Dietary linoleic acid and glucose enhances azoxymethane-induced colon cancer and metastases via the expression of high-mobility group box 1

Pathobiology. 2010;77(4):210-7. doi: 10.1159/000296305. Epub 2010 Jul 7.

Abstract

Objective: High-mobility group box 1 (HMGB1) was closely associated with progression and metastasis of colorectal cancer.

Methods: We examined the significance of HMGB1 in causing colon carcinogenesis induced by azoxymethane (AOM) injection in Fischer 344 rats fed on a control diet (group C), a 15% linoleic acid (LA) diet (group L), a control diet with 10% glucose drink (group G), and a 15% LA diet with a 10% glucose drink (group L+G).

Results: Group L+G showed the highest body weight and calorie intake. Serum and mucosal HMGB1 levels were temporally increased in all groups, while the highest levels were observed in group L+G. Mucosal HMGB1 levels were correlated with cancer multiplicity and nodal metastases. In the AOM-injected rats fed the 15% LA diet with 10% glucose drink, administration of HMGB1 antibody suppressed serum HMGB1 concentration and cancer multiplicity.

Conclusion: These data suggest that dietary LA and glucose provided the synergistic effect on AOM-induced rat colon cancer through HMGB1 induction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azoxymethane / metabolism
  • Azoxymethane / pharmacology
  • Azoxymethane / toxicity*
  • Carcinogens / toxicity*
  • Colonic Neoplasms / chemically induced*
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Diet
  • Drug Synergism
  • Glucose / adverse effects
  • Glucose / metabolism
  • Glucose / pharmacology
  • HMGB1 Protein / adverse effects
  • HMGB1 Protein / metabolism*
  • HMGB1 Protein / pharmacology
  • Linoleic Acid / administration & dosage
  • Linoleic Acid / adverse effects*
  • Linoleic Acid / metabolism
  • Linoleic Acid / pharmacology
  • Male
  • Random Allocation
  • Rats
  • Rats, Inbred F344

Substances

  • Carcinogens
  • HMGB1 Protein
  • Linoleic Acid
  • Glucose
  • Azoxymethane