Modulatory effect of hesperidin on benzo(a)pyrene induced experimental lung carcinogenesis with reference to COX-2, MMP-2 and MMP-9

Eur J Pharmacol. 2010 Dec 15;649(1-3):320-7. doi: 10.1016/j.ejphar.2010.09.017. Epub 2010 Sep 29.

Abstract

Hesperidin is a naturally occurring flavonoid that has been reported to possess anticancer effects. The purpose of this study is to evaluate the effect of hesperidin in modulating the expressions of cyclooxygenase-2 (COX-2), mast cells (MCs) and matrix metalloproteinases (MMPs) during benzo(a)pyrene (B(a)P) induced lung carcinogenesis in mice. B(a)P (50 mg/kg body weight) induced animals showed increased mast cell density (MCD) as revealed by toluidine blue staining and severe expression of COX-2 along with upregulated expression of MMP-2 and MMP-9 as revealed by Western blotting and immunohistochemistry. Supplementation of hesperidin (25 mg/kg body weight) to lung cancer bearing mice attenuated MCD and downregulated the expressions of COX-2, MMP-2 and MMP-9. These observations show that hesperidin exerts its anti-carcinogenic activity against lung cancer by altering the expressions of COX-2, MMP-2 and MMP-9.

MeSH terms

  • Animals
  • Anticarcinogenic Agents / adverse effects
  • Anticarcinogenic Agents / therapeutic use*
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Benzo(a)pyrene / toxicity
  • Blotting, Western
  • Carcinogens / toxicity
  • Cell Count
  • Cyclooxygenase 2 / metabolism*
  • Dietary Supplements
  • Down-Regulation / drug effects
  • Hesperidin / adverse effects
  • Hesperidin / therapeutic use*
  • Immunohistochemistry
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / prevention & control*
  • Male
  • Mast Cells / drug effects
  • Mast Cells / pathology
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinases, Secreted / metabolism*
  • Mice

Substances

  • Anticarcinogenic Agents
  • Antineoplastic Agents, Phytogenic
  • Carcinogens
  • Benzo(a)pyrene
  • Hesperidin
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Matrix Metalloproteinases, Secreted
  • Matrix Metalloproteinase 2
  • Mmp2 protein, mouse
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse