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Doxorubicin-induced death in neuroblastoma does not involve death receptors in S-type cells and is caspase-independent in N-type cells.
Oncogene. 2002 Sep 05; 21(39):6132-7.O

Abstract

Death induced by doxorubicin (dox) in neuroblastoma (NB) cells was originally thought to occur via the Fas pathway, however since studies suggest that caspase-8 expression is silenced in most high stage NB tumors, it is more probable that dox-induced death occurs via a different mechanism. Caspase-8 silenced N-type invasive NB cell lines LAN-1 and IMR-32 were investigated for their sensitivity to dox, and compared to S-type noninvasive SH-EP NB cells expressing caspase-8. All cell lines had similar sensitivities to dox, independently of caspase-8 expression. Dox induced caspase-3, -7, -8 and -9 and Bid cleavage in S-type cells and death was blocked by caspase inhibitors but not by oxygen radical scavenger BHA. In contrast, dox-induced death in N-type cells was caspase-independent and was inhibited by BHA. Dox induced a drop in mitochondrial membrane permeability in all cell lines. Dox-induced death in S-type cells gave rise to apoptotic nuclei, whereas in N-type cells nuclei were non-apoptotic in morphology. Transfection of SH-EP cells with a dominant negative FADD mutant inhibited TRAIL-induced death, but had no effect on dox-induced apoptosis. These results suggest that S-type cells undergo apoptosis after dox treatment independently of death receptors, whereas N-type cells are killed by a caspase-independent mechanism.

Authors+Show Affiliations

Department of Pediatric Onco-Hematology, Centre Hospitalier Universitaire Vaudois, CH1011 Lausanne, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12203125

Citation

Hopkins-Donaldson, Sally, et al. "Doxorubicin-induced Death in Neuroblastoma Does Not Involve Death Receptors in S-type Cells and Is Caspase-independent in N-type Cells." Oncogene, vol. 21, no. 39, 2002, pp. 6132-7.
Hopkins-Donaldson S, Yan P, Bourloud KB, et al. Doxorubicin-induced death in neuroblastoma does not involve death receptors in S-type cells and is caspase-independent in N-type cells. Oncogene. 2002;21(39):6132-7.
Hopkins-Donaldson, S., Yan, P., Bourloud, K. B., Muhlethaler, A., Bodmer, J. L., & Gross, N. (2002). Doxorubicin-induced death in neuroblastoma does not involve death receptors in S-type cells and is caspase-independent in N-type cells. Oncogene, 21(39), 6132-7.
Hopkins-Donaldson S, et al. Doxorubicin-induced Death in Neuroblastoma Does Not Involve Death Receptors in S-type Cells and Is Caspase-independent in N-type Cells. Oncogene. 2002 Sep 5;21(39):6132-7. PubMed PMID: 12203125.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Doxorubicin-induced death in neuroblastoma does not involve death receptors in S-type cells and is caspase-independent in N-type cells. AU - Hopkins-Donaldson,Sally, AU - Yan,Pu, AU - Bourloud,Katia Balmas, AU - Muhlethaler,Annick, AU - Bodmer,Jean-Luc, AU - Gross,Nicole, PY - 2002/04/10/received PY - 2002/07/15/revised PY - 2002/07/16/accepted PY - 2002/8/31/pubmed PY - 2002/9/24/medline PY - 2002/8/31/entrez SP - 6132 EP - 7 JF - Oncogene JO - Oncogene VL - 21 IS - 39 N2 - Death induced by doxorubicin (dox) in neuroblastoma (NB) cells was originally thought to occur via the Fas pathway, however since studies suggest that caspase-8 expression is silenced in most high stage NB tumors, it is more probable that dox-induced death occurs via a different mechanism. Caspase-8 silenced N-type invasive NB cell lines LAN-1 and IMR-32 were investigated for their sensitivity to dox, and compared to S-type noninvasive SH-EP NB cells expressing caspase-8. All cell lines had similar sensitivities to dox, independently of caspase-8 expression. Dox induced caspase-3, -7, -8 and -9 and Bid cleavage in S-type cells and death was blocked by caspase inhibitors but not by oxygen radical scavenger BHA. In contrast, dox-induced death in N-type cells was caspase-independent and was inhibited by BHA. Dox induced a drop in mitochondrial membrane permeability in all cell lines. Dox-induced death in S-type cells gave rise to apoptotic nuclei, whereas in N-type cells nuclei were non-apoptotic in morphology. Transfection of SH-EP cells with a dominant negative FADD mutant inhibited TRAIL-induced death, but had no effect on dox-induced apoptosis. These results suggest that S-type cells undergo apoptosis after dox treatment independently of death receptors, whereas N-type cells are killed by a caspase-independent mechanism. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/12203125/Doxorubicin_induced_death_in_neuroblastoma_does_not_involve_death_receptors_in_S_type_cells_and_is_caspase_independent_in_N_type_cells_ L2 - https://doi.org/10.1038/sj.onc.1205879 DB - PRIME DP - Unbound Medicine ER -