Cytotoxic constituents of Hydrangea angustipetala on human gastric carcinoma cells

Hydrangea angustipetala Hayata (Saxifragaceae) is an anti-malaria folk medicine and grows in mountains of northern Taiwan. The leaves of H. angustipetala were extracted with 70% acetone and column chromatography was combined with cytotoxic bioassay-guided fractionation to isolate the cytotoxic compounds. The Diaion HP-20 column 40% MeOH eluted fraction (D40M) of H. angustipetala inhibited the growth of P-388D₁ cells in vitro and prolonged the survival days of P-388D₁-bearing CDF1 mice. Furthermore, (+)-febrifugine (1) and trans-3-p-coumaroylquinic acid (2) were isolated from the D40M, and both compounds induced apoptosis in AGS and SNU-1 cells. However, the cytotoxicity of 1 was stronger than 2 and IC₅₀ values of 1 were 0.17 and 0.05 μg/ml in AGS and SNU-1 cells after treatment for 48 h, respectively. The two compounds both induced decreases in PARP and pro-caspase 3 of AGS and SNU-1 cells, and pre-treatment of cells with a caspase-3-specific inhibitor reduced cytotoxicity by 1 and 2 in AGS and SNU-1 cells. We suggested that the activation of caspase-3 may provide a mechanistic explanation for their (1 and 2) cytotoxic effects in AGS and SNU-1 cells. (+)-Febrifugine was a good lead compound as development an anticancer drug.