7-Methoxy-luteolin-8-C-β-6-deoxy-xylo-pyranos-3-uloside exactly (mLU8C-PU) isolated from Arthraxon hispidus inhibits migratory and invasive responses mediated via downregulation of MMP-9 and IL-8 expression in MCF-7 breast cancer cells

Environ Toxicol. 2018 Nov;33(11):1143-1152. doi: 10.1002/tox.22620. Epub 2018 Aug 22.

Abstract

7-Methoxy-luteolin-8-C-β-6-deoxy-xylo-pyranos-3-uloside (mLU8C-PU) is a glycosylflavone of luteolin isolated from Arthraxon hispidus (Thunb.). Luteolin is known to exert anti-migratory and anti-invasive effects on tumor cells. However, there are no reports on the effects of mLU8C-PU on tumor invasiveness and associated signaling pathways. In this study, we demonstrated the anti-migratory and anti-invasive effects of mLU8C-PU in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MCF-7 breast cancer cells. We also investigated the effect of mLU8C-PU on invasion- related signal transducers, including protein kinase Cα (PKCα), c-Jun N terminal kinase (JNK), activator protein-1 (AP-1), and nuclear factor-kappa B (NF-ĸB). TPA-induced membrane translocation of PKCα, phosphorylation of JNK, and the nuclear translocations of AP-1 and NF-κB were downregulated by mLU8C-PU in MCF-7 cells. In addition, mLU8C-PU also inhibited matrix metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8) expression. These results indicate that mLU8C-PU inhibits migratory and invasive responses in MCF-7 breast cancer cells by suppressing MMP-9 and IL-8 expression through mitigating TPA-induced PKCα, JNK activation, and the nuclear translocation of AP-1 and NF-κB. These results suggest that mLU8C-PU may be used as an anti-metastatic agent.

Keywords: Arthraxon hispidus; IL-8; JNK; MMP-9; invasion.

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Adhesion / drug effects*
  • Cell Adhesion / genetics
  • Cell Movement / drug effects*
  • Cell Movement / genetics
  • Down-Regulation / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Luteolin / chemistry
  • Luteolin / isolation & purification
  • Luteolin / pharmacology*
  • MCF-7 Cells
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Invasiveness
  • Phosphorylation / drug effects
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Poaceae / chemistry*
  • Protein Kinase C-alpha / genetics
  • Protein Kinase C-alpha / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics

Substances

  • Antineoplastic Agents, Phytogenic
  • CXCL8 protein, human
  • Interleukin-8
  • Plant Extracts
  • PRKCA protein, human
  • Protein Kinase C-alpha
  • Matrix Metalloproteinase 9
  • Luteolin

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