"Dietary Linoleic Acid and Glucose Enhances Azoxymethane-Induced Colon Cancer and Metastases..."

"...via the Expression of High-Mobility Group Box 1" (PDF)

" Colorectal cancer (CRC) is the third leading cause of cancer in the Japanese population  [1].  With the increasing Western influence on the diet of the Japanese people, the frequency of CRC has been continuously increasing  [2] . In particular, the increase in dietary fat intake is considered to be a relevant factor for the increase in CRC. The effects of a high-fat diet on the predisposition to CRC depend on the source of oils. Dietary oils such as corn oil contain high amounts of linoleic acid (LA). The effects of this acid in synergy with azoxymethane (AOM) on rat colon mucosa were investigated...

"...As shown in table 1 , in the rats belonging to group L+G, body weight and calorie intake were increased (24 and 67%) 50 weeks after the AOM injection....

"...These pathways function to bring about accelerated growth and migration of cancer cells, and they suppress apoptosis, all of which contribute to the metastatic potential of cancer cells [17, 18, 22] .

"We showed that HMGB1 protein levels in the colonic mucosa and tumors were significantly increased in the rats belonging to groups L+G [Linoleic acid + Glucose], L [Linoleic acid] and G [Glucose] compared to that in the rats belonging to group C [Control]. In addition, the HMGB1 levels were correlated with cancer multiplicity. Lymph node metastases were more frequently detected in the rats of group L+G than in those of group L. Moreover, the rats of groups G and C did not exhibit nodal metastases. Thus, the concurrent increase in HMGB1 levels in the rats of group L+G at week 70 might be associated with lymph node metastases. We confirmed the higher RAGE expression in colon mucosa and carcinomas in group L+G compared with groups C, L, or G (data not shown). The highest levels of HMGB1 in tumors were detected in all the 6 rats that exhibited nodal metastases in groups L+G and L. [Emphasis mine] In human cancers, RAGE and HMGB1 expression is significantly higher in metastatic than in non-metastatic gastric and colorectal cancers [18, 19] ....

"...In the present study, the high-LA and high-glucose drink diet exhibited significant synergic effects on cancer multiplicity, metastases and upregulation of HMGB1. These two dietary factors are also strongly associated with the metabolic syndrome. The dietary control of these factors might be essential for CRC prevention...."