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水黄皮属植物制剂及其主要成分与蓖麻毒素和白屈菜红碱对人癌细胞的抗增殖潜力比较。

Antiproliferative potential from aqueous Viscum album L. preparations and their main constituents in comparison with ricin and purothionin on human cancer cells.

机构信息

WALA Heilmittel GmbH, Dorfstr. 1, 73087, Bad Boll/Eckwälden, Germany.

WALA Heilmittel GmbH, Dorfstr. 1, 73087, Bad Boll/Eckwälden, Germany.

出版信息

J Ethnopharmacol. 2019 May 23;236:100-107. doi: 10.1016/j.jep.2019.02.047. Epub 2019 Mar 3.

DOI:10.1016/j.jep.2019.02.047
PMID:30840914
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Mistletoe has been used since ancient times in Europe mostly for medicinal purposes. Since 1917, mistletoe preparations have been applied in cancer therapy and today are the most frequently used complementary medicine in tumor treatment. The main cytotoxic constituents of Viscum album are lectins and viscotoxins.

AIM OF THE STUDY

The aim of this in vitro study was to investigate the antiproliferative potential of Viscum album preparations from different host trees and to assess the impact of mistletoe lectin 1 (ML-1) and viscotoxin A (VT-A) in comparison to a structurally similar lectin and thionin.

MATERIALS AND METHODS

By means of widely accepted 2D Alamar Blue Assay, based on population counting of living cells using a fluorescent cell viability dye, the potential impact to inhibit tumor cell of the mistletoe preparations (Iscucin) and their single compounds (ML-1 and VT-A) on the cell growth of six human cancer cell lines were evaluated. Also the mixture of ML-1 and VT-A corresponding to the contents in the specific mistletoe preparations were monitored. Ricin and purothionin were used as reference lectin and reference thionin, respectively.

RESULTS

The lung carcinoma cell line HCC827 was very sensitive to the Iscucin preparations. Very strong antiproliferative effects were found with IscucinSalicis and Tiliae and a strong with IscucinCrataegi, Mali and Populi. The IC concentrations of the Iscucin preparations correlated with their respective ML-1 contents, but the ML-1 levels were much lower than the IC concentration of isolated ML-1 (1 ng/ml - 56 ng/ml). ML-1 was much more effective than ricin. Iscucin preparations, ML-1 and ricin showed antiproliferative activity on human tumor cells. VT-A and purothionin had no effect on cell viability in the concentration ranges tested.

CONCLUSION

The complete mistletoe extract is more potent to inhibit tumor cell proliferation than isolated ML-1 at an equivalent concentration level. Phenolic compounds found in all Iscucin preparations might contribute to uphold the cytotoxic activity of ML-1 by antioxidative action. However, further studies are necessary to evaluate the role of VT-A and possible synergistic actions to the antiproliferative effect of aqueous mistletoe extracts.

摘要

民族药理学相关性

自古以来,欧洲人就一直将槲寄生用于医疗用途。自 1917 年以来,槲寄生制剂已应用于癌症治疗,如今已成为肿瘤治疗中最常用的补充药物。欧洲槲寄生的主要细胞毒素成分为凝集素和粘毒素。

研究目的

本体外研究旨在调查来自不同宿主树的欧洲槲寄生制剂的抗增殖潜力,并评估其与结构相似的凝集素和硫肽相比,槲寄生凝集素 1(ML-1)和粘毒素 A(VT-A)的影响。

材料和方法

通过广泛接受的二维 Alamar Blue 测定法,基于使用荧光细胞活力染料对活细胞进行群体计数,评估了槲寄生制剂(Iscucin)及其单一化合物(ML-1 和 VT-A)对六种人癌细胞系的肿瘤细胞生长的潜在抑制作用。还监测了与特定槲寄生制剂中含量相对应的 ML-1 和 VT-A 混合物。蓖麻毒素和普洛托菌素分别用作参考凝集素和参考硫肽。

结果

肺腺癌细胞系 HCC827 对 Iscucin 制剂非常敏感。IscucinSalicis 和 Tiliae 具有很强的抗增殖作用,IscucinCrataegi、Mali 和 Populi 具有很强的抗增殖作用。Iscucin 制剂的 IC 浓度与各自的 ML-1 含量相关,但 ML-1 水平远低于分离 ML-1 的 IC 浓度(1ng/ml-56ng/ml)。ML-1 比蓖麻毒素更有效。Iscucin 制剂、ML-1 和蓖麻毒素对人肿瘤细胞具有抗增殖活性。在测试的浓度范围内,VT-A 和普洛托菌素对细胞活力没有影响。

结论

在等效浓度水平下,完整的槲寄生提取物比分离的 ML-1 更能抑制肿瘤细胞增殖。所有 Iscucin 制剂中发现的酚类化合物可能通过抗氧化作用有助于维持 ML-1 的细胞毒性活性。然而,仍需要进一步研究来评估 VT-A 的作用以及对水槲寄生提取物抗增殖作用的可能协同作用。

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