A polymeric nanoparticle formulation of curcumin inhibits growth, clonogenicity and stem-like fraction in malignant brain tumors

被引:187
作者
Lim, Kah Jing [1 ,2 ]
Bisht, Savita [1 ]
Bar, Eli E. [1 ]
Maitra, Anirban [1 ,3 ]
Eberhart, Charles G. [1 ,3 ,4 ]
机构
[1] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Grad Program Pathobiol, Baltimore, MD USA
[3] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA
[4] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA
关键词
curcumin; hedgehog; IGF; glioblastoma; medulloblastoma; nanocurcumin; nanoCurc (TM); NF-KAPPA-B; FACTOR-I; NEURAL PROGENITORS; GLIOBLASTOMA CELLS; INSULIN; MEDULLOBLASTOMA; PATHWAY; ACTIVATION; EXPRESSION; APOPTOSIS;
D O I
10.4161/cbt.11.5.14410
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Curcumin is a polyphenolic compound derived from the Indian spice turmeric. We used nanoparticle-encapsulated curcumin to treat medulloblastoma and glioblastoma cells. This formulation caused a dose-dependent decrease in growth of multiple brain tumor cell cultures, including the embryonal tumor derived lines DAOY and D283Med, and the glioblastoma neurosphere lines HSR-GBM1 and JHH-GBM14. The reductions in viable cell mass observed were associated with a combination of G(2)/M arrest and apoptotic induction. Curcumin also significantly decreased anchorage-independent clonogenic growth and reduced the CD133-positive stem-like population. Downregulation of the insulin-like growth factor pathway in DAOY medulloblastoma cells was observed, providing one possible mechanism for the changes. Levels of STAT3 were also attenuated. Hedgehog signaling was blocked in DAOY cells but Notch signaling was not inhibited. Our data suggest that curcumin nanoparticles can inhibit malignant brain tumor growth through the modulation of cell proliferation, survival and stem cell phenotype.
引用
收藏
页码:464 / 473
页数:10
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