Huang Lan-Zhen, Wang Juan, Lu Fei-Ting, Yang Fei-Cheng, Chen Xu, Hong Xue, Jiang Xiao-Shan
Center for Science Research, Guilin Medical University, Guilin 541004, China.
Zhongguo Zhong Yao Za Zhi. 2013 Jun;38(11):1812-5.
To investigate the anti-proliferative effects of curcumol, an herbal extract from curcuma, in human hepatocarcinoma HepG2 cells, and its possible molecular mechanism.
The effects of curcumol on human hepatocarcinoma cells were assessed in vitro. Proliferation of HepG2 cells treated with various concentration (2.5-10 mg x L(-1)) of curcumol was determined using the MTT assay and the distribution of cell cycle of HepG2 cells was analyzed using the FCM technique. Expression of 14 cell cycle regulation-related genes were assessed by TaqMan real-time polymerase chain reaction (RT-PCR) method and Western blot.
Curcumol significantly inhibited the proliferation of HepG2 cells and induced G1 phase arrest in a dose- and time-dependent manner. The mRNA levels of pRB1, cyclin D1, CDK2, CDK8 and p27KIP1 were elevated, while cyclin A1 decreased, in both of the low (25 mg x L(-1)) and the high dose (100 mg x L(-1)) treatment of curcumol. There were no significant changes in the expression of either cyclin E1 or CDK4. The expression of p53 and its target genes p21WAF1 and Wip1 protein were increased.
Curcumol can inhibit the proliferation of HepG2 cells in vitro and induce G1 arrest of cell cycle through mechanisms activating p53 and pRB pathways that involve genes of cyclin A1, CDK2, CDK8, p21WAF1 and p27KIP1.
研究莪术提取物莪术醇对人肝癌HepG2细胞的抗增殖作用及其可能的分子机制。
体外评估莪术醇对人肝癌细胞的作用。采用MTT法测定不同浓度(2.5 - 10 mg·L⁻¹)莪术醇处理的HepG2细胞的增殖情况,并使用流式细胞术(FCM)分析HepG2细胞的细胞周期分布。通过TaqMan实时聚合酶链反应(RT-PCR)法和蛋白质免疫印迹法评估14种细胞周期调控相关基因的表达。
莪术醇以剂量和时间依赖性方式显著抑制HepG2细胞的增殖并诱导G1期阻滞。在低剂量(25 mg·L⁻¹)和高剂量(100 mg·L⁻¹)莪术醇处理中,pRB1、细胞周期蛋白D1、细胞周期蛋白依赖性激酶2(CDK2)、CDK8和p27KIP1的mRNA水平升高,而细胞周期蛋白A1降低。细胞周期蛋白E1或CDK4的表达无显著变化。p53及其靶基因p21WAF1和Wip1蛋白的表达增加。
莪术醇可在体外抑制HepG2细胞的增殖,并通过激活涉及细胞周期蛋白A1、CDK2、CDK8、p21WAF1和p27KIP1基因的p53和pRB途径诱导细胞周期的G1期阻滞。