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

Abstract

Highlights: Black-Right-Pointing-Pointer Ayanin diacetate as apoptotic inducer in leukemia cells. Black-Right-Pointing-Pointer Cell death was prevented by caspase inhibitors and by the overexpression of Bcl-x{sub L}. Black-Right-Pointing-Pointer The intrinsic and the extrinsic pathways are involved in the mechanism of action. Black-Right-Pointing-Pointer Death receptors are up-regulated and TRAIL enhances apoptotic cell death. -- 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{sub 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{sub 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:
; ; ;  [1]; ; ;  [2];  [3];  [1]
  1. Departamento de Bioquimica, Unidad Asociada al Consejo Superior de Investigaciones Cientificas, Universidad de Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria (Spain)
  2. Departamento de Quimica, Universidad de Las Palmas de Gran Canaria, Instituto Canario de Investigacion del Cancer, 35017 Las Palmas de Gran Canaria (Spain)
  3. Instituto de Productos Naturales y Agrobiologia, Consejo Superior de Investigaciones Cientificas, Avda. Astrofisico F. Sanchez 3, 38206 La Laguna, Tenerife (Spain)
Publication Date:
OSTI Identifier:
22210323
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 428; Journal Issue: 1; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADP; APOPTOSIS; CELL CYCLE; CELL PROLIFERATION; DEATH; FLAVONOIDS; LEUKEMIA; LYMPHOCYTES; MITOCHONDRIA; RECEPTORS; RIBOSE

Citation Formats

Marrero, Maria Teresa, Estevez, Sara, Negrin, Gledy, Quintana, Jose, Lopez, Mariana, Perez, Francisco J., Triana, Jorge, Leon, Francisco, and Estevez, Francisco, E-mail: festevez@dbbf.ulpgc.es. Ayanin diacetate-induced cell death is amplified by TRAIL in human leukemia cells. United States: N. p., 2012. Web. doi:10.1016/J.BBRC.2012.10.017.
Marrero, Maria Teresa, Estevez, Sara, Negrin, Gledy, Quintana, Jose, Lopez, Mariana, Perez, Francisco J., Triana, Jorge, Leon, Francisco, & Estevez, Francisco, E-mail: festevez@dbbf.ulpgc.es. Ayanin diacetate-induced cell death is amplified by TRAIL in human leukemia cells. United States. doi:10.1016/J.BBRC.2012.10.017.
Marrero, Maria Teresa, Estevez, Sara, Negrin, Gledy, Quintana, Jose, Lopez, Mariana, Perez, Francisco J., Triana, Jorge, Leon, Francisco, and Estevez, Francisco, E-mail: festevez@dbbf.ulpgc.es. Fri . "Ayanin diacetate-induced cell death is amplified by TRAIL in human leukemia cells". United States. doi:10.1016/J.BBRC.2012.10.017.
@article{osti_22210323,
title = {Ayanin diacetate-induced cell death is amplified by TRAIL in human leukemia cells},
author = {Marrero, Maria Teresa and Estevez, Sara and Negrin, Gledy and Quintana, Jose and Lopez, Mariana and Perez, Francisco J. and Triana, Jorge and Leon, Francisco and Estevez, Francisco, E-mail: festevez@dbbf.ulpgc.es},
abstractNote = {Highlights: Black-Right-Pointing-Pointer Ayanin diacetate as apoptotic inducer in leukemia cells. Black-Right-Pointing-Pointer Cell death was prevented by caspase inhibitors and by the overexpression of Bcl-x{sub L}. Black-Right-Pointing-Pointer The intrinsic and the extrinsic pathways are involved in the mechanism of action. Black-Right-Pointing-Pointer Death receptors are up-regulated and TRAIL enhances apoptotic cell death. -- 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{sub 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{sub 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.},
doi = {10.1016/J.BBRC.2012.10.017},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 428,
place = {United States},
year = {2012},
month = {11}
}