Agar
epigallocatechin gallate
Assays
Lung
Phosphorylation
Polyphenols
Laminin
Fibronectins
Cell Communication
Cell Movement

Keywords

  • Dacarbazine
  • EGCG
  • Invasion
  • Melanoma
  • Metastasis

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Inhibition of melanoma growth and metastasis by combination with (-)-epigallocatechin-3-gallate and dacarbazine in mice. / Liu, Jean-Dean; Chen, Sheng-Hsuan; Lin, Chih Li; Tsai, Shu-Huei; Liang, Yu-Chih.

In: Journal of Cellular Biochemistry, Vol. 83, No. 4, 2001, p. 631-642.

Research output: Contribution to journalArticle

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AU - Tsai, Shu-Huei

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AB - (-)-Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, was shown to have cancer chemopreventive activity. In this study, we examined the antimetastatic effects of EGCG or the combination of EGCG and dacarbazine on B16-F3m melanoma cells in vitro and in vivo. First, the antimetastatic potentials of five green tea catechins were examined by soft agar colony formation assay, and the results show that EGCG was more effective than the other catechins in inhibiting soft agar colony formation. Second, EGCG dose-dependently inhibited B16-F3m cell migration and invasion by in vitro Transwell assay. Third, EGCG significantly inhibited the spread of B16-F3m cells on fibronectin, laminin, collagen, and Matrigel in a dose-dependent manner. In addition, EGCG significantly inhibited the tyrosine phosphorylation of focal adhesion kinase (FAK) and the activity of matrix metalloproteinase-9 (MMP-9). In animal experiments, EGCG alone reduced lung metastases in mice bearing B16-F3m melanomas. However, a combination of EGCG and dacarbazine was more effective than EGCG alone in reducing the number of pulmonary metastases and primary tumor growths, and increased the survival rate of melanoma-bearing mice. These results demonstrate that combination treatment with EGCG and dacarbazine strongly inhibits melanoma growth and metastasis, and the action mechanisms of EGCG are associated with the inhibition of cell spreading, cell-extracellular matrix and cell-cell interactions, MMP-9 and FAK activities.

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