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

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

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.

MeSH terms

  • AC133 Antigen
  • Antigens, CD / drug effects
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Curcumin / administration & dosage
  • Curcumin / chemistry
  • Curcumin / pharmacology*
  • Down-Regulation / drug effects
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Glycoproteins / drug effects
  • Hedgehog Proteins / analysis
  • Hedgehog Proteins / genetics
  • Humans
  • Medulloblastoma / drug therapy*
  • Medulloblastoma / metabolism
  • Medulloblastoma / pathology
  • Mitosis / drug effects
  • Nanocapsules*
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / physiology
  • Peptides / drug effects
  • Polymers
  • Receptors, Notch / analysis
  • Receptors, Notch / genetics
  • STAT3 Transcription Factor / analysis
  • Signal Transduction / drug effects
  • Somatomedins / genetics
  • Tumor Stem Cell Assay

Substances

  • AC133 Antigen
  • Antigens, CD
  • Antineoplastic Agents
  • Glycoproteins
  • Hedgehog Proteins
  • Nanocapsules
  • PROM1 protein, human
  • Peptides
  • Polymers
  • Receptors, Notch
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Somatomedins
  • Curcumin