Cytotoxic activities of 4 natural products – carnosic acid, xanthohumol, caffeic acid phenethyl ester and (-) eburnamonine

In a cytotoxic or anti-proliferation assay, 20 compounds derived from natural products have been screened for cytotoxic effects against A549 cell line using MTT assay. Among them, carnosic acid, xanthohumol, caffeic acid phenethyl ester and (-) eburnamonine showed activies at concentrations of 50µM and 10µM. These four active compounds were subjected to cytotoxicity studies in two other cell lines (A431 and SK-BR3), using SRB assay. While carnosic acid, xanthohumol and (-) eburnamonine still showed cytotoxic activity, caffeic acid phenethyl ester showed no activity in A431 cell line and low activity against SK-BR3 cell line (IC₅₀=258µM). Xanthohumol possessed the strongest cytotoxic effects against all 3 cell lines with IC₅₀ values of 24.16µM, 16.14µM and 1.68µM in A549, A431 and SK-BR3 cells, respectively. Because A431 and SK-BR3 cells are known to over-express tyrosine kinase receptors, we have studied the four compounds for KDR and Her2 tyrosine kinase receptor inhibitory activity by using fluorescence polarization. The results showed that except caffeic acid phenethyl ester, which showed low inhibitory activity on KDR at a high concentration of 10µM, the other compounds were inactive. In conclusion, carnosic acid, xanthohumol and (-) eburnamonine showed cytotoxic activity in A549, A431 and SK-BR3 cell lines but their activities are not mediated though the inhibition of KDR or Her2 receptors. The cytotoxic activity of caffeic acid phenethyl ester is just limited to A549 cell line, not for the other two cell lines, which suggests a specific activity of this compound.

Acknowledgement: This study was supported by a grant from the Ministry of Commerce, Industry and Energy (MOCIE) and the Korea Institute of Industrial Technology Evaluation & Planning (ITEP) through the Biohealth Products Research Center (BPRC) of Inje University.

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