Fan Jingzhang, Yang Xin, Bi Zhenggang
Department of Orthopaedic Surgery, First Affiliated Hospital of Harbin Medicine University, 23 Youzheng Street, Nangang District, Harbin, China.
Tumour Biol. 2015 Feb;36(2):1135-41. doi: 10.1007/s13277-014-2723-1. Epub 2014 Oct 21.
6-Gingerol, a major component of ginger, is demonstrated to possess a variety of pharmacological activities. Despite demonstration of its anti-cancer activity, the exact mechanism underlying the effects of 6-gingerol against sarcoma remains sketchy. In the present study, we investigated the anti-cancer effects of 6-gingerol on osteosarcoma cells. MTT assay was performed to determine cell viability. Phosphorylation and protein levels were determined by immunoblotting. Cell cycle was determined using flow cytometry. Quantitative polymerase chain reaction was employed to determine the changes in the messenger RNA (mRNA) expression of genes. Treatment with 6-gingerol resulted in a significant decrease in the viability of osteosarcoma cells in a dose-dependent fashion. In parallel, the number of cells arrested at the sub-G1 cell cycle phase was significantly increased. The results showed that 6-gingerol induced activation of caspase cascades and regulated cellular levels of Bcl2 and Bax. Moreover, 6-gingerol activated AMP-activated protein kinase (AMPK) signaling associated with the apoptotic pathways. Our findings suggest that 6-gingerol suppresses the growth of osteosarcoma cells. The anti-cancer activity is attributed to the activation of apoptotic signaling and the inhibition of anti-apoptotic signaling incorporating with 6-gingerol-induced AMPK activation. The study identifies a new molecular mechanism by which AMPK is involved in anti-cancer effects of 6-gingerol.
6-姜酚是生姜的主要成分,已被证明具有多种药理活性。尽管已证实其具有抗癌活性,但6-姜酚抗肉瘤作用的确切机制仍不明确。在本研究中,我们调查了6-姜酚对骨肉瘤细胞的抗癌作用。采用MTT法测定细胞活力。通过免疫印迹法测定磷酸化和蛋白质水平。使用流式细胞术测定细胞周期。采用定量聚合酶链反应来确定基因信使核糖核酸(mRNA)表达的变化。用6-姜酚处理导致骨肉瘤细胞活力以剂量依赖性方式显著降低。同时,停滞在亚G1细胞周期阶段的细胞数量显著增加。结果表明,6-姜酚诱导半胱天冬酶级联反应的激活并调节Bcl2和Bax的细胞水平。此外,6-姜酚激活了与凋亡途径相关的AMP激活蛋白激酶(AMPK)信号传导。我们的研究结果表明,6-姜酚抑制骨肉瘤细胞的生长。其抗癌活性归因于凋亡信号的激活以及与6-姜酚诱导的AMPK激活相结合的抗凋亡信号的抑制。该研究确定了一种新的分子机制,即AMPK参与6-姜酚的抗癌作用。