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| vauxall... |
 Posted: Thu Oct 29, 2009 4:17 pm |
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http://www.nature.com/bjc/journal/v101/n9/abs/6605308a.html
Curcumin induces apoptosis-independent death in oesophageal cancer
cells
G O'Sullivan-Coyne1, G C O'Sullivan1, T R O'Donovan1, K Piwocka2 and S
L McKenna1
1Leslie C. Quick Laboratory, Cork Cancer Research Centre, BioSciences
Institute, University College Cork and Mercy University Hospital,
Cork, Ireland
2Nencki Institute of Experimental Biology, Warsaw, Poland
Correspondence: Dr SL McKenna Sharon, E-mail: s.mckenna at (no spam) ucc.ie
Received 1 June 2009; Revised 10 August 2009; Accepted 17 August 2009;
Published online 6 October 2009.
Top of pageAbstract
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 M 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. |
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