Division of Hepatology and Gastroenterology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
Evid Based Complement Alternat Med. 2012;2012:326096. doi: 10.1155/2012/326096. Epub 2012 Jun 7.
6-Gingerol, a natural component of ginger, has been widely reported to possess antiinflammatory and antitumorigenic activities. Despite its potential efficacy against cancer, the anti-tumor mechanisms of 6-gingerol are complicated and remain sketchy. In the present study, we aimed to investigate the anti-tumor effects of 6-gingerol on colon cancer cells. Our results revealed that 6-gingerol treatment significantly reduced the cell viability of human colon cancer cell, LoVo, in a dose-dependent manner. Further flow cytometric analysis showed that 6-gingerol induced significant G2/M phase arrest and had slight influence on sub-G1 phase in LoVo cells. Therefore, levels of cyclins, cyclin-dependent kinases (CDKs), and their regulatory proteins involved in S-G2/M transition were investigated. Our findings revealed that levels of cyclin A, cyclin B1, and CDK1 were diminished; in contrast, levels of the negative cell cycle regulators p27(Kip1) and p21(Cip1) were increased in response to 6-gingerol treatment. In addition, 6-gingerol treatment elevated intracellular reactive oxygen species (ROS) and phosphorylation level of p53. These findings indicate that exposure of 6-gingerol may induce intracellular ROS and upregulate p53, p27(Kip1), and p21(Cip1) levels leading to consequent decrease of CDK1, cyclin A, and cyclin B1 as result of cell cycle arrest in LoVo cells. It would be suggested that 6-gingerol should be beneficial to treatment of colon cancer.
6-姜酚是生姜中的一种天然成分,已被广泛报道具有抗炎和抗肿瘤作用。尽管它对癌症有潜在的疗效,但 6-姜酚的抗肿瘤机制很复杂,目前仍不清楚。在本研究中,我们旨在研究 6-姜酚对结肠癌细胞的抗肿瘤作用。我们的结果表明,6-姜酚处理以剂量依赖的方式显著降低人结肠癌细胞 LoVo 的细胞活力。进一步的流式细胞术分析表明,6-姜酚诱导 LoVo 细胞中显著的 G2/M 期阻滞,对 sub-G1 期影响较小。因此,研究了参与 S-G2/M 期转换的细胞周期蛋白、细胞周期蛋白依赖性激酶(CDKs)及其调节蛋白的水平。我们的研究结果表明,cyclin A、cyclin B1 和 CDK1 的水平降低;相反,p27(Kip1)和 p21(Cip1)的水平增加。此外,6-姜酚处理增加了细胞内活性氧(ROS)和 p53 的磷酸化水平。这些发现表明,6-姜酚的暴露可能会诱导细胞内 ROS 并上调 p53、p27(Kip1)和 p21(Cip1)的水平,导致 CDK1、cyclin A 和 cyclin B1 的减少,从而导致 LoVo 细胞周期阻滞。这表明 6-姜酚可能有益于结肠癌的治疗。