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Endoplasmic reticulum stress associated with caspases-4 and-2 mediates korbazol-induced B-chronic lymphocytic leukemia cell apoptosis

Popovic, S.; Baskic, D.; Djurdjevic, P.; Zelen, I.; Mitrovic, M.; Nikolic, I.; Avramovic, D.; Radenkovic, Miljana LU and Arsenijevic, N. (2010) In Journal of Buon 15(4). p.783-790
Abstract
Purpose: B-cell chronic lymphocytic leukemia (B-CLL) is an incurable disease that rapidly develops drug resistance. Therefore there is a need for identifying new agents that will improve the therapeutic outcome. Korbazol is a natural product known to exert cytotoxic effect on the in vitro survival of leukemic cells. The aim of this study was to investigate the mechanism of korbazol-induced apoptosis in B-CLL leukemic cells. Methods: Peripheral blood mononuclear cells from 10 B-CLL patients were used for assessing the effect of caspase inhibitors and chelator of intracellular Ca2+ Results: Cell death rate induced by the tested compound was decreased with the caspase-3 inhibitor Ac-DEVD-CHO, and the inhibitors of caspase-2 (Z-VDVAD-FMK) and... (More)
Purpose: B-cell chronic lymphocytic leukemia (B-CLL) is an incurable disease that rapidly develops drug resistance. Therefore there is a need for identifying new agents that will improve the therapeutic outcome. Korbazol is a natural product known to exert cytotoxic effect on the in vitro survival of leukemic cells. The aim of this study was to investigate the mechanism of korbazol-induced apoptosis in B-CLL leukemic cells. Methods: Peripheral blood mononuclear cells from 10 B-CLL patients were used for assessing the effect of caspase inhibitors and chelator of intracellular Ca2+ Results: Cell death rate induced by the tested compound was decreased with the caspase-3 inhibitor Ac-DEVD-CHO, and the inhibitors of caspase-2 (Z-VDVAD-FMK) and -4 (ZYVAD-FMK), but not with the caspase-9 inhibitor z-LEHD-FMK and caspase-8 inhibitor z-IETD-FMK No significant release of cytochrome C (cyt C) from mitochondria to the cytosol of B-CLL cells treated with korbazol was observed. Moreover, chelating of intracellular Ca2+ with BAPTA-AM almost completely abolished the cytotoxic effect of korbazol. Conclusion: Engagement of caspases-2 and -4 and mobilization of intracellular Ca2+ indicate involvement of endoplasmic reticulum (ER) stress in apoptosis induced by korbazol. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
korbazol, endoplasmic reticulum stress, chronic lymphocytic leukemia, apoptosis
in
Journal of Buon
volume
15
issue
4
pages
783 - 790
publisher
Zerbinis Medical Publ.
external identifiers
  • wos:000286539800025
  • scopus:78651412360
ISSN
1107-0625
language
English
LU publication?
yes
id
79c0a161-5622-4cbc-a9b1-573b3f18bdbb (old id 1811451)
date added to LUP
2011-03-02 14:05:02
date last changed
2018-05-29 11:00:48
@article{79c0a161-5622-4cbc-a9b1-573b3f18bdbb,
  abstract     = {Purpose: B-cell chronic lymphocytic leukemia (B-CLL) is an incurable disease that rapidly develops drug resistance. Therefore there is a need for identifying new agents that will improve the therapeutic outcome. Korbazol is a natural product known to exert cytotoxic effect on the in vitro survival of leukemic cells. The aim of this study was to investigate the mechanism of korbazol-induced apoptosis in B-CLL leukemic cells. Methods: Peripheral blood mononuclear cells from 10 B-CLL patients were used for assessing the effect of caspase inhibitors and chelator of intracellular Ca2+ Results: Cell death rate induced by the tested compound was decreased with the caspase-3 inhibitor Ac-DEVD-CHO, and the inhibitors of caspase-2 (Z-VDVAD-FMK) and -4 (ZYVAD-FMK), but not with the caspase-9 inhibitor z-LEHD-FMK and caspase-8 inhibitor z-IETD-FMK No significant release of cytochrome C (cyt C) from mitochondria to the cytosol of B-CLL cells treated with korbazol was observed. Moreover, chelating of intracellular Ca2+ with BAPTA-AM almost completely abolished the cytotoxic effect of korbazol. Conclusion: Engagement of caspases-2 and -4 and mobilization of intracellular Ca2+ indicate involvement of endoplasmic reticulum (ER) stress in apoptosis induced by korbazol.},
  author       = {Popovic, S. and Baskic, D. and Djurdjevic, P. and Zelen, I. and Mitrovic, M. and Nikolic, I. and Avramovic, D. and Radenkovic, Miljana and Arsenijevic, N.},
  issn         = {1107-0625},
  keyword      = {korbazol,endoplasmic reticulum stress,chronic lymphocytic leukemia,apoptosis},
  language     = {eng},
  number       = {4},
  pages        = {783--790},
  publisher    = {Zerbinis Medical Publ.},
  series       = {Journal of Buon},
  title        = {Endoplasmic reticulum stress associated with caspases-4 and-2 mediates korbazol-induced B-chronic lymphocytic leukemia cell apoptosis},
  volume       = {15},
  year         = {2010},
}