Anticancer potential of Amaryllidaceae alkaloids evaluated by screening with a panel of human cells, real-time cellular analysis and Ehrlich tumor-bearing mice
Anticancer potential of Amaryllidaceae alkaloids evaluated by screening with a panel of human cells, real-time cellular analysis and Ehrlich tumor-bearing mice
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DOI：
10.1016/j.cbi.2017.07.018
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发表时间：
2017-09-25
影响因子：
5.1
通讯作者：
Rezacova, Martina
中科院分区：
文献类型：
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作者：
Havelek, Radim;Muthna, Darina;Rezacova, Martina
在这项研究中，筛选了 22 种石蒜科生物碱的抗癌潜力。使用 WST-1 测定评估所有分离株对不同组织来源的 17 种人类细胞类型的抗增殖活性。此外，我们还利用实时细胞分析 xCELLigence 系统确定了抗增殖作用。此后，为了评估最有效的分子血红素鲜为人知的体内抗癌潜力，使用艾利希肿瘤小鼠模型进行了初步研究。结果表明，血红胺、石蒜碱和血红素具有最高的抗增殖活性。单剂量10μM处理后的平均生长百分比(GP)值是未处理的对照细胞(100％)的血红胺21％、石蒜碱21％和血红素27％。此外，haemanthamine、lycorine 和 haemanthidine 对所有测试的细胞系均表现出显着的细胞毒性，各个 IC50 值在微摩尔范围内。 xCELLigence 对阻抗的动态实时测量表明，这三种化合物在以 10 mM 或更高浓度处理 10 小时后抑制细胞增殖。遗憾的是，在后续的体内抗肿瘤活性研究中，血红素没有显示出统计上显着的肿瘤大小减小，并且没有延长艾利希肿瘤小鼠的生存时间。综上所述，这些结果为石蒜科生物碱作为抗癌药物的开发提供了新的线索和指导。 (C) 2017 Elsevier B.V. 保留所有权利。
In this study, twenty-two Amaryllidaceae alkaloids were screened for their anticancer potential. All isolates were evaluated for antiproliferative activities on a panel of 17 human cell types of different tissue origin using WST-1 assay. In addition, we determined the antiproliferative effect with a real-time cell analysis xCELLigence system. Thereafter, to evaluate the barely known in vivo anticancer potential of the most potent molecule haemanthamine, a preliminary study was performed using an Ehrlich tumor-bearing mice model. The results showed that haemanthamine, lycorine and haemanthidine exerted the highest antiproliferative activity. The mean growth percent (GP) value after a single-dose 10 mu M treatment was for haemanthamine 21%, for lycorine 21% and for haemanthidine 27% that of untreated control cells (100%). Furthermore, haemanthamine, lycorine and haemanthidine exhibited significant cytotoxicities against all the tested cell lines with individual IC50 values in the micromolar range. Dynamic real-time measures of impedance by xCELLigence indicated that these three compounds suppress cell proliferation after 10 h of treatment at a concentration of 10 mM or higher. Regrettably, in a follow-up in vivo antitumor activity study, haemanthamine showed no statistically significant reduction in the tumor size with no prolongation of survival time of Ehrlich tumor-bearing mice. Taken together, these results provide a new clue and guidance for exploiting Amaryllidaceae alkaloids as anticancer agents. (C) 2017 Elsevier B.V. All rights reserved.