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Mar. Drugs 2014, 12(4), 2036-2053; doi:10.3390/md12042036

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

1
Division of Microbiology and Biotechnology, Department of Food and Environmental Sciences, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland
2
Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway
3
Translational Signaling Group, Haukeland University Hospital, Jonas Lies vei 91, N-5009 Bergen, Norway
*
Author to whom correspondence should be addressed.
Received: 26 January 2014 / Revised: 13 March 2014 / Accepted: 18 March 2014 / Published: 3 April 2014
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Abstract

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.
Keywords: cyanobacteria; acute myeloid leukemia; hepatocyte; apoptosis; p53; Bcl-2; microcystin; nodularin cyanobacteria; acute myeloid leukemia; hepatocyte; apoptosis; p53; Bcl-2; microcystin; nodularin
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Liu, L.; Herfindal, L.; Jokela, J.; Shishido, T.K.; Wahlsten, M.; Døskeland, S.O.; Sivonen, K. Cyanobacteria from Terrestrial and Marine Sources Contain Apoptogens Able to Overcome Chemoresistance in Acute Myeloid Leukemia Cells. Mar. Drugs 2014, 12, 2036-2053.

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