Curcumin induces apoptosis-independent death in oesophageal cancer cells.
Affiliation
Leslie C. Quick Laboratory, Cork Cancer Research Centre, BioSciences Institute,, University College Cork and Mercy University Hospital, Cork, Ireland.Issue Date
2012-01-31T16:39:15ZMeSH
Antineoplastic Agents/*pharmacologyApoptosis/*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
Metadata
Show full item recordCitation
Br J Cancer. 2009 Nov 3;101(9):1585-95. Epub 2009 Oct 6.Journal
British journal of cancerDOI
10.1038/sj.bjc.6605308PubMed ID
19809435Abstract
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
engISSN
1532-1827 (Electronic)0007-0920 (Linking)
ae974a485f413a2113503eed53cd6c53
10.1038/sj.bjc.6605308