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泽泻醇A:一种从拟茎点霉属真菌中提取的具有选择性细胞毒性的蒽醌类化合物

Altersolanol A: a selective cytotoxic anthraquinone from a Phomopsis sp.

作者信息

Mishra P D, Verekar S A, Deshmukh S K, Joshi K S, Fiebig H H, Kelter G

机构信息

Piramal Enterprises Limited, Goregaon (East), Mumbai, India.

出版信息

Lett Appl Microbiol. 2015 Apr;60(4):387-91. doi: 10.1111/lam.12384. Epub 2015 Feb 8.

DOI:10.1111/lam.12384
PMID:25534717
Abstract

UNLABELLED

The cytotoxic compound Altersolanol A, an anthraquinone derivative was isolated from PM0409092 a fungus of Nyctanthes arbor-tristis (family Oleaceae). It was identified as a Phomopsis sp. by DNA amplification and sequencing of the ITS region. The chemical structure of Altersolanol A was elucidated from its physicochemical properties, 2D NMR spectroscopy and other spectroscopic data. The compound has in vitro cytotoxic activity against 34 human cancer cell lines with mean IC50 (IC70) values of 0.005 μg ml(-1) (0.024 μg ml(-1)) respectively. Altersolanol A, a kinase inhibitor, induces cell death by apoptosis through the cleavage by Caspase-3 and -9 and by decreased anti-apoptotic protein expression. There are several previous reports of the anticancer activity of Altersolanol A, but we report here an extensive study using 36 cell lines which gives wider spectrum of results.

SIGNIFICANCE AND IMPACT OF THE STUDY

This study confirms the cytotoxic potential of Altersolanol A isolated from the endophyte Phomopsis sp. (PM0409092) of the plant Nyctanthes arbor-tristis. The compound exhibits in vitro cytotoxicity against 34 human cancer cell lines with mean IC50 (IC70) value of 0.005 μg ml(-1) (0.024 μg ml(-1)). This is an in-depth report of Altersolanol A against a panel of 34 human cancer cell lines and extends observations from previous studies indicating that Altersolanol A can be used for the development of chemotherapeutics. Altersolanol A, a kinase inhibitor, induces cell death by apoptosis through the cleavage of Caspase-3 and -9 and by decreased anti-apoptotic protein expression.

摘要

未标记

细胞毒性化合物Altersolanol A,一种蒽醌衍生物,是从夜花树(木犀科)的真菌PM0409092中分离出来的。通过对ITS区域进行DNA扩增和测序,它被鉴定为拟茎点霉属真菌。Altersolanol A的化学结构通过其物理化学性质、二维核磁共振光谱和其他光谱数据得以阐明。该化合物对34种人类癌细胞系具有体外细胞毒性活性,平均IC50(IC70)值分别为0.005 μg/ml(0.024 μg/ml)。Altersolanol A作为一种激酶抑制剂,通过Caspase-3和-9的切割以及抗凋亡蛋白表达的降低,诱导细胞凋亡而导致细胞死亡。之前有几篇关于Altersolanol A抗癌活性 的报道,但我们在此报告一项使用36种细胞系的广泛研究,其给出了更广泛的结果。

研究的意义和影响

本研究证实了从夜花树的内生拟茎点霉属真菌(PM0409092)中分离出的Altersolanol A的细胞毒性潜力。该化合物对34种人类癌细胞系表现出体外细胞毒性,平均IC50(IC70)值为0.005 μg/ml(0.024 μg/ml)。这是关于Altersolanol A对一组34种人类癌细胞系的深入报告,并扩展了先前研究的观察结果,表明Altersolanol A可用于化疗药物的开发。Altersolanol A作为一种激酶抑制剂,通过Caspase-3和-9的切割以及抗凋亡蛋白表达的降低,诱导细胞凋亡而导致细胞死亡。

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