Visit our Expo - Redox and Inflammation signaling 2012

Session XVI : Chemopreventive agents Poster XVI, 2
In vivo effects of the chemopreventive agent curcumin in the 5T33MM myeloma model.
Jo Caers, Els Van Valckenborgh, Benjamin Van Camp, Karin Vanderkerken.
Laboratory of hematology & immunology. Vrije Universiteit Brussel, Brussels, Belgium
Multiple Myeloma (MM) is a plasma cell malignancy characterised by the accumulation of
monoclonal plasma cells in the bone marrow. The disease is usually preceded by an agedependent
pre-malignant condition called monoclonal gammopathy of undetermined
significance (MGUS). Since these MGUS patients are observed off therapy, we believe that
these patients might benefit from a preventive treatment. In this study, we wanted to
investigate the effects of such a chemopreventive agent, namely curcumin, on MM disease
progression by using the murine 5T33MM myeloma model. In vitro, cell proliferation was
assessed by 3H thymidine uptake. The IC50 for curcumin was about 7,5 µM. Compared to
dexamethasone, a classic drug in MM therapy, curcumin was 50 times more effective. After
overnight, curcumin increased the apoptosis rate of myeloma cells about twofold. In addition,
an inihibitory effect could be seen on neo-vascularisation using a rat aortic ring assay with a
reduction in total number, length and branching of newly created vessels by curcumin
treatment. In vivo analysis of tumor burden was analyzed by injecting two groups of 10 mice
with 5T33MM cells, one group of 10 naive mice was included as negative control. Intraperitoneal
treatment with curcumin (50 mg/kg) was started two days before tumor
inoculation. At week 3, when the vehicle controls showed signs of morbidity, the mice were
sacrificed and tumor load was analyzed by determining bone marrow invasion, liver and
spleen mass and serum paraprotein concentrations. In treated mice, a 47 % reduction in serum
paraprotein concentrations and a 30% reduction in the percentage of 5T33MM idiotype
positive cells in the BM were monitored. Treatment further reduced the splenomegaly by 42%
and the hepatomegaly with 30 %. In conclusion, these are the first in vivo data on the effects
of curcumin on myeloma development. In human myeloma disease, curcumin was earlier
described as inhibitor of NF-kappa b and the JAK-STAT pathway. The inhibitory effects of
curcumin on these pathways will be further assessed on murine 5T33MM cells.
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