Astragalin heptaacetate-induced cell death in human leukemia cells is dependent on caspases and activates the MAPK pathway.

Abstract

Flavonoids are naturally occurring polyphenolic compounds and are among the most promising anticancer agents. Here we demonstrate that the flavonoid derivative astragalin heptaacetate (AHA) induces cell death. This was prevented by the non-specific caspase inhibitors z-VAD-fmk and Q-VD-OPH, and reduced by the selective caspase-4 inhibitor z-LEVD-fmk. AHA-induced cell death was found to be: (i) associated with the release of cytochrome c, (ii) suppressed by the overexpression of Bcl-x(L), (iii) amplified by inhibition of extracellular signal-regulated kinases (ERKs) 1/2 and c-jun NH(2)-terminal kinases/stress activated protein kinases (JNK/SAPK) signaling, and (iv) completely abrogated by the free-radical scavenger N-acetyl-l-cysteine.

• Authors: Olga Burmistrova, José Quintana, Jesús G Díaz, Francisco Estévez
• Journal: Cancer letters (Cancer Lett) Vol. 309 Issue 1 Pg. 71-7 (Oct 01 2011) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 21658841 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Amino Acid Chloromethyl Ketones
• Caspase Inhibitors
• Cysteine Proteinase Inhibitors
• Glycosides
• Kaempferols
• Proto-Oncogene Proteins c-bcl-2
• Quinolines
• astragalin heptaacetate
• benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
• quinoline-val-asp(OMe)-CH2-OPH
• Cytochromes c
• Caspases

Topics

• Amino Acid Chloromethyl Ketones (pharmacology)
• Apoptosis (drug effects, physiology)
• Caspase Inhibitors
• Caspases (metabolism)
• Cell Death (drug effects)
• Cell Proliferation (drug effects)
• Cysteine Proteinase Inhibitors (pharmacology)
• Cytochromes c (metabolism)
• Glycosides (pharmacology)
• HL-60 Cells
• Humans
• Kaempferols (pharmacology)
• Leukemia (enzymology, pathology)
• MAP Kinase Signaling System (drug effects)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Quinolines (pharmacology)