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. 2011 Mar 1;11(5):464-73.
doi: 10.4161/cbt.11.5.14410. Epub 2011 Mar 1.

A Polymeric Nanoparticle Formulation of Curcumin Inhibits Growth, Clonogenicity and Stem-Like Fraction in Malignant Brain Tumors

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Free PMC article

A Polymeric Nanoparticle Formulation of Curcumin Inhibits Growth, Clonogenicity and Stem-Like Fraction in Malignant Brain Tumors

Kah Jing Lim et al. Cancer Biol Ther. .
Free PMC article

Abstract

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. Down-regulation 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.

Figures

Figure 1
Figure 1
Growth of brain tumor cell lines is selectively inhibited by nanocurcumin via programmed cell death and cell cycle arrest. MTS assays performed on brain tumor cell lines DAOY (A), D283Med (B), U87 (D), JHH-GBM14 (E) and HSR-GBM1 (F) showed significant growth reduction after treatment over the period of time indicated. This was due to both apoptotic induction (G–I) and G2/M cell cycle arrest (J–L). However, the non-neoplastic NIH-3T3 line instead showed greater growth after nanocurcumin treatment (C). Statistical significance was calculated using the final time points in (A–F). *p < 0.05, **p < 0.01, ***p < 0.001 compared to vehicle.
Figure 2
Figure 2
Curcumin reduces clonogenicity of brain tumor cell lines DAOY (A), D283Med (B), U87 (C) and HSR-GBM1 (D) in a dose-dependent fashion. Equal number of cells were seeded and treated with the indicated nanocurcumin concentrations or void NVA622 nanoparticles (vehicle). Curcumin reduces the CD133-positive stem-like fraction in glioblastoma cell lines JHH-GBM14 (E) and HSR-GBM1, as well as D283Med medulloblastoma cell line (F). JHH-GBM14 (E) and HSR-GBM1 (F) cells were treated with void NVA622 nanoparticle (vehicle), 5, 10 or 20 µM nanocurcumin for 2 days and collected for flow cytometry analysis with CD133 antibodies. DAOY and D283Med (F) cells were treated with the same doses for only 1 day. *p < 0.05, **p < 0.01, ****p < 0.0001 compared to vehicle control.
Figure 3
Figure 3
The IGF-1R pathway is attenuated after nanocurcumin treatment in medulloblastoma cells. DAOY (A) cells treated with the indicated concentrations of curcumin showed decreased transcript levels of IGF-1, IGF-2 and IGF-1R. *p < 0.05, **p < 0.01, ***p < 0.001 compared to vehicle control. Lysates from DAOY (B) cells treated for 26 hours with vehicle or the indicated nanocurcumin concentrations show reduction in p-IGF-1Rβ (Tyr 1135/1136) and IGF-1Rβ protein levels. (C) p-STAT3 (Tyr 705) levels were reduced following curcumin nanoparticle treatment in DAOY cells. Normalized intensities measured by densitometry of two independent experiments are depicted as bar graphs (B and C, right graphs).
Figure 4
Figure 4
The Hh pathway is downregulated after curcumin treatment. Transcript levels of Hh pathway targets (Gli1 and Ptch1B) are reduced following treatment with nanocurcumin in DAOY (A) cells, but not in D283Med (B) or HSR-GBM1 (C). Protein levels of Bcl2 are downregulated following nanocurcumin treatment in DAOY cells (D). *p < 0.05, ***p < 0.001 compared to vehicle.

Comment in

  • Indian gold treating cancer in the age of nano.
    Tuttle S, Hertan L, Katz JS. Tuttle S, et al. Cancer Biol Ther. 2011 Mar 1;11(5):474-6. doi: 10.4161/cbt.11.5.14810. Epub 2011 Mar 1. Cancer Biol Ther. 2011. PMID: 21263231 No abstract available.

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