Senthil V, Ramadevi S, Venkatakrishnan V, Giridharan P, Lakshmi B S, Vishwakarma R A, Balakrishnan A
Centre For Biotechnology, Anna University, Chennai 600025, Tamil Nadu, India.
Chem Biol Interact. 2007 Apr 5;167(1):19-30. doi: 10.1016/j.cbi.2007.01.004. Epub 2007 Jan 12.
The present study is on the growth inhibitory effect of Withania somnifera methanolic leaf extract and its active component, withanolide on HL-60 promyelocytic leukemia cells. The decrease in survival rate of HL-60 cells was noted to be associated with a time dependent decrease in the Bcl-2/Bax ratio, leading to up regulation of Bax. Both the crude leaf extract and the active component activated the apoptotic cascade through the cytochrome c release from mitochondria. The activation of caspase 9, caspase 8 and caspase 3 revealed that caspase was a key mediator in the apoptotic pathway. DNA fragmentation analysis revealed typical ladders as early as 12h indicative of caspase 3 role in the apoptotic pathway. Flow cytometry data demonstrated an increase of sub-G1 peak upon treatment by 51% at 24h, suggesting the induction of apoptotic cell death in HL-60 cells.
本研究旨在探讨睡茄甲醇叶提取物及其活性成分睡茄内酯对HL-60早幼粒细胞白血病细胞的生长抑制作用。研究发现，HL-60细胞存活率的降低与Bcl-2/Bax比值随时间的下降有关，从而导致Bax上调。粗叶提取物和活性成分均通过线粒体释放细胞色素c激活凋亡级联反应。半胱天冬酶9、半胱天冬酶8和半胱天冬酶3的激活表明，半胱天冬酶是凋亡途径中的关键介质。DNA片段化分析显示，早在12小时就出现了典型的梯状条带，表明半胱天冬酶3在凋亡途径中发挥作用。流式细胞术数据表明，处理24小时后，亚G1峰增加了51%，提示HL-60细胞发生了凋亡性细胞死亡。
