Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan.
Food Chem Toxicol. 2012 Oct;50(10):3489-97. doi: 10.1016/j.fct.2012.06.046. Epub 2012 Jul 4.
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 μg/mL) arrested HL-60 cells at the G1-S transition phase through the reductions of Cyclin D1, CDK4, Cyclin E, CDK2, and Cyclin A, and induction of CDK inhibitor p27KIP levels. Furthermore, VEGF expression and release was significantly inhibited by TS 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 μg/mL), a major compound in TS, caused G1 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.
香椿是台湾地区最受欢迎的素食菜肴之一，已被证明可诱导培养的人早幼粒细胞白血病（HL-60）细胞凋亡。在本研究中，我们使用体外细胞培养和裸鼠模型研究了香椿叶提取物（TS 提取物）对肿瘤消退的影响。我们发现，TS 提取物（10-75μg/ml）通过降低细胞周期蛋白 D1、CDK4、细胞周期蛋白 E、CDK2 和细胞周期蛋白 A，并诱导 CDK 抑制剂 p27KIP 水平，将 HL-60 细胞阻滞在 G1-S 期。此外，TS 提取物显著抑制了 VEGF 的表达和释放。值得注意的是，TS 提取物治疗能有效延迟裸鼠接种 HL-60 细胞后的肿瘤发生率，并降低肿瘤负担。组织学分析证实，TS 提取物能显著调节异种移植瘤的肿瘤进展。此外，在 TS 中的主要化合物没食子酸（5 和 10μg/ml）也能通过调节细胞周期调节蛋白引起 G1 期阻滞，产生类似的结果。我们的数据表明，香椿主要通过没食子酸在体外和体内对 HL-60 细胞发挥抗增殖作用。
