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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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Cyanobacterial extracts induce a synergistic apoptotic response with daunorubicin in acute myeloid leukemia cells, but not in cardiomyoblasts. Rat acute myeloid leukemia cells without (A) or with enforced expression of the survival factor LEDGF/p75 (B), or cardiomyoblasts (C), were incubated for 18 hours with cyanobacterial extracts alone or in combination with daunorubicin (DNR) (white and black columns, respectively) before fixation, staining and assessment of apoptosis as described in the legend to Figure 1. The results are mean and SEM, n = 3.
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f6-marinedrugs-08-02659: Cyanobacterial extracts induce a synergistic apoptotic response with daunorubicin in acute myeloid leukemia cells, but not in cardiomyoblasts. Rat acute myeloid leukemia cells without (A) or with enforced expression of the survival factor LEDGF/p75 (B), or cardiomyoblasts (C), were incubated for 18 hours with cyanobacterial extracts alone or in combination with daunorubicin (DNR) (white and black columns, respectively) before fixation, staining and assessment of apoptosis as described in the legend to Figure 1. The results are mean and SEM, n = 3.

Mentions: Since M44, and to a lesser extent M27 and M30, differed from daunorubicin in cell death mechanism and in efficiency against LEDGF/p75 overexpressing cells, they could be useful adjuncts to daunorubicin. In fact, all three synergized strongly with daunorubicin to induce apoptosis whether the AML cells had enforced expression of LEGDF/p75 or not (Figure 6A and B). This suggests that the cyanobacterial apoptogens have potential to enhance the efficiency of daunorubicin, also in cells expressing the chemoresistance-associated LEDGF/p75.


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)

Cyanobacterial extracts induce a synergistic apoptotic response with daunorubicin in acute myeloid leukemia cells, but not in cardiomyoblasts. Rat acute myeloid leukemia cells without (A) or with enforced expression of the survival factor LEDGF/p75 (B), or cardiomyoblasts (C), were incubated for 18 hours with cyanobacterial extracts alone or in combination with daunorubicin (DNR) (white and black columns, respectively) before fixation, staining and assessment of apoptosis as described in the legend to Figure 1. The results are mean and SEM, n = 3.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6-marinedrugs-08-02659: Cyanobacterial extracts induce a synergistic apoptotic response with daunorubicin in acute myeloid leukemia cells, but not in cardiomyoblasts. Rat acute myeloid leukemia cells without (A) or with enforced expression of the survival factor LEDGF/p75 (B), or cardiomyoblasts (C), were incubated for 18 hours with cyanobacterial extracts alone or in combination with daunorubicin (DNR) (white and black columns, respectively) before fixation, staining and assessment of apoptosis as described in the legend to Figure 1. The results are mean and SEM, n = 3.
Mentions: Since M44, and to a lesser extent M27 and M30, differed from daunorubicin in cell death mechanism and in efficiency against LEDGF/p75 overexpressing cells, they could be useful adjuncts to daunorubicin. In fact, all three synergized strongly with daunorubicin to induce apoptosis whether the AML cells had enforced expression of LEGDF/p75 or not (Figure 6A and B). This suggests that the cyanobacterial apoptogens have potential to enhance the efficiency of daunorubicin, also in cells expressing the chemoresistance-associated LEDGF/p75.

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