A Novel Cyanobacterial Nostocyclopeptide is a Potent Antitoxin against Microcystins

Jokela, Jouni; Herfindal, Lars; Wahlsten, Matti; Permi, Perttu; Selheim, Frode; Vasconcelos, Vítor; Døskeland, Stein Ove; Sivonen, Kaarina

doi:10.1002/cbic.201000179

Cited by 48 publications

(62 citation statements)

References 31 publications

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“…The extracts of L7-A, L36-A, L38-A, L32-O, L33-O and L38-O, which were shown to contain microcystin by LC-MS, had no effect on triggering the apoptosis of HEK293T cells. This demonstrates the strength of both methods: LC-MS has higher sensitivity towards toxins, can detect very low amounts and will not be affected by the presence of toxin inhibitors [36]. However, the cell-based assay can detect activity from unknown toxin variants.…”

Section: Resultsmentioning

confidence: 99%

Cyanobacteria from Terrestrial and Marine Sources Contain Apoptogens Able to Overcome Chemoresistance in Acute Myeloid Leukemia Cells

et al. 2014

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In this study, we investigated forty cyanobacterial isolates from biofilms, gastropods, brackish water and symbiotic lichen habitats. Their aqueous and organic extracts were used to screen for apoptosis-inducing activity against acute myeloid leukemia cells. A total of 28 extracts showed cytotoxicity against rat acute myeloid leukemia (IPC-81) cells. The design of the screen made it possible to eliminate known toxins, such as microcystins and nodularin, or known metabolites with anti-leukemic activity, such as adenosine and its analogs. A cytotoxicity test on human embryonic kidney (HEK293T) fibroblasts indicated that 21 of the 28 extracts containing anti-acute myeloid leukemia (AML) activity showed selectivity in favor of leukemia cells. Extracts L26-O and L30-O were able to partly overcome the chemotherapy resistance induced by the oncogenic protein Bcl-2, whereas extract L1-O overcame protection from the deletion of the tumor suppressor protein p53. In conclusion, cyanobacteria are a prolific resource for anti-leukemia compounds that have potential for pharmaceutical applications. Based on the variety of cellular responses, we also conclude that the different anti-leukemic compounds in the cyanobacterial extracts target different elements of the death machinery of mammalian cells.

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Section: Resultsmentioning

confidence: 99%

Cyanobacteria from Terrestrial and Marine Sources Contain Apoptogens Able to Overcome Chemoresistance in Acute Myeloid Leukemia Cells

et al. 2014

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“…7). Nostocyclopeptides, a cyclic hexapeptide, showed weak cytotoxicity against KB (a human nasopharyngeal carcinoma) and LoVo (a human colorectal adenocarcinoma) cell lines and were devoid of antifungal and antibacterial activities (Golakoti et al 2001, Becker et al 2004, Jokela et al 2010.…”

Section: Discussionmentioning

confidence: 99%

Identification and toxigenic potential of a Nostoc sp.

