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Human melanoma cells selected for resistance to apoptosis by prolonged exposure to tumor necrosis factor-related apoptosis-inducing ligand are more vulnerable to necrotic cell death induced by cisplatin.
Clin Cancer Res. 2006 Feb 15; 12(4):1355-64.CC

Abstract

PURPOSE

Heterogeneous sensitivity of melanoma cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis may lead to outgrowth of TRAIL-resistant cells and limit successful treatment by TRAIL. The present study aims to better understand the biological characteristics of melanoma cells resistant to TRAIL-induced apoptosis.

EXPERIMENTAL DESIGN

We generated TRAIL-resistant melanoma cells by prolonged exposure to TRAIL and characterized the cells in terms of their sensitivity to killing induced by a panel of cytotoxic agents using biological and biochemical methods.

RESULTS

TRAIL-resistant melanoma cells are cross-resistant to apoptosis induced by another death ligand FasL, the DNA-damaging agent cisplatin, the histone deacetylase inhibitor suberic bishydroxamate, and the antimicrotubule Vinca alkaloid, vincristine. The apoptotic signaling seemed to be inhibited upstream of mitochondrial apoptotic events and was associated with decreased expression of multiple apoptotic mediators, including pro-caspase-8, Fas-associated death domain, Bid, Bim, p53, and the products of its proapoptotic target genes. Despite being resistant to apoptosis, TRAIL-resistant melanoma cells were more vulnerable to cisplatin-induced nonapoptotic cell death. This was characterized by lack of DNA fragmentation, delayed externalization of phosphatidylserine, caspase and p53 independence, and severe mitochondrial disruption, and was preceded by poly(ADP)ribose polymerase (PARP) activation and depletion of intracellular ATP, indicative of necrotic cell death. Inhibition of PARP activity partially converted the mode of cell death from necrosis to apoptosis.

CONCLUSIONS

TRAIL-resistant melanoma cells are cross-resistant to apoptosis induced by various apoptotic stimuli but are more sensitive to nonapoptotic cell death induced by cisplatin. Exploration of chemotherapy-induced nonapoptotic cell death may provide an alternative strategy in overcoming resistance of melanoma cells to TRAIL-induced apoptosis.

Authors+Show Affiliations

Immunology and Oncology Unit, Royal Newcastle Hospital, Newcastle, NSW, Australia.No 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

16489094

Citation

Zhang, Xu Dong, et al. "Human Melanoma Cells Selected for Resistance to Apoptosis By Prolonged Exposure to Tumor Necrosis Factor-related Apoptosis-inducing Ligand Are More Vulnerable to Necrotic Cell Death Induced By Cisplatin." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 12, no. 4, 2006, pp. 1355-64.
Zhang XD, Wu JJ, Gillespie S, et al. Human melanoma cells selected for resistance to apoptosis by prolonged exposure to tumor necrosis factor-related apoptosis-inducing ligand are more vulnerable to necrotic cell death induced by cisplatin. Clin Cancer Res. 2006;12(4):1355-64.
Zhang, X. D., Wu, J. J., Gillespie, S., Borrow, J., & Hersey, P. (2006). Human melanoma cells selected for resistance to apoptosis by prolonged exposure to tumor necrosis factor-related apoptosis-inducing ligand are more vulnerable to necrotic cell death induced by cisplatin. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 12(4), 1355-64.
Zhang XD, et al. Human Melanoma Cells Selected for Resistance to Apoptosis By Prolonged Exposure to Tumor Necrosis Factor-related Apoptosis-inducing Ligand Are More Vulnerable to Necrotic Cell Death Induced By Cisplatin. Clin Cancer Res. 2006 Feb 15;12(4):1355-64. PubMed PMID: 16489094.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human melanoma cells selected for resistance to apoptosis by prolonged exposure to tumor necrosis factor-related apoptosis-inducing ligand are more vulnerable to necrotic cell death induced by cisplatin. AU - Zhang,Xu Dong, AU - Wu,Jing Jing, AU - Gillespie,Susan, AU - Borrow,Jodie, AU - Hersey,Peter, PY - 2006/2/21/pubmed PY - 2006/4/18/medline PY - 2006/2/21/entrez SP - 1355 EP - 64 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 12 IS - 4 N2 - PURPOSE: Heterogeneous sensitivity of melanoma cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis may lead to outgrowth of TRAIL-resistant cells and limit successful treatment by TRAIL. The present study aims to better understand the biological characteristics of melanoma cells resistant to TRAIL-induced apoptosis. EXPERIMENTAL DESIGN: We generated TRAIL-resistant melanoma cells by prolonged exposure to TRAIL and characterized the cells in terms of their sensitivity to killing induced by a panel of cytotoxic agents using biological and biochemical methods. RESULTS: TRAIL-resistant melanoma cells are cross-resistant to apoptosis induced by another death ligand FasL, the DNA-damaging agent cisplatin, the histone deacetylase inhibitor suberic bishydroxamate, and the antimicrotubule Vinca alkaloid, vincristine. The apoptotic signaling seemed to be inhibited upstream of mitochondrial apoptotic events and was associated with decreased expression of multiple apoptotic mediators, including pro-caspase-8, Fas-associated death domain, Bid, Bim, p53, and the products of its proapoptotic target genes. Despite being resistant to apoptosis, TRAIL-resistant melanoma cells were more vulnerable to cisplatin-induced nonapoptotic cell death. This was characterized by lack of DNA fragmentation, delayed externalization of phosphatidylserine, caspase and p53 independence, and severe mitochondrial disruption, and was preceded by poly(ADP)ribose polymerase (PARP) activation and depletion of intracellular ATP, indicative of necrotic cell death. Inhibition of PARP activity partially converted the mode of cell death from necrosis to apoptosis. CONCLUSIONS: TRAIL-resistant melanoma cells are cross-resistant to apoptosis induced by various apoptotic stimuli but are more sensitive to nonapoptotic cell death induced by cisplatin. Exploration of chemotherapy-induced nonapoptotic cell death may provide an alternative strategy in overcoming resistance of melanoma cells to TRAIL-induced apoptosis. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/16489094/Human_melanoma_cells_selected_for_resistance_to_apoptosis_by_prolonged_exposure_to_tumor_necrosis_factor_related_apoptosis_inducing_ligand_are_more_vulnerable_to_necrotic_cell_death_induced_by_cisplatin_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=16489094 DB - PRIME DP - Unbound Medicine ER -