Curcumin induces apoptosis in human neuroblastoma cells via inhibition of NFkappaB.
BACKGROUND
Metastasised neuroblastoma is a largely incurable neoplasia in children over one year of age using current treatment protocols. After dissemination to the bone, the survival rate is <7%, indicating an urgent need for novel therapeutic regimes. As curcumin (diferuloylmethane) had been shown to exert strong anticancer effects against diverse human malignancies different from neurblastoma, the antiproliferative effect of curcumin on the growth of human neuroblastoma cell lines was tested.


METHODS
Proliferation of neuroblastoma cell lines Lan-5, SK-N-SH and Kelly under the treatment of curcumin over a broad concentration range (1 x 10(-5) to 1 x 10(2) microM) was assessed using XTT cell proliferation assays. Possible induction of apoptosis through curcumin treatment was assessed by detection of DNA fragmentation. To investigate the effect of curcumin on NFkappaB activation, the protein levels of the NFkappaB subunit p65 of curcumin-treated cells were compared to untreated cells using Western blots.


RESULTS
Curcumin showed a significant dose-dependent antiproliferative effect on all three neuroblastoma cell lines starting at a concentration of 1 x 10(-3) microM. The highest concentration of 1 x 10(2) microM significantly reduced the viable cell count to 8-48% depending on the cell line. This antiproliferative effect was mediated through an increased induction of apoptosis by inhibition of NFkappaB, corroborating earlier findings indicating an antiapoptotic effect of NFkappaB.


CONCLUSIONS
Our results suggest that curcumin might hold promise in the treatment of patients suffering from neuroblastoma.
Freudlsperger
Christian
C
Institut für Anatomie II: Experimentelle Morphologie, Universitätsklinikum Hamburg-Eppendorf 20246 Hamburg, Germany. c.freudlsperger@uke.uni-hamburg.de
Greten
Johannes
J
Schumacher
Udo
U
D017209:Apoptosis / Q000187:drug effects*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002675:Child, Preschool; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D007223:Infant; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D016328:NF-kappa B; D003474:Curcumin