Effect of Kumatakenin Isolated From Cloves on the Apoptosis of Cancer Cells and the Alternative Activation of Tumor-Associated Macrophages

Abstract

The flower bud of Syzygium aromaticum (clove) has been used for centuries as a spice and herbal medicine. The biological activities of kumatakenin, a flavonoid that has recently been isolated from cloves, are poorly characterized. In the present study, the anticancer effects of kumatakenin in human ovarian cancer cells and tumor-associated macrophages (TAMs) were investigated. We found that kumatakenin exhibited significant cytotoxic activity in human ovarian cancer cells, SKOV3 and A2780. A propidium iodide and Annexin V-FITC staining assay showed that kumatakenin induces apoptosis in ovarian cancer cells. Kumatakenin treatment increased the activity of caspase-3, -8, and -9, and caspase inhibitors attenuated kumatakenin-induced SKOV3 cell death. In addition, kumatakenin was found to reduce the expressions of MCP-1 and RANTES, which are major determinants of macrophage recruitment at tumor sites in ovarian cancer cells. Moreover, kumatakenin inhibited the expression of M2 markers and cancer-promoting factors, including IL-10, MMP-2/-9, and VEGF, in macrophages stimulated by the ovarian cancer cells. In conclusion, these results suggest that kumatakenin shows anticancer activities by inducing apoptosis of ovarian cancer cells and inhibiting the alternative activation of TAM.