Apoptosis induction in HL-60 cells and inhibition of topoisomerase II by triterpene celastrol
Apoptosis induction in HL-60 cells and inhibition of topoisomerase II by triterpene celastrol
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DOI：
10.1271/bbb.67.1883
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发表时间：
2003-09-01
影响因子：
1.6
通讯作者：
Sakato, N
中科院分区：
文献类型：
--
作者：
Nagase, M;Oto, J;Sakato, N
南蛇藤酚是从卫矛科植物中提取的一种三萜类化合物，具有抗癌和抗炎活性。在本研究中，我们研究雷公藤红素是否可以诱导人白血病HL-60模型系统中的细胞凋亡。发现雷公藤红素诱导细胞凋亡，并且发现雷公藤红素及其衍生物诱导核小体间DNA片段化的效力的等级顺序为雷公藤红素> cela-H，远大于其他衍生物=媒介物对照。已知许多抗癌药物具有抑制拓扑异构酶II的能力，因此雷公藤红素及其衍生物对拓扑异构酶II的抑制活性也被探索。发现抑制活性的等级顺序为雷公藤红素>依托泊苷>cela-H，表明cela衍生物的促凋亡活性对应于其对拓扑异构酶II的抑制活性。这些数据表明雷公藤红素可能通过细胞凋亡机制沿着拓扑异构酶II抑制作用产生其抗癌活性等作用。
Celastrol, which is a triterpene purified from Celastraceae plants, has anticancer and anti-inflammatory activities. In this study we investigated to clarify whether celastrol can induce apoptosis in a human leukemia HL-60 model system. Celastrol was found to induce apoptosis, and the rank order of the potency of celastrol and its derivatives to induce internucleosomal DNA fragmentation was found to be celastrol > cela-H much greater than the other derivatives = vehicle control. Many anticancer agents are known to possess the ability to inhibit topoisomerase II, so the inhibitory activities of celastrol and its derivatives on topoisomerase II were also explored. The rank order of the inhibitory activity was found to be celastrol>etoposide>cela-H, indicating that the apoptosis-inducing activities of cela derivatives correspond to their inhibitory activities on topoisomerase II. These data suggested that celastrol may cause its effects such as anticancer activity by the mechanism of apoptosis along with topoisomerase II inhibition.