Ayanin diacetate-induced cell death is amplified by TRAIL in human leukemia cells.

Abstract

Here we demonstrate that the semi-synthetic flavonoid ayanin diacetate induces cell death selectively in leukemia cells without affecting the proliferation of normal lymphocytes. Incubation of human leukemia cells with ayanin diacetate induced G(2)-M phase cell cycle arrest and apoptosis which was prevented by the non-specific caspase inhibitor z-VAD-fmk and reduced by the overexpression of Bcl-x(L). Ayanin diacetate-induced cell death was found to be associated with: (i) loss of inner mitochondrial membrane potential, (ii) the release of cytochrome c, (iii) the activation of multiple caspases, (iv) cleavage of poly(ADP-ribose) polymerase and (v) the up-regulation of death receptors for TRAIL, DR4 and DR5. Moreover, the combined treatment with ayanin diacetate and TRAIL amplified cell death, compared to single treatments. These results provide a basis for further exploring the potential applications of this combination for the treatment of cancer.

• Authors: María Teresa Marrero, Sara Estévez, Gledy Negrín, José Quintana, Mariana López, Francisco J Pérez, Jorge Triana, Francisco León, Francisco Estévez
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 428 Issue 1 Pg. 116-20 (Nov 09 2012) ISSN: 1090-2104 [Electronic] United States
• PMID: 23063980 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Flavones
• Flavonoids
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• TNF-Related Apoptosis-Inducing Ligand
• TNFRSF10A protein, human
• ayanin
• ayanin diacetate
• Caspases

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Caspases (metabolism)
• Cell Survival (drug effects)
• Flavones (pharmacology)
• Flavonoids (pharmacology)
• G2 Phase Cell Cycle Checkpoints (drug effects)
• HL-60 Cells
• Humans
• Leukemia (enzymology, metabolism)
• Receptors, TNF-Related Apoptosis-Inducing Ligand (metabolism)
• TNF-Related Apoptosis-Inducing Ligand (pharmacology)
• U937 Cells
• Up-Regulation