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

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.

Sulforaphane Inhibits Growth of Human Breast Cancer Cells and Augments the Therapeutic Index of the Chemotherapeutic Drug, Gemcitabine

“…This implies that sulforaphane enhances the efficiency of gemcitabine against the cancer cells, especially at lower doses, thereby minimizing its cytotoxicity to normal cells resulting in better survival. Other studies have also reported a synergistic interaction between different treatment strategies (Liu et al, 2001;Kuhar et al, 2007;Kumi-Diaka et al, 2010;Wang et al, 2011). Other studies of concurrent curcumin and chemotherapeutic drugs such as cisplatin, doxorubicin, and taxol showed that curcumin enhances the antitumor activities of the latter in various cancer cells (Chan et al, 2003;Notarbartolo et al, 2005).…”

Cancer chemoprevention and chemotherapy: Dietary polyphenols and signalling pathways

“…EGCG has also shown beneficial effects in lung cancer by decreasing the growth of the primary tumours and metastasis when mice were intraperitoneally (i.p.) injected with B16-F3m cells [37]; however, rats with breast cancer did not improve after receiving EGCG in the drinking water [26].…”

Green tea catechin, epigallocatechin‐3‐gallate, inhibits vascular endothelial growth factor angiogenic signaling by disrupting the formation of a receptor complex

“…VEGF-induced signaling pathway activation is required for the biological outcomes of stimulated endothelial cell proliferation and tube formation. [10][11][12] IL-8 is a cytokine produced by a variety of cells types, including transformed and endothelial cells. In addition to being a chemotactic cytokine, IL-8 is a potent angiogenic factor in vivo and in vitro.…”