Microcystis aeruginosa, which spreads in five continents in the world and reported in drinking water resources in 257 countries, is a dangerous microalgae for human and animal health due to its toxins. The aim of current study was to evaluate the effects of M. aeruginosa extract and its chromatographically separated fractions on human endothelial cells. In this context, crude extract was prepared from M. aeruginosa cultured in BG-11 medium, and it was fractionated by an optimized HPLC method. Algae extract and its six fractions were then analyzed for their cytotoxic effects on ECV304 using MTT assay. The results revealed that algae extract inhibited ECV304 cells by around 72%, a higher percentage than all fractions. The most toxic fraction was the first fraction, which inhibited the cells by 55%. Other fractions, except the third one, were also toxic with 35-40% inhibition percentages. Third fraction and certain doses of some fractions showed proliferative activity on ECV304 cells. These results showed that the activities of the total extract and its fractions in promoting or inhibiting cell proliferation varied depending on not only the content but also the treatment dose.
This study was supported by the Istanbul University Research Foundation, Turkey
Project Number
FYL-2016-21655
Thanks
We would like to thank Prof. Dr. Reyhan Akçaalan Albay for her supply of cyanobacteria and Associate Prof. Dr. Belkıs Atasever Arslan for her supply of ECV304 cell line.
References
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Bryant, D.A. (1994). Gene nomenclature recommendations for green photosynthetic bacteria and heliobacteria‖. Photosynthesis Research, 41, 27-28. https://doi.org/10.1007/BF02184142
Campos, A., Vasconcelos, V. (2010). Molecular mechanisms of microcystin toxicity in animal cells. International Journal of Molecular Sciences, 11, 268-287. https://doi.org/10.3390/ijms11010268
Carmichael, W.W. (1994). The toxins of cyanobacteria. Scientific American, 270(1), 78-86. https://doi.org/10.1038/scientificamerican0194-78
Chen, H., Zhao, J., Li, Y., He, L.X., Huang, Y.J., Shu, W.Q., Cao, J., Liu, W.B., Liu, J.Y. (2018). Gene expression network regulated by DNA methylation and microRNA during microcystin-leucine arginine induced malignant transformation in human hepatocyte L02 cells. Toxicology Letters, 289(1), 42-53. https://doi.org/10.1016/j.toxlet.2018.03.003
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Entfellner, E., Freil, M., Christiansen, G., Deng, L., Blom, J., Kurmayer, R. (2017). Evolution of anabaenopeptin peptide structural variability in the cyanobacterium Planktot-hrix. Frontier in Microbiology, 8, 1-13. https://doi.org/10.3389/fmicb.2017.00219
Faassen, E.J., Lürling, M. (2013). Occurrence of the microcystins MC-LW and MC-LF in dutch surface waters and their contribution to total microcystin toxicity. Marine Drugs, 11(7), 2643-2654. https://doi.org/10.3390/md11072643
Foroh, M.O. Mahrouz, D. (2016). The effect of cyanobacteria Nostoc. Sp Isc 113 polysaccharide on the proliferation and adhesion of endothelial cells to repair the vessel, Journal Of Animal Physiology And Development, 9(33), 1-11.
Fosse, J.H., Haraldsen, G., Falk, K., Edelmann, R. (2021). Endothelial cells in emerging viral infections. Frontiers in Cardiovascular Medicine, 8, 95. https://doi.org/10.3389/fcvm.2021.619690
Gutiérrez-Praena, D., Pichardo, S., Jos, A., Moreno, F.J., Cameán, A.M. (2012). Alterations observed in the endothelial HUVEC cell line exposed to pure cylindrospermopsin. Chemosphere, 89(9), 1151-1160. https://doi.org/10.1016/j.chemosphere.2012.06.023
Gutiérrez-Praena, D., Guzmán-Guillén, R., Pichardo, S., Moreno, F.J. (2019). Cytotoxic and morphological effects of microcystin-LR, cylindrospermopsin, and their combinations on the human hepatic cell line HepG2. Environmental Toxicology, 34, 240-251. https://doi.org/10.1002/tox.22679
Harke, M.J., Steffen, M.M., Gobler, C.J., Otten, T.G., Wilhelm, S.W., Wood, S.A., Paerl, H.W. (2016). A review of the global ecology, genomics, and biogeography of the toxic cyanobacterium, Microcystis sp. Harmful Algae, 54, 4-20. https://doi.org/10.1016/j.hal.2015.12.007
Herrera, N., Herrera, C., Ortíz, I., Orozco, L., Robledo, S., Agudelo, D., Echeverria, F. (2018). Genotoxicity and cytotoxicity of three microcystin-LR containing cyanobacterial samples from Antioquia, Colombia. Toxicon, 154, 50-59. https://doi.org/10.1016/j.toxicon.2018.09.011
Karjalainen, M., Engstrom-Ost, J., Korpinen, S., Peltonen, H., Paakkonen, J.P., Ronkkonen, S., Suikkanen, S., Viitasalo, M. (2007). Ecosystem consequences of cyanobacteria in the northern Baltic Sea. Ambio, 36, 195-202. https://doi.org/10.1579/0044-7447
Khalid, M.N., Shameel, M., Ahmad, V., Shahzad, S., Leghari, S. (2010). Studies on the bioactivity and phycochemistry of Microcystis aeruginosa (Cyanophycota) from Sindh. Pakistan Journal of Botany, 42, 2635-2646.
