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Calactin - a small molecule induces DNA damage and histione modification in leukemia cells

ABSTRACT: Calactin is a small molecule isolated from the Chinese herb Asclepias curassavica. We found that calactin induced DNA damage, G2/M arrest of cell cycle, and apoptosis. The calactin also increased the H2AX and Chk2 phosphorylation, which resulted in the decrease of Cdc25C and cdk1 expressions, indicating that calactin-induced G2/M arrest. Moreover, we observed that calactin-induced DNA fragmentation (DNA ladder), PARP cleavage, increase in Bad and Bax levels, and decrease in Bcl-2 and Bcl-xl expressions, which results in apoptosis. Furthermore, calactin modulates the histone modification enzymes Aurora B, SET8, MSK1, PCAF, and Gcn5, which result in H3K9, H3K18, and H3K23 acetylation, H3S10 and H3S28 phosphorylation, and H4K20 methylation. Docking results showed that calactin has a tendency to bind the active site of TOP1.

ORGANISM(S): Homo sapiens

PROVIDER: GSE20928 | GEO | 2011/03/31

SECONDARY ACCESSION(S): PRJNA124367

REPOSITORIES: GEO

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Calactin - a small molecule induces DNA damage and histione modification in leukemia cells

Project description:Calactin is a small molecule isolated from the Chinese herb Asclepias curassavica. We found that calactin induced DNA damage, G2/M arrest of cell cycle, and apoptosis. The calactin also increased the H2AX and Chk2 phosphorylation, which resulted in the decrease of Cdc25C and cdk1 expressions, indicating that calactin-induced G2/M arrest. Moreover, we observed that calactin-induced DNA fragmentation (DNA ladder), PARP cleavage, increase in Bad and Bax levels, and decrease in Bcl-2 and Bcl-xl expressions, which results in apoptosis. Furthermore, calactin modulates the histone modification enzymes Aurora B, SET8, MSK1, PCAF, and Gcn5, which result in H3K9, H3K18, and H3K23 acetylation, H3S10 and H3S28 phosphorylation, and H4K20 methylation. Docking results showed that calactin has a tendency to bind the active site of TOP1. This project includes 6 human leukemia K562 cells, 3 for treated 0.15mM calactin for 12hr and the others for control (untreated) samples.

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