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


CONCLUSIONS
These data suggest that dietary LA and glucose provided the synergistic effect on AOM-induced rat colon cancer through HMGB1 induction.
Ohmori
Hitoshi
H
Department of Molecular Pathology, Nara Medical University, Kashihara, Japan.
Luo
Yi
Y
Fujii
Kiyomu
K
Sasahira
Tomonori
T
Shimomoto
Takasumi
T
Denda
Ayumi
A
Kuniyasu
Hiroki
H
D000818:Animals; D001397:Azoxymethane / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D004032:Diet; D004357:Drug Synergism; D005947:Glucose / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D024243:HMGB1 Protein / Q000009:adverse effects / Q000378:metabolism* / Q000494:pharmacology; D019787:Linoleic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D024243:HMGB1 Protein; D019787:Linoleic Acid; D005947:Glucose; D001397:Azoxymethane