Curcumin induces apoptosis-independent death in oesophageal cancer cells.

Hdl Handle:
http://hdl.handle.net/10147/84975
Title:
Curcumin induces apoptosis-independent death in oesophageal cancer cells.
Authors:
O'Sullivan-Coyne, G; O'Sullivan, GC; O'Donovan, TR; Piwocka, K; McKenna, SL
Affiliation:
Leslie C. Quick Laboratory, Cork Cancer Research Centre, BioSciences Institute, University College Cork and Mercy University Hospital, Cork, Ireland.
Citation:
Curcumin induces apoptosis-independent death in oesophageal cancer cells. 2009: Br. J. Cancer
Journal:
British journal of cancer
Issue Date:
6-Oct-2009
URI:
http://hdl.handle.net/10147/84975
DOI:
10.1038/sj.bjc.6605308
PubMed ID:
19809435
Additional Links:
http://search.ebscohost.com/
Abstract:
Background:Oesophageal cancer incidence is increasing and survival rates remain extremely poor. Natural agents with potential for chemoprevention include the phytochemical curcumin (diferuloylmethane). We have examined the effects of curcumin on a panel of oesophageal cancer cell lines.Methods:MTT (3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyl tetrazolium bromide) assays and propidium iodide staining were used to assess viability and DNA content, respectively. Mitotic catastrophe (MC), apoptosis and autophagy were defined by both morphological criteria and markers such as MPM-2, caspase 3 cleavage and monodansylcadaverine (MDC) staining. Cyclin B and poly-ubiquitinated proteins were assessed by western blotting.Results:Curcumin treatment reduces viability of all cell lines within 24 h of treatment in a 5-50 muM range. Cytotoxicity is associated with accumulation in G2/M cell-cycle phases and distinct chromatin morphology, consistent with MC. Caspase-3 activation was detected in two out of four cell lines, but was a minor event. The addition of a caspase inhibitor zVAD had a marginal or no effect on cell viability, indicating predominance of a non-apoptotic form of cell death. In two cell lines, features of both MC and autophagy were apparent. Curcumin-responsive cells were found to accumulate poly-ubiquitinated proteins and cyclin B, consistent with a disturbance of the ubiquitin-proteasome system. This effect on a key cell-cycle checkpoint regulator may be responsible for the mitotic disturbances and consequent cytotoxicity of this drug.Conclusion:Curcumin can induce cell death by a mechanism that is not reliant on apoptosis induction, and thus represents a promising anticancer agent for prevention and treatment of oesophageal cancer.British Journal of Cancer advance online publication, 6 October 2009; doi:10.1038/sj.bjc.6605308 www.bjcancer.com.
Item Type:
Article
ISSN:
1532-1827

Full metadata record

DC FieldValue Language
dc.contributor.authorO'Sullivan-Coyne, Gen
dc.contributor.authorO'Sullivan, GCen
dc.contributor.authorO'Donovan, TRen
dc.contributor.authorPiwocka, Ken
dc.contributor.authorMcKenna, SLen
dc.date.accessioned2009-10-28T11:46:42Z-
dc.date.available2009-10-28T11:46:42Z-
dc.date.issued2009-10-06-
dc.identifier.citationCurcumin induces apoptosis-independent death in oesophageal cancer cells. 2009: Br. J. Canceren
dc.identifier.issn1532-1827-
dc.identifier.pmid19809435-
dc.identifier.doi10.1038/sj.bjc.6605308-
dc.identifier.urihttp://hdl.handle.net/10147/84975-
dc.description.abstractBackground:Oesophageal cancer incidence is increasing and survival rates remain extremely poor. Natural agents with potential for chemoprevention include the phytochemical curcumin (diferuloylmethane). We have examined the effects of curcumin on a panel of oesophageal cancer cell lines.Methods:MTT (3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyl tetrazolium bromide) assays and propidium iodide staining were used to assess viability and DNA content, respectively. Mitotic catastrophe (MC), apoptosis and autophagy were defined by both morphological criteria and markers such as MPM-2, caspase 3 cleavage and monodansylcadaverine (MDC) staining. Cyclin B and poly-ubiquitinated proteins were assessed by western blotting.Results:Curcumin treatment reduces viability of all cell lines within 24 h of treatment in a 5-50 muM range. Cytotoxicity is associated with accumulation in G2/M cell-cycle phases and distinct chromatin morphology, consistent with MC. Caspase-3 activation was detected in two out of four cell lines, but was a minor event. The addition of a caspase inhibitor zVAD had a marginal or no effect on cell viability, indicating predominance of a non-apoptotic form of cell death. In two cell lines, features of both MC and autophagy were apparent. Curcumin-responsive cells were found to accumulate poly-ubiquitinated proteins and cyclin B, consistent with a disturbance of the ubiquitin-proteasome system. This effect on a key cell-cycle checkpoint regulator may be responsible for the mitotic disturbances and consequent cytotoxicity of this drug.Conclusion:Curcumin can induce cell death by a mechanism that is not reliant on apoptosis induction, and thus represents a promising anticancer agent for prevention and treatment of oesophageal cancer.British Journal of Cancer advance online publication, 6 October 2009; doi:10.1038/sj.bjc.6605308 www.bjcancer.com.-
dc.languageENG-
dc.relation.urlhttp://search.ebscohost.com/en
dc.titleCurcumin induces apoptosis-independent death in oesophageal cancer cells.en
dc.typeArticleen
dc.contributor.departmentLeslie C. Quick Laboratory, Cork Cancer Research Centre, BioSciences Institute, University College Cork and Mercy University Hospital, Cork, Ireland.en
dc.identifier.journalBritish journal of canceren
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