Department of Biotechnology, Chungju National University, Chungju, Chungbuk 380-702, South Korea; Department of Food Science and Technology, Chung-Ang University, Ansung 72-1, Korea.
Phytother Res. 2010 Dec;24(12):1870-6. doi: 10.1002/ptr.3214.
The thorns of Gleditsia sinensis are used as a medicinal herb in China and Korea. However, the mechanisms responsible for the antitumor effects of the water extract of Gleditsia sinensis thorns (WEGS) remain unknown. HCT116 cells treated with the WEGS at a dose of 800 μg/mL (IC₅₀) showed a significant decrease in cell growth and an increase in cell cycle arrest during the G2/M-phase. G2/M-phase arrest was correlated with increased p53 levels and down-regulation of the check-point proteins, cyclinB1, Cdc2 and Cdc25c. In addition, treatment with WEGS induced phosphorylation of extracellular signal-regulated kinase (ERK), p38 MAP kinase and JNK (c-Jun N-terminal kinases). Moreover, inhibition of ERK by treatment of cells with the ERK-specific inhibitor PD98059 blocked WEGS-mediated p53 expression. Similarly, blockage of ERK function in the WEGS-treated cells reversed cell-growth inhibition and decreased cell cycle proteins. Finally, in vivo WEGS treatment significantly inhibited the growth of HCT116 tumor cell xenografts in nude mice with no negative side effects, including loss of body weight. These results describe the molecular mechanisms whereby the WEGS might inhibit proliferation of colon cancer both in vitro and in vivo, suggesting that WEGS has potential as an anticancer agent for the treatment of malignancies.
中国和韩国将皂荚刺作为药用植物。然而，皂荚刺水提物（WEGS）抗肿瘤作用的机制尚不清楚。用 800μg/ml（IC₅₀）的 WEGS 处理 HCT116 细胞，细胞生长明显减少，细胞周期停滞在 G2/M 期。G2/M 期阻滞与 p53 水平升高和检验点蛋白 cyclinB1、Cdc2 和 Cdc25c 下调有关。此外，WEGS 处理诱导细胞外信号调节激酶（ERK）、p38 MAP 激酶和 JNK（c-Jun N-末端激酶）磷酸化。此外，用 ERK 特异性抑制剂 PD98059 处理细胞可阻断 WEGS 介导的 p53 表达，从而抑制 ERK。同样，在 WEGS 处理的细胞中阻断 ERK 功能可逆转细胞生长抑制和细胞周期蛋白减少。最后，WEGS 体内处理显著抑制裸鼠中 HCT116 肿瘤细胞异种移植物的生长，无体重减轻等负面副作用。这些结果描述了 WEGS 可能在体外和体内抑制结肠癌增殖的分子机制，表明 WEGS 有作为治疗恶性肿瘤的抗癌剂的潜力。
