Oral administration of apigenin inhibits metastasis through AKT/P70S6K1/MMP-9 pathway in orthotopic ovarian tumor model

Int J Mol Sci. 2012;13(6):7271-82. doi: 10.3390/ijms13067271. Epub 2012 Jun 13.

Abstract

Apigenin, a flavonoid commonly present in the daily diet, is known for its potential anti-tumor properties. However, the effect of apigenin via oral administration on tumor growth and metastasis remains unknown. In this study we developed an orthotopic ovarian tumor model in nude mice to test the effect of apigenin oral administration, and showed that apigenin inhibited the micrometastasis of cancer cells in the animal tumor model. To understand the mechanism of apigenin in inhibiting metastasis, we found that apigenin greatly inhibited MMP-9 expression and p-AKT and p-p70S6K1 levels in the tumor tissues compared to the control group. We further demonstrated that the downregulation of MMP-9 by apigenin was mediated by the AKT/p70S6K1 pathway. These findings help to address the question with common interests to the public of whether oral uptake of flavonoids is effective in preventing cancer. Our results demonstrate for the first time that oral uptake of apigenin can inhibit tumor metastasis through MMP-9 expression using the orthotopic ovarian tumor model.

Keywords: MMP-9; apigenin; metastasis; orthotopic ovarian cancer model.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Apigenin / pharmacology*
  • Cell Line, Tumor
  • Female
  • Matrix Metalloproteinase 9 / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism*
  • Signal Transduction / drug effects*

Substances

  • Apigenin
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases, 70-kDa
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse