Marine benthic cyanobacteria contain apoptosis-inducing activity synergizing with daunorubicin to kill leukemia cells, but not cardiomyocytes.
The potential of marine benthic cyanobacteria as a source of anticancer drug candidates was assessed in a screen for induction of cell death (apoptosis) in acute myeloid leukemia (AML) cells. Of the 41 marine cyanobacterial strains screened, more than half contained cell death-inducing activity. Several strains contained activity against AML cells, but not against non-malignant cells like hepatocytes and cardiomyoblasts. The apoptotic cell death induced by the various strains could be distinguished by the role of caspase activation and sensitivity to the recently detected chemotherapy-resistance-associated prosurvival protein LEDGF/p75. One strain (M44) was particularly promising since its activity counteracted the protective effect of LEDGF/p75 overexpressed in AML cells, acted synergistically with the anthracycline anticancer drug daunorubicin in AML cells, and protected cardiomyoblasts against the toxic effect of anthracyclines. We conclude that culturable benthic marine cyanobacteria from temperate environments provide a promising and hitherto underexploited source for novel antileukemic drugs.
Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway. linn.oftedal@biomed.uib.no
Linn
L
Oftedal
Frode
F
Selheim
Matti
M
Wahlsten
Kaarina
K
Sivonen
Stein Ove
SO
Døskeland
Lars
L
Herfindal
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D000458:Cyanobacteria / Q000737:chemistry* / Q000378:metabolism; D003630:Daunorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012623:Seawater / Q000382:microbiology; D013873:Thionucleotides / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents; C504649:PSIP1 protein, human; D013873:Thionucleotides; D014157:Transcription Factors; C408162:oblimersen; D020169:Caspases; D003630:Daunorubicin