Cyanobacteria from terrestrial and marine sources contain apoptogens able to overcome chemoresistance in acute myeloid leukemia cells.
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.
Division of Microbiology and Biotechnology, Department of Food and Environmental Sciences, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland. liwei.liu@helsinki.fi.
Liwei
L
Liu
Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway. lars.herfindal@biomed.uib.no.
Lars
L
Herfindal
Division of Microbiology and Biotechnology, Department of Food and Environmental Sciences, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland. jouni.jokela@helsinki.fi.
Jouni
J
Jokela
Division of Microbiology and Biotechnology, Department of Food and Environmental Sciences, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland. tania.shishido@helsinki.fi.
Tania Keiko
TK
Shishido
Division of Microbiology and Biotechnology, Department of Food and Environmental Sciences, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland. matti.wahlsten@helsinki.fi.
Matti
M
Wahlsten
Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway. stein.doskeland@biomed.uib.no.
Stein Ove
SO
Døskeland
Division of Microbiology and Biotechnology, Department of Food and Environmental Sciences, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland. kaarina.sivonen@helsinki.fi.
Kaarina
K
Sivonen
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D000458:Cyanobacteria / Q000737:chemistry* / Q000302:isolation & purification; D019008:Drug Resistance, Neoplasm; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D051381:Rats
D000970:Antineoplastic Agents