In vitro and in vivo activity of gallic acid and Toona sinensis leaf extracts against HL-60 human premyelocytic leukemia

Toona sinensis is one of the most popular vegetarian cuisines in Taiwan and it has been shown to induce apoptosis in cultured human premyelocytic leukemia (HL-60) cells. In the present study, we examined the effects of T. sinensis leaf extracts (TS extracts) on tumor regression using in vitro cell culture and an in vivo athymic nude mice model. We found that TS extracts (10-75 mu g/mL) arrested HL-60 cells at the G(1)-S transition phase through the reductions of Cyclin D1, CDK4, Cyclin E, CDK2, and Cyclin A. and induction of CDK inhibitor p27(KIP) levels. Furthermore, VEGF expression and release was significantly inhibited by IS extracts. Notably, TS extracts treatment was effective in terms of delaying tumor incidence in the nude mice inoculated with HL-60 cells as well as reducing the tumor burden. Histological analysis confirmed that TS extracts significantly modulated tumor progression in xenograft tumor. Furthermore, a similar pattern of results were observed from gallic acid (5 and 10 mu g/mL), a major compound in TS, caused G(1) arrest through regulations of cell-cycle regulatory proteins. Our data suggest that T. sinensis exerts antiproliferative effects on HL-60 cells in vitro and in vivo due mainly to the presence of gallic acid. (C) 2012 Elsevier Ltd. All rights reserved.