Elkady Ayman I, Abu-Zinadah Osama A, Hussein Rania Abd El Hamid
Oncol Res. 2017 Jul 5;25(6):897-912. doi: 10.3727/096504016X14816352324532. Epub 2016 Dec 21.
There is an urgent need to improve the clinical management of hepatocellular carcinoma (HCC), one of the most common causes of global cancer-related deaths. Zingibar officinale is a medicinal herb used throughout history for both culinary and medicinal purposes. It has antioxidant, anticarcinogenic, and free radical scavenging properties. Previously, we proved that the crude flavonoid extract of Z. officinale (CFEZO) inhibited growth and induced apoptosis in several cancer cell lines. However, the effect of the CFEZO on an HCC cell line has not yet been evaluated. In this study, we explored the anticancer activity of CFEZO against an HCC cell line, HepG2. CFEZO significantly inhibited proliferation and induced apoptosis in HepG2 cells. Typical apoptotic morphological and biochemical changes, including cell shrinkage and detachment, nuclear condensation and fragmentation, DNA degradation, and comet tail formation, were observed after treatments with CFEZO. The apoptogenic activity of CFEZO involved induction of ROS, depletion of GSH, disruption of the mitochondrial membrane potential, activation of caspase 3/9, and an increase in the Bax/Bcl-2 ratio. CFEZO treatments induced upregulation of p53 and p21 expression and downregulation of cyclin D1 and cyclin-dependent kinase-4 expression, which were accompanied by G2/M phase arrest. These findings suggest that CFEZO provides a useful foundation for studying and developing novel chemotherapeutic agents for the treatment of HCC.
迫切需要改善肝细胞癌(HCC)的临床管理,HCC是全球癌症相关死亡的最常见原因之一。姜是一种历史悠久的药草,兼具烹饪和药用价值。它具有抗氧化、抗癌和清除自由基的特性。此前,我们证明了姜的粗黄酮提取物(CFEZO)在几种癌细胞系中具有抑制生长和诱导凋亡的作用。然而,CFEZO对肝癌细胞系的作用尚未得到评估。在本研究中,我们探究了CFEZO对肝癌细胞系HepG2的抗癌活性。CFEZO显著抑制了HepG2细胞的增殖并诱导其凋亡。在用CFEZO处理后,观察到了典型的凋亡形态学和生化变化,包括细胞皱缩和脱落、核浓缩和碎片化、DNA降解以及彗星尾形成。CFEZO的凋亡诱导活性涉及活性氧的诱导、谷胱甘肽的消耗、线粒体膜电位的破坏、半胱天冬酶3/9的激活以及Bax/Bcl-2比值的增加。CFEZO处理诱导了p53和p21表达的上调以及细胞周期蛋白D1和细胞周期蛋白依赖性激酶4表达的下调,同时伴有G2/M期阻滞。这些发现表明,CFEZO为研究和开发用于治疗肝癌的新型化疗药物提供了有用基础。