Luteolin inhibits matrix metalloproteinase 9 and 2 in azoxymethane-induced colon carcinogenesis

Hum Exp Toxicol. 2014 Nov;33(11):1176-85. doi: 10.1177/0960327114522502. Epub 2014 Feb 14.

Abstract

The present investigation deals with the antimetastatic role of luteolin (LUT) by inhibiting matrix metalloproteinase (MMP)-9 and -2 in azoxymethane (AOM)-induced colon carcinogenesis in Balb/C mice. Animals received AOM at a dosage of 15 mg/kg body weight intraperitoneally once a week for 3 weeks. AOM-induced mice was treated with LUT (1.2 mg of LUT/kg body weight/day orally). After the experimental period, the tumor markers such as γ-glutamyl transferase (GGT), 5' nucleotidase (5'ND), cathepsin-D (Cat-D), and carcinoembroyonic antigen (CEA) were elevated upon induction with AOM. Subsequent treatment with LUT results in the reduction of the tumor markers was recorded. The expressions of MMP-9 and MMP-2 were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence methods. The expressions of MMP-9 and MMP-2 were increased during AOM induction and upon treatment with LUT reduced the expressions. RT-PCR analysis of tissue inhibitor of matrix metalloproteinase (TIMP)-2 was limited during AOM-induced colorectal cancer (CRC). Supplementation of LUT increased the expression of TIMP-2. To conclude, LUT acts as an antimetastatic agent by suppressing MMP-9 and MMP-2 productions and upregulating TIMP-2 expression, thereby suggesting that LUT can be a chemotherapeutic agent against CRC.

Keywords: Azoxymethane; MMP; TIMP-2; colon cancer; luteolin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5'-Nucleotidase / metabolism
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Azoxymethane
  • Biomarkers, Tumor / metabolism
  • Carcinogens
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Luteolin / pharmacology*
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Matrix Metalloproteinase Inhibitors / pharmacology*
  • Mice, Inbred BALB C
  • Tissue Inhibitor of Metalloproteinase-2 / genetics
  • gamma-Glutamyltransferase / metabolism

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Carcinogens
  • Matrix Metalloproteinase Inhibitors
  • Tissue Inhibitor of Metalloproteinase-2
  • gamma-Glutamyltransferase
  • 5'-Nucleotidase
  • Matrix Metalloproteinase 2
  • Mmp2 protein, mouse
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse
  • Luteolin
  • Azoxymethane