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

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

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Received: 26 January 2014; in revised form: 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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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.

AMA Style

Liu L, Herfindal L, Jokela J, Shishido TK, Wahlsten M, Døskeland SO, Sivonen K. Cyanobacteria from Terrestrial and Marine Sources Contain Apoptogens Able to Overcome Chemoresistance in Acute Myeloid Leukemia Cells. Marine Drugs. 2014; 12(4):2036-2053.

Chicago/Turabian Style

Liu, Liwei; Herfindal, Lars; Jokela, Jouni; Shishido, Tania K.; Wahlsten, Matti; Døskeland, Stein O.; Sivonen, Kaarina. 2014. "Cyanobacteria from Terrestrial and Marine Sources Contain Apoptogens Able to Overcome Chemoresistance in Acute Myeloid Leukemia Cells." Mar. Drugs 12, no. 4: 2036-2053.


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