Induction of apoptosis and reduction of MMP gene expression in the U373 cell line by polyphenolics in Aronia melanocarpa and by curcumin

Oncol Rep. 2012 Oct;28(4):1435-42. doi: 10.3892/or.2012.1941. Epub 2012 Jul 27.


Malignant brain tumours are rare but are the most challenging types of cancers to treat. Despite conventional multimodality approaches available for their management, the outlook for most patients remains dismal due to the ability of the tumour cells to invade the normal brain. Attention has now focused on novel therapeutic interventions such as as the use of micronutrients. Both chokeberry extract (Aronia melanocarpa), which is rich in natural pigments such as anthocyanins and curcumin (diferuloylmethane) found in turmeric (Curcuma longa) have been reported to possess anticancer properties in other cancers. The aim of this study was to extend our previous research to evaluate the therapeutic potential of these two agents by testing their ability to induce apoptosis in an established glioblastoma cell line (U373). This was accomplished by treating the cells for 48 h with either chokeberry extract or curcumin, and using the Annexin-V assay. Gene profiles of 8 MMPs (2, 9, 14, 15, 16, 17, 24 and 25) and 4 TIMPs (1, 2, 3 and 4) were analysed for effects of mediators of invasion by quantitative real-time polymerase chain reaction (RT-PCR). The IC50 values determined for curcumin and chokeberry extract were 15 and 200 µg/ml, respectively. Our results also suggest that curcumin induces apoptosis but chokeberry extract is necrotic to this cell line. It is possible that chokeberry extract kills the cells by other non-apoptotic pathways. In addition, the RT-PCR results show downregulation of the gene expression of MMP-2, -14, -16 and -17 for both micronutrients. Taken together, the comparative data suggest that both curcumin and chokeberry extract may exhibit their anticancer potential by inducing apoptosis and inhibiting invasion by reducing MMP gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Cell Death / drug effects
  • Cell Line, Tumor / drug effects
  • Curcumin / pharmacology*
  • Drug Screening Assays, Antitumor
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioblastoma / drug therapy
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Humans
  • Inhibitory Concentration 50
  • Matrix Metalloproteinase 14 / genetics
  • Matrix Metalloproteinase 16 / genetics
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinases, Membrane-Associated / genetics
  • Matrix Metalloproteinases, Secreted / genetics*
  • Photinia / chemistry*
  • Plant Extracts / pharmacology
  • Polyphenols / pharmacology*


  • Antineoplastic Agents, Phytogenic
  • Plant Extracts
  • Polyphenols
  • MMP17 protein, human
  • Matrix Metalloproteinase 16
  • Matrix Metalloproteinases, Membrane-Associated
  • Matrix Metalloproteinases, Secreted
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 14
  • Curcumin