Curcumin induces apoptosis-independent death in oesophageal cancer cells.

Hdl Handle:
http://hdl.handle.net/10147/206267
Title:
Curcumin induces apoptosis-independent death in oesophageal cancer cells.
Authors:
O'Sullivan-Coyne, G; O'Sullivan, G C; O'Donovan, T R; Piwocka, K; McKenna, S L
Affiliation:
Leslie C. Quick Laboratory, Cork Cancer Research Centre, BioSciences Institute,, University College Cork and Mercy University Hospital, Cork, Ireland.
Citation:
Br J Cancer. 2009 Nov 3;101(9):1585-95. Epub 2009 Oct 6.
Journal:
British journal of cancer
Issue Date:
31-Jan-2012
URI:
http://hdl.handle.net/10147/206267
DOI:
10.1038/sj.bjc.6605308
PubMed ID:
19809435
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.
Language:
eng
MeSH:
Antineoplastic Agents/*pharmacology; Apoptosis/*drug effects; Autophagy/drug effects; Caspase 3/metabolism; Cell Cycle/drug effects; Cell Line, Tumor; Cell Survival/drug effects; Curcumin/*pharmacology; Cyclin B/metabolism; Cyclin B1; Esophageal Neoplasms/*drug therapy/pathology; Humans; Mitotic Index; Proteasome Endopeptidase Complex/physiology; Ubiquitin/metabolism
ISSN:
1532-1827 (Electronic); 0007-0920 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorO'Sullivan-Coyne, Gen_GB
dc.contributor.authorO'Sullivan, G Cen_GB
dc.contributor.authorO'Donovan, T Ren_GB
dc.contributor.authorPiwocka, Ken_GB
dc.contributor.authorMcKenna, S Len_GB
dc.date.accessioned2012-01-31T16:39:15Z-
dc.date.available2012-01-31T16:39:15Z-
dc.date.issued2012-01-31T16:39:15Z-
dc.identifier.citationBr J Cancer. 2009 Nov 3;101(9):1585-95. Epub 2009 Oct 6.en_GB
dc.identifier.issn1532-1827 (Electronic)en_GB
dc.identifier.issn0007-0920 (Linking)en_GB
dc.identifier.pmid19809435en_GB
dc.identifier.doi10.1038/sj.bjc.6605308en_GB
dc.identifier.urihttp://hdl.handle.net/10147/206267-
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.en_GB
dc.language.isoengen_GB
dc.subject.meshAntineoplastic Agents/*pharmacologyen_GB
dc.subject.meshApoptosis/*drug effectsen_GB
dc.subject.meshAutophagy/drug effectsen_GB
dc.subject.meshCaspase 3/metabolismen_GB
dc.subject.meshCell Cycle/drug effectsen_GB
dc.subject.meshCell Line, Tumoren_GB
dc.subject.meshCell Survival/drug effectsen_GB
dc.subject.meshCurcumin/*pharmacologyen_GB
dc.subject.meshCyclin B/metabolismen_GB
dc.subject.meshCyclin B1en_GB
dc.subject.meshEsophageal Neoplasms/*drug therapy/pathologyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMitotic Indexen_GB
dc.subject.meshProteasome Endopeptidase Complex/physiologyen_GB
dc.subject.meshUbiquitin/metabolismen_GB
dc.titleCurcumin induces apoptosis-independent death in oesophageal cancer cells.en_GB
dc.contributor.departmentLeslie C. Quick Laboratory, Cork Cancer Research Centre, BioSciences Institute,, University College Cork and Mercy University Hospital, Cork, Ireland.en_GB
dc.identifier.journalBritish journal of canceren_GB
dc.description.provinceMunster-
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