Quercetin suppresses the proliferation of multiple myeloma cells by down-regulating IQ motif-containing GTPase activating protein 1 expression and extracellular signal-regulated kinase activation

Leuk Lymphoma. 2014 Nov;55(11):2597-604. doi: 10.3109/10428194.2013.879128. Epub 2014 Mar 7.

Abstract

The flavonoid quercetin has shown anti-tumor effects against a variety of solid tumors. However, its effects on multiple myeloma (MM) remain unclear. In this study we examined the proliferation of human myeloma cell lines U266, KM3 and RPMI8226 and MM derived cells from four patients with MM after quercetin treatment, and detected the expression of IQ motif-containing GTPase activating protein 1 (IQGAP1), a scaffold protein involved in mitogen-activated protein kinase (MAPK) signaling, by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. We found that quercetin inhibited the proliferation of MM cells in a dose- and time-dependent manner, accompanied by reduced IQGAP1 expression at mRNA and protein levels, and reduced extracellular signal-regulated kinase 1/2 (ERK1/2) activation. Furthermore, we found that quercetin inhibited the interaction between IQGAP1 and ERK1/2 in RPMI8226 cells. In summary, our results suggest that quercetin suppresses the proliferation of MM cells by down-regulating IQGAP1 expression and ERK activation, and has potential as a novel agent to target oncogenic kinase cascades for MM therapy.

Keywords: IQ motif-containing GTPase activating protein 1; MAP kinase pathway; Quercetin; multiple myeloma.

MeSH terms

  • Aged
  • Antioxidants / pharmacology
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Multiple Myeloma / genetics
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology
  • Protein Binding / drug effects
  • Quercetin / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Tumor Cells, Cultured
  • ras GTPase-Activating Proteins / genetics
  • ras GTPase-Activating Proteins / metabolism*

Substances

  • Antioxidants
  • IQ motif containing GTPase activating protein 1
  • ras GTPase-Activating Proteins
  • Quercetin
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3