Endoplasmic reticulum stress associated with caspases-4 and-2 mediates korbazol-induced B-chronic lymphocytic leukemia cell apoptosis
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1811451
- author
- Popovic, S. ; Baskic, D. ; Djurdjevic, P. ; Zelen, I. ; Mitrovic, M. ; Nikolic, I. ; Avramovic, D. ; Radenkovic, Miljana LU and Arsenijevic, N.
- organization
- publishing date
- 2010
- 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
- 2016-04-01 14:37:51
- date last changed
- 2022-01-28 01:41:31
@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}}, keywords = {{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}}, }