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从巴西东北海岸采集的沉积物中分离得到的一株假交替单胞菌的次生代谢产物研究。

Studies on the secondary metabolites of a Pseudoalteromonas sp. isolated from sediments collected at the northeastern coast of Brazil.

机构信息

Instituto de Ciências do Mar, LABOMAR, Universidade Federal do Ceará, Fortaleza, CE, Brasil.

出版信息

Chem Biodivers. 2012 Feb;9(2):418-27. doi: 10.1002/cbdv.201100092.

DOI:10.1002/cbdv.201100092
PMID:22344918
Abstract

Continuing search for anticancer compounds from the marine environment, we have studied microorganisms that inhabit intertidal sediments of the northeastern Brazilian coast. Of the 32 strains isolated, 13 were selected for biological evaluation of their crude extracts. The acetate extract obtained from a Gram-negative bacterium was strongly active against cancer cell lines with IC(50) values that ranged from 0.04 (HL60 leukemia cells) to 0.26 μg/ml (MDA MB-435 melanoma cells). The bacterium was identified as a Pseudoalteromonas sp. based on 16S rRNA gene sequencing. A bioassay-guided fractionation of the active extract led to the isolation of prodigiosin, a well-known tripyrrole red pigment with immunosuppressive and anticancer activities. Further experiments with ErbB-2 overexpressing cell lines, including HB4a-C3.6 (moderate overexpression), HB4a-C5.2 (high overexpression), and the parental HB4a cell line, were performed. Prodigiosin was moderately active toward HB4a cells with an IC(50) of 4.6 μg/ml, while it was 115 and 18 times more active toward HB4a-C3.6 cells (IC(50) of 0.04 μg/ml) and HB4a-C5.2 (IC(50) of 0.26 μg/ml) cells, respectively. These data suggest that, in spite of its previously described apoptosis-inducing properties, prodigiosin can selectively recognize cells overexpressing ErbB-2, which could be highly appealing in human breast cancer therapy.

摘要

为了继续从海洋环境中寻找抗癌化合物,我们研究了栖息在巴西东北部沿海潮间带沉积物中的微生物。在所分离的 32 株菌中,选择了 13 株进行粗提物的生物评价。从革兰氏阴性菌获得的乙酸乙酯提取物对癌细胞系具有很强的活性,IC 50 值范围为 0.04(HL60 白血病细胞)至 0.26μg/ml(MDA-MB-435 黑色素瘤细胞)。根据 16S rRNA 基因测序,该细菌被鉴定为假交替单胞菌属。活性提取物的生物测定指导分离导致了灵菌红素的分离,灵菌红素是一种众所周知的三吡咯红色色素,具有免疫抑制和抗癌活性。进一步用 ErbB-2 过表达细胞系(包括 HB4a-C3.6(中度过表达)、HB4a-C5.2(高度过表达)和亲本 HB4a 细胞系)进行了实验。灵菌红素对 HB4a 细胞具有中度活性,IC 50 为 4.6μg/ml,而对 HB4a-C3.6 细胞(IC 50 为 0.04μg/ml)和 HB4a-C5.2 细胞(IC 50 为 0.26μg/ml)的活性分别提高了 115 倍和 18 倍。这些数据表明,尽管灵菌红素具有先前描述的诱导细胞凋亡的特性,但它可以选择性地识别过表达 ErbB-2 的细胞,这在人类乳腺癌治疗中可能非常有吸引力。

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