Lipoxygenases are a family of iron-containing enzymes that catalyze the formation of hydroperoxides from polyunsaturated fatty acids. Esculetin is an inhibitor of both 5- and 12-lipoxygenases with ID50 values of 4 and 2.5 μM, respectively[3]. It shows inhibitory effect on platelet lipoxygenase and platelet cyclooxygenase with respective IC50 values of 0.65 and 0.45 μM[4]. Treatment of colon cancer cells with esculetin (20-80 μMol/L) for 24h effectively suppressed TOP-luciferase activity in a dose-dependent manner. In HCT116, HCT15, and DLD1 colon cancer cells, 24h- treatment of esculetin at the doses of 20 - 80 μM substantially inhibited the protein levels of c-Myc and cyclin D1, but had no effect on the expressions of β-catenin or Tcf. Consistently, the mRNA levels of c-myc and cyclin D1 in esculetin-treated human colon cancer cells was downregulated compared to control group. Moreover, esculetin at 20 - 80 μM decreased the viability of colon cancer cells, and significantly repressed anchorage-independent cell growth in a dose-dependent manner. In athymic nude mice, intraperitoneal injection of esculetin at 20 and 100 mg/kg (3 times per week) for 2 weeks suppressed HCT116 tumor size by 44% and 64%, respectively, compared to vehicle-treated group[5].
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