Magnolol suppresses metastasis via inhibition of invasion, migration, and matrix metalloproteinase-2/-9 activities in PC-3 human prostate carcinoma cells

Biosci Biotechnol Biochem. 2010;74(5):961-7. doi: 10.1271/bbb.90785. Epub 2010 May 7.

Abstract

Magnolol, a hydroxylated biphenyl compound isolated from the root and stem bark of Magnolia officinalis, has been reported to have anticancer activity, but little is known about its molecular mechanisms of action. Increased expression of cyclooxygenase-2 (COX-2), a key enzyme in arachidonic acid metabolism, has been identified in many cancer types. Matrix metalloproteinases (MMPs) are enzymes involved in various steps of metastasis development. The objective of this study was to study the effects of magnolol on cancer invasion and metastasis using PC-3 human prostate carcinoma cells. Cellular proliferation was determined by MTT colorimetric assay. Magnolol inhibited cell growth in a dose-dependent manner. In an invasion assay conducted in Transwell chambers, magnolol showed 33 and 98% inhibition of cancer cell at 10 microM and 20 microM concentrations, respectively, compared to the control. The expression of MMP-2/-9 and COX-1/-2 was assessed by gelatin zymography and Western blot respectively. The protein and mRNA levels of both MMP-2 and MMP-9 were down-regulated by magnolol treatment in a dose-dependent manner. These results demonstrate the antimetastatic properties of magnolol in inhibiting the adhesion, invasion, and migration of PC-3 human prostate cancer cells.

MeSH terms

  • Biphenyl Compounds / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Cyclooxygenase 1 / genetics
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Down-Regulation / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lignans / pharmacology*
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase Inhibitors*
  • Neoplasm Invasiveness / prevention & control
  • Neoplasm Metastasis / prevention & control
  • Prostatic Neoplasms / enzymology*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology*

Substances

  • Biphenyl Compounds
  • Lignans
  • Matrix Metalloproteinase Inhibitors
  • magnolol
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9