Department of Biomedicine, University of Bergen, Jonas Lies Vei 91, 5009 Bergen, Norway.
J Ind Microbiol Biotechnol. 2011 Apr;38(4):489-501. doi: 10.1007/s10295-010-0791-9. Epub 2010 Aug 6.
Cyanobacteria (83 strains and seven natural populations) were screened for content of apoptosis (cell death)-inducing activity towards neoplastic cells of the immune (jurkat acute T-cell lymphoma) and hematopoetic (acute myelogenic leukemia) lineage. Apoptogenic activity was frequent, even in strains cultured for decades, and was unrelated to whether the cyanobacteria had been collected from polar, temperate, or tropic environments. The activity was more abundant in the genera Anabaena and Microcystis compared to Nostoc, Phormidium, Planktothrix, and Pseudanabaena. Whereas the T-cell lymphoma apoptogens were frequent in organic extracts, the cell death-inducing activity towards leukemia cells resided mainly in aqueous extracts. The cyanobacteria were from a culture collection established for public health purposes to detect toxic cyanobacterial blooms, and 54 of them were tested for toxicity by the mouse bioassay. We found no correlation between the apoptogenic activity in the cyanobacterial isolates with their content of microcystin, nor with their ability to elicit a positive standard mouse bioassay. Several strains produced more than one apoptogen, differing in biophysical or biological activity. In fact, two strains contained microcystin in addition to one apoptogen specific for the AML cells, and one apoptogen specific for the T-cell lymphoma. This study shows the potential of cyanobacterial culture collections as libraries for bioactive compounds, since strains kept in cultures for decades produced apoptogens unrelated to the mouse bioassay detectable bloom-associated toxins.
蓝藻(83 株和 7 个自然种群)被筛选出具有诱导免疫(jurkat 急性 T 细胞淋巴瘤)和造血(急性髓系白血病)谱系肿瘤细胞凋亡(细胞死亡)的活性。即使在培养了几十年的菌株中,也经常存在这种诱导凋亡的活性,而且与蓝藻是从极地、温带还是热带环境中采集的无关。与 Nostoc、Phormidium、Planktothrix 和 Pseudanabaena 相比,Anabaena 和 Microcystis 属中的蓝藻具有更丰富的活性。T 细胞淋巴瘤凋亡原在有机提取物中很常见,而诱导白血病细胞死亡的活性主要存在于水提取物中。这些蓝藻来自为公共卫生目的而建立的培养物库,以检测有毒蓝藻水华,其中 54 株通过小鼠生物测定法进行了毒性测试。我们发现蓝藻分离物中的诱导凋亡活性与其微囊藻毒素含量之间,以及与它们引起阳性标准小鼠生物测定的能力之间均无相关性。一些菌株产生了不止一种凋亡原,其在生物物理或生物学活性方面存在差异。实际上,有两个菌株除了含有一种针对 AML 细胞的凋亡原外,还含有一种针对 T 细胞淋巴瘤的微囊藻毒素。这项研究表明蓝藻培养物库作为生物活性化合物文库的潜力,因为培养了几十年的菌株产生了与小鼠生物测定法检测到的与水华相关的毒素无关的凋亡原。
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