Kim, S.K., Chojnacka, K. (2015). Marine Algae Extracts Processes, Products, and Applications, Wroclaw: Wiley-VCN, p. 227-346, ISBN: 9783527337088
Kotak, B.G., Lam, A.K., Prepas, E.E., Kenefi, S.L., Hrudey, S.E. (1995). Variability of the hepatotoxin, microcystin-LR, in hypereurophic drinking water lakes. Journal Phycology, 31, 248-263. https://doi.org/10.1111/j.0022-3646.1995.00248.x
Krüger-Genge, A., Blocki, A., Franke, R.P., Jung, F. (2019). Vascular endothelial cell biology: an update. International Journal of Molecular Sciences, 20(18), 4411-4433. https://doi.org/10.3390/ijms20184411
Kurmayer, R. (2011). The toxic cyanobacterium Nostoc sp. strain 152 produces highest amounts of microcystin and nostophycin under stress conditions. Journal of Phycology, 47, 200-207. https://doi.org/10.1111/j.1529-8817.2010.00931.x
Laude, K., Thuillez, C., Richard, V. (2001). Coronary endothelial dysfunction after ischemia and reperfusion: a new therapeutic target? Brazilian Journal of Medical and Biological Research, 34(1) 1-7. https://doi.org/10.1590/S0100-879X2001000100001
Lawton, L.A., Edwards, C., Codd, G.A. (1994). Extraction and high-performance liquid chromatographic method for the determination of microcystins in raw and treated waters. Analyst, 11(9), 1525- 1530. https://doi.org/10.1039/AN9941901525
Moreno, I.M., Maraver, J., Aguete, E.C., Leao, M., Gago-Martínez, A., Cameán, A.M. (2004). Decomposition of microcystin-LR, microcystin-RR, and microcystin-YR in water samples submitted to in vitro dissolution tests. Journal of Agriculture Food Chemistry, 52(19), 5933-5938. https://doi.org/10.1021/jf0489668
Paiva, L., Lima, E., Neto, A.I., Baptista, J. (2017). Angiotensin I-converting enzyme (ACE) inhibitory activity, antioxidant properties, phenolic content and amino acid profiles of Fucus spiralis protein hydrolysate fractions. Marine Drugs, 15(10), 311-329. https://doi.org/10.3390/md15100311
Pearson, L., Mihali, T., Moffitt, M., Kellmann, R., Neilan, B. (2010). On the chemistry, toxicology and genetics of the cyanobacterial toxins, microcystin, nodularin, saxitoxin and cylindrospermopsin. Marine Drugs, 8, 1650-1680. https://doi.org/10.3390/md8051650
Pırıldar, S., Sütlüpınar, N., Atasever, B., Erdem-Kuruca, S., Papouskova, B., Šimánek, V. (2010). Chemical constituents of the different parts of Colchicum baytopiorum (Liliaceae) and their cytotoxic activities on K562 and HL60 cell-lines. Pharmaceutical Biology, 48(1), 32-39. https://doi.org/10.3109/13880200903029373
Piyathilaka, M.A.P.C., Pathmalal, M.M., Tennekoon, K.H., De Silva, B.G.D.N.K., Samarakoon, S.R., Chanthirika, S. (2015). Microcystin-LR-induced cytotoxicity and apoptosis in human embryonic kidney and human kidney adenocarcinoma cell lines. Microbiology, 161, 819-828. https://doi.org/10.1099/mic.0.000046
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Kaan Yılancıoğlu
Üsküdar University, Faculty of Engineering and Natural Sciences, Department of Molecular Biology and Genetics0000-0003-0740-5580Türkiye
Kuşoğlu Gültekin, S., Mertoğlu Kamalı, E., Yılancıoğlu, K., Arda, N. (2022). Dose-dependent cytotoxic and proliferative effects of Microcystis aeruginosa extract and its fractions on human endothelial cells. Aquatic Research, 5(2), 117-128. https://doi.org/10.3153/AR22011
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