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Marine benthic cyanobacteria contain apoptosis-inducing activity synergizing with daunorubicin to kill leukemia cells, but not cardiomyocytes.

Oftedal L, Selheim F, Wahlsten M, Sivonen K, Døskeland SO, Herfindal L - Mar Drugs (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway. linn.oftedal@biomed.uib.no

ABSTRACT
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.

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Apoptotic morphology induced by cyanobacterial extracts in AML cells. Rat leukemia cells (A: control) were added the aqueous extract of the cyanobacterial strain M27 (B), M30 (C), M44 (D) or 50 nM daunorubicin (DNR, E) as described in the legend to Figure 1, and photomicrographs were taken using differential interference contrast (upper) and UV (lower). Bar represent 10 μm.
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f4-marinedrugs-08-02659: Apoptotic morphology induced by cyanobacterial extracts in AML cells. Rat leukemia cells (A: control) were added the aqueous extract of the cyanobacterial strain M27 (B), M30 (C), M44 (D) or 50 nM daunorubicin (DNR, E) as described in the legend to Figure 1, and photomicrographs were taken using differential interference contrast (upper) and UV (lower). Bar represent 10 μm.

Mentions: Cell death induced by M27, M30 or M44 had the morphological hallmarks of apoptosis, such as chromatin condensation, nuclear fragmentation, surface budding and shedding of apoptotic bodies (Figure 4A–D). The apoptotic phenotype was as striking as the one observed in cells incubated with the benchmark anti-AML drug daunorubicin (Figure 4E).


Marine benthic cyanobacteria contain apoptosis-inducing activity synergizing with daunorubicin to kill leukemia cells, but not cardiomyocytes.

Oftedal L, Selheim F, Wahlsten M, Sivonen K, Døskeland SO, Herfindal L - Mar Drugs (2010)

Apoptotic morphology induced by cyanobacterial extracts in AML cells. Rat leukemia cells (A: control) were added the aqueous extract of the cyanobacterial strain M27 (B), M30 (C), M44 (D) or 50 nM daunorubicin (DNR, E) as described in the legend to Figure 1, and photomicrographs were taken using differential interference contrast (upper) and UV (lower). Bar represent 10 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2992999&req=5

f4-marinedrugs-08-02659: Apoptotic morphology induced by cyanobacterial extracts in AML cells. Rat leukemia cells (A: control) were added the aqueous extract of the cyanobacterial strain M27 (B), M30 (C), M44 (D) or 50 nM daunorubicin (DNR, E) as described in the legend to Figure 1, and photomicrographs were taken using differential interference contrast (upper) and UV (lower). Bar represent 10 μm.
Mentions: Cell death induced by M27, M30 or M44 had the morphological hallmarks of apoptosis, such as chromatin condensation, nuclear fragmentation, surface budding and shedding of apoptotic bodies (Figure 4A–D). The apoptotic phenotype was as striking as the one observed in cells incubated with the benchmark anti-AML drug daunorubicin (Figure 4E).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway. linn.oftedal@biomed.uib.no

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus