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Akihisa, T. et al.

Toshihiro Akihisa, Takashi Kikuchi, Hisashi Nagai, Koichi Ishii, Keiichi Tabata, Takashi Suzuki,

4-Hydroxyderricin from Angelica keiskei roots induces caspase-dependent apoptotic cell death in HL60 human leukemia cells.

The ethyl acetate (EtOAc)-soluble fraction of a methanol extract of Angelica keiskei roots exhibited cytotoxic activity against 4 human tumor cell lines, HL60 (leukemia), CRL1579 (melanoma), A549 (lung), and AZ521 (stomach). Nine chalcones (1-9), 5 coumarins (10-14), and 4 flavanones (15-18), isolated from the EtOAc-soluble fraction, were examined for their cytotoxic activities in the 4 human tumor cell lines. Among the compounds tested, 4-hydroxyderricin (2), a major chalcone constituent, exhibited potent cytotoxic activities in all 4 tumor cell lines with IC(50) values of 5.5 µM (HL60), 4.8 µM (CRL1579), 10.2 µM (A549), and 4.2 µM (AZ521). 4-Hydroxyderricin induced early apoptosis in HL60 cells, observed as membrane phospholipid exposure in flow cytometry. Western blot analysis showed that 4-hydroxyderricin markedly reduced the levels of procaspases-3, -8, and -9, while increasing the levels of cleaved caspases-3, -8, and -9. In addition, 4-hydroxyderricin exhibited potent inhibitory activity on human DNA topoisomerase (Topo) II (IC(50) 21.9 µM). These results suggested that 4-hydroxyderricin induces apoptotic cell death in HL60 via both the death receptor-mediated pathway and the mitochondrial pathway by, at least in part, Topo II inhibition. 4-Hydroxyderricin may therefore hold promise as an effective antitumor agent.[1]

References

4-Hydroxyderricin from Angelica keiskei roots induces caspase-dependent apoptotic cell death in HL60 human leukemia cells. Akihisa, T., Kikuchi, T., Nagai, H., Ishii, K., Tabata, K., Suzuki, T. J. Oleo. Sci (2011) [Pubmed]

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