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

作者：Teresa Marrero Maria; EstevezA Sara; Negrin Gledy; Quintana Jose; Lopez Mariana; Perez Francisco J; Triana Jorge; Leon Francisco; Estevez Francisco^*

来源：Biochemical and Biophysical Research Communications, 2012, 428(1): 116-120.

DOI：10.1016/j.bbrc.2012.10.017

• Apoptosis
• Flavonoids
• Cytotoxic activity
• Caspases
• Poly(ADP-ribose) polymerase
• Death receptors

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.

• 出版日期2012-11-9