Gao Zhenbei, Kang Xiao, Hu Jun, Ju Yong, Xu Chuanlian
The Laboratory of Proteomics and Molecular Enzymology, College of Life Science, Zhejiang Sci-Tech University, Xiasha Higher Education Zone, Hangzhou, 310018, Zhejiang Province, China.
Cytotechnology. 2012 Aug;64(4):421-8. doi: 10.1007/s10616-011-9419-9. Epub 2012 Jan 25.
Glycyrrhetinic acid (GA) is the active compound in Glycyrrhizae radix, a famous traditional Chinese medicine. Recently the anticancer activity of GA became the focus of scientific interest and many GA derivatives were developed as anti-tumor lead compounds. We previously reported that AEGA, a GA derivative, has proliferation inhibition and apoptosis-inducing activity in various human tumor cells. The present study was undertaken to further investigate the molecular mechanisms involved in AEGA-induced apoptosis in human leukemia K562 cells. AEGA can inhibit the growth of K562 cells in dose- and time-dependent manners determined by the MTT assay. Induction of apoptosis was evidenced by morphological changes and biochemical markers such as cell shrinkage, chromatin condensation and DNA ladder formation. Further mechanistic analysis revealed that AEGA induced apoptosis through the collapse of mitochondrial membrane potential, the accumulation of the cytosolic cytochrome c and the activation of caspase-9 and caspase-3. The apoptosis induction by AEGA was associated with the alteration in the ratio of Bcl-2/Bax protein expression. These results suggest that AEGA may induce apoptosis through a mitochondria-mediated pathway, and might have the therapeutic value against hematological malignancies.
甘草次酸（GA）是著名的传统中药甘草的活性成分。最近，GA的抗癌活性成为科学研究的热点，许多GA衍生物被开发为抗肿瘤先导化合物。我们之前报道过，GA衍生物AEGA在多种人类肿瘤细胞中具有增殖抑制和诱导凋亡的活性。本研究旨在进一步探讨AEGA诱导人类白血病K562细胞凋亡的分子机制。通过MTT法测定，AEGA能以剂量和时间依赖性方式抑制K562细胞的生长。细胞形态变化以及细胞皱缩、染色质浓缩和DNA梯状条带形成等生化标志物证实了凋亡的诱导。进一步的机制分析表明，AEGA通过线粒体膜电位的崩溃、胞质细胞色素c的积累以及caspase-9和caspase-3的激活诱导凋亡。AEGA诱导的凋亡与Bcl-2/Bax蛋白表达比例的改变有关。这些结果表明，AEGA可能通过线粒体介导的途径诱导凋亡，并且可能对血液系统恶性肿瘤具有治疗价值。
