Synergistic property of cordycepin in cultivated Cordyceps militaris-mediated apoptosis in human leukemia cells

Synergistic property of cordycepin in cultivated Cordyceps militaris-mediated apoptosis in human leukemia cells
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DOI:
10.1016/j.phymed.2014.07.014
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发表时间:
2014-10-15
期刊:
影响因子:
7.9
通讯作者:
Shen, Tang-Long
Shen, Tang-Long
中科院分区:
医学1区
文献类型:
--
作者:
Chou, Shang-Min;Lai, Wan-Jung;Shen, Tang-Long

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蛹虫草是一种著名的中国传统药用蘑菇,经常用于滋补,最近对癌症干预有潜在的兴趣。本实验研究了军伞菌培养菌丝(CMmy)和培养子实体(CMFB)热水提取物对癌细胞的杀伤活性。我们发现CMFB比CMmy对各种癌细胞表现出更大的细胞毒作用。CMFB可诱导人HL-60白血病细胞的凋亡表型,包括凋亡小体的形成、DNA阶梯、caspase 3的激活和PARP蛋白的裂解,但相同浓度的CMmy仅能轻微诱导。CMFB中虫草素含量(10.47 mg/g)显著高于CMmy (0.69 mg/g)(-15.2倍)。利用等密度分析,观察了CMmy和虫草素在不同组合浓度下的细胞毒性协同作用。通过将虫草素补充到CMmy中达到与CMFB相当的水平,我们观察到CMmy (500 vg/m1)与虫草素(4.8 tig/m1)诱导的细胞凋亡水平与CMFB (500 vg/m1)相似。综上所述,我们的研究结果表明,虫草素具有协同细胞毒作用,可抑制军性虫草介导的人白血病细胞凋亡,因此可以解释CMFB比CMmy具有更好的抗增殖活性。(C) 2014 Elsevier GmbH版权所有。
Cordyceps militaris is a well-known Chinese traditional medicinal mushroom frequently used for tonics and recently of a potential interest for cancer intervention. Here, we explored the cancer cell killing activity of the hot water extracts of C. militaris cultured mycelia (CMmy) and cultivated fruiting bodies (CMFB). We found that CMFB exhibited a greater cytotoxic effect against various cancer cells over CMmy. Apoptotic phenotypes including apoptotic body formation, DNA laddering, caspase 3 activation and cleavage of PARP proteins were induced by CMFB treatment but only slightly induced by same concentration of CMmy treatment in human HL-60 leukemia cells. Cordycepin in CMFB (10.47 mg/g) is significantly higher (-15.2 times) than that of CMmy (0.69 mg/g). Using isobolographic analysis, the synergy of cytotoxicity was observed across different combined concentrations of CMmy and cordycepin. By complementing cordycepin into CMmy to the level comparable with CMFB, we observed that CMmy (500 vg/m1) with cordycepin (4.8 tig/m1) induced apoptosis to a level similar to that induced by CMFB (500 vg/m1). Together, our results suggest that cordycepin possesses a synergistic cytotoxic effect with Cordyceps militaris-mediated apoptosis in human leukemia cells and therefore explaining a better anti-proliferating activity of CMFB over CMmy. (C) 2014 Elsevier GmbH. All rights reserved.