Nowruzi¹,

Khavari-Nejad²,

Sivonen³

et al. 2012

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Cyanobacteria are well known for their production of a multitude of highly toxic and / or allelopathic compounds. Among the photosynthetic microorganisms, cyanobacteria, belonging to the genus Nostoc are regarded as good candidate for producing biologically active secondary metabolites which are highly toxic to humans and other animals. Since so many reports have been published on the poisoning of different animals from drinking water contaminated with cyanobacteria toxins, it might be assumed that bioactive compounds are found only in aquatic species causes toxicity. However, the discovery of several dead dogs, mice, ducks, and fish around paddy fields, prompted us to study the toxic compounds in a strain of Nostoc which is most abundant in the paddy fields of Iran, using polymerase chain reaction and liquid chromatography coupled with a diode array detector and mass spectrophotometer. Results of molecular analysis demonstrated that the ASN_M strain contains the nosF gene. Also, the result of ion chromatograms and MS 2 fragmentation patterns showed that while there were three different peptidic compound classes (anabaenopeptin, cryptophycin, and nostocyclopeptides), there were no signs of the presence of anatoxin-a, homoanatoxin-a, hassallidin or microcystins. Moreover, a remarkable antifungal activity was identified in the methanolic extracts. Based on the results, this study suggests that three diverse groups of potentially bioactive compounds might account for the death of these animals. This case is the first documented incident of toxicity from aquatic cyanobacteria related intoxication in dogs, mice, and aquatic organisms in Iran.Key Words: cyanobacteria; natural bioactive compound; Nostoc; toxicity INTRODUCTIONThe genus Nostoc is an ecologically, morphologically, and physiologically diverse genus of microorganisms inhabiting soils, and represents large reservoir of potentially valuable natural compounds (Dembitsky and Řezanka 2005). The ecological significance of the Nostoc species extends beyond the compounds which they primarily known to produce, as many of these organisms are capable of modifying their habitats through the synthesis of biologically active products (Ehrenreich et al. 2005). These compounds demonstrate a diverse range of biological activities and chemical structures, including novel cyclic and linear lipopeptides, fatty acids, alkaloids, and other organic chemicals (Dittmann et al. 2001). A large number of novel antimicrobial agents have been identiReceived September 16, 2012, Accepted November 20, 2012 *Corresponding Author E-mail: bahare77biol@yahoo.com Tel: +98-91-1371-0956, Fax: +98-21-8884-8940 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 304 1,500-2,000 lux for two weeks (Kaushik 1987). Three small fragments of growing co...

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“…A novel compound, nostocyclopeptide, has been found to be produced by a Nostoc isolate from the Baltic Sea (Jokela et al, 2010). This potent cyclic peptide is an inhibitor of microcystin-induced apoptosis in hepatocytes, an activity not previously associated with cyanobacterial natural compounds.…”

Section: Further Cyanotoxinsmentioning

confidence: 99%

Planktonic and benthic cyanobacteria of European brackish waters: a perspective on estuaries and brackish seas

Lopes

Vasconcelos

2011

European Journal of Phycology

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Cyanobacteria are photosynthetic organisms found in aquatic and terrestrial biotopes and ecosystems throughout the world. Marine and freshwater cyanobacteria have been extensively studied due to the toxic hazards that some of them create and biotechnological interest. In contrast, the cyanobacteria of brackish waters have been less studied despite being able to form toxic blooms like their freshwater and marine counterparts. We review the occurrence, diversity and toxicity of cyanobacteria species in the brackish waters of Europe, mainly estuaries and brackish environments of the Atlantic Ocean and the Mediterranean and Baltic Seas. The dominant cyanobacteria belong mainly to the planktonic genera Nodularia, Aphanizomenon, Microcystis and Anabaena, but also the benthic forms of Anabaena and Phormidium. Most genera from brackish waters are reported to be hepatotoxin producers (microcystin and nodularin). However, anatoxin-a and other bioactive compounds (e.g. apoptogens) can also be found and are produced exclusively by benthic forms. Nodularin is the best-characterized brackish-water cyanotoxin, being primarily produced by N. spumigena. Data are presented on cyanotoxin production, accumulation, and potential food chain transfer, with a particular focus on nodularin, which induces multiple effects on food-chain dynamics. Microcystins and anatoxin-a are also considered. Potential risks to animals and humans from cyanotoxin exposure are discussed, although reports of animal poisoning by brackish-water toxic cyanobacteria are scarce and no cases of human intoxication are yet known.

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A Novel Cyanobacterial Nostocyclopeptide is a Potent Antitoxin against Microcystins

Cited by 48 publications

References 31 publications

Cyanobacteria from Terrestrial and Marine Sources Contain Apoptogens Able to Overcome Chemoresistance in Acute Myeloid Leukemia Cells

Cyanobacteria from Terrestrial and Marine Sources Contain Apoptogens Able to Overcome Chemoresistance in Acute Myeloid Leukemia Cells

Identification and toxigenic potential of a Nostoc sp.

Planktonic and benthic cyanobacteria of European brackish waters: a perspective on estuaries and brackish seas

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