It has been shown that dysregulation of IGF-1 signaling is associated with tumor incidence and progression, whereas blockade of the signaling can effectively inhibit carcinogenesis. Although several mechanisms of anticancer activity of quercetin were proposed, molecular targets of quercetin have not been identified yet. Hence, we assessed the effect of quercetin on IGF-1 signaling inhibition in BK5.IGF-1 transgenic (Tg) mice, which over-expresses IGF-1 in the skin epidermis. A quercetin diet (0.02% wt/wt) for 20 weeks remarkably delayed the incidence of skin tumor by 2 weeks and reduced tumor multiplicity by 35% in a 7,12-dimethylbenz(a)anthracene (DMBA)-tetradecanoyl phorbol-13-acetate (TPA) two stage mouse skin carcinogenesis protocol. Moreover, skin hyperplasia in Tg mice was significantly inhibited by a quercetin supplementation. Further analysis of the MT1/2 skin papilloma cell line showed that a quercetin treatment dose dependently suppressed IGF-1 induced phosphorylation of the IGF-1 receptor (IGF-1R), insulin receptor substrate (IRS)-1, Akt and S6K; however, had no effect on the phosphorylation of PTEN. Additionally, the quercetin treatment inhibited IGF-1 stimulated cell proliferation in a dose dependent manner. Taken together, these data suggest that quercetin has a potent anticancer activity through the inhibition of IGF-1 signaling.
Animals ; Anticarcinogenic Agents* ; Cell Line ; Cell Proliferation ; Diet ; Epidermis ; Hyperplasia ; Incidence ; Insulin-Like Growth Factor I ; Mice* ; Papilloma ; Phosphorylation ; Quercetin* ; Receptor, IGF Type 1 ; Receptor, Insulin ; Skin Neoplasms* ; Skin*

BACKGROUND/OBJECTIVE: The incidence of colorectal cancer (CRC) has been attributed to higher intake of fat and protein. However, reports on the relationship between protein intake and CRC are inconsistent, possibly due to the complexity of diet composition. In this study, we addressed a question whether alteration of protein intake is independently associated with colonic inflammation and colon carcinogenesis. MATERIALS/METHODS: Balb/c mice were randomly divided into 4 experimental groups: 20% protein (control, 20P, 20% casein/kg diet), 10% protein (10P, 10% casein/kg diet), 30% protein (30P, 30% casein/kg diet), and 50% protein (50P, 50% casein/kg diet) diet groups and were subjected to azoxymethane-dextran sodium sulfate induced colon carcinogenesis. RESULTS: As the protein content of the diet increased, clinical signs of colitis including loss of body weight, rectal bleeding, change in stool consistency, and shortening of the colon were worsened. This was associated with a significant decrease in the survival rate of the mice, an increase in proinflammatory protein expression in the colon, and an increase in mucosal cell proliferation. Further, colon tumor multiplicity was dramatically increased in the 30P (318%) and 50P (438%) groups compared with the control (20P) group. CONCLUSIONS: These results suggest that a high protein diet stimulates colon tumor formation by increasing colonic inflammation and proliferation.
Animals ; Body Weight ; Carcinogenesis* ; Caseins ; Cell Proliferation ; Colitis ; Colon* ; Colonic Neoplasms ; Colorectal Neoplasms ; Diet ; Dietary Proteins* ; Hemorrhage ; Incidence ; Inflammation* ; Mice* ; Sodium ; Survival Rate

Objective: The aim of this study was to investigate the association between blood levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and cognitive impairments among elderly individuals. Methods: Peripheral concentration of TNF-α and IL-6 were measured in all subjects. To assess individual cognitive function, the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Assessment Battery (CERAD-NP) was used, and standardized scores (z-scores) were calculated for each test. Cytokine levels were compared between the diagnostic groups, and correlations between blood inflammatory factor levels and z-scores were analyzed. Results: The 37 participants included 8 patients with Alzheimer’s disease (AD), 15 subjects with mild cognitive impairment (MCI), and 14 cognitively healthy controls. TNF-α and IL-6 levels were higher in patients with AD than in healthy controls. TNF-α levels were higher in the AD group than in the MCI group. However, after adjusting for age, the associations between diagnosis and TNF-α and IL-6 were not significant. The higher the plasma IL-6 level, the lower the z-scores on the Boston Naming Test, Word List Learning, Word List Recognition, and Constructional Recall. The higher the serum TNF-α level, the lower the z-scores on the Word List Learning and Constructional Recall. Negative correlation between serum TNF-α level and the z-score on Word List Learning remained significant when age was adjusted. Conclusion The difference in the blood levels of TNF-α and IL-6 between the diagnostic groups may be associated with aging. However, elevated TNF-α levels were associated with worse immediate memory performance, even after adjusting for age.

Objective: The aim of this study was to investigate the association between blood levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and cognitive impairments among elderly individuals. Methods: Peripheral concentration of TNF-α and IL-6 were measured in all subjects. To assess individual cognitive function, the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Assessment Battery (CERAD-NP) was used, and standardized scores (z-scores) were calculated for each test. Cytokine levels were compared between the diagnostic groups, and correlations between blood inflammatory factor levels and z-scores were analyzed. Results: The 37 participants included 8 patients with Alzheimer’s disease (AD), 15 subjects with mild cognitive impairment (MCI), and 14 cognitively healthy controls. TNF-α and IL-6 levels were higher in patients with AD than in healthy controls. TNF-α levels were higher in the AD group than in the MCI group. However, after adjusting for age, the associations between diagnosis and TNF-α and IL-6 were not significant. The higher the plasma IL-6 level, the lower the z-scores on the Boston Naming Test, Word List Learning, Word List Recognition, and Constructional Recall. The higher the serum TNF-α level, the lower the z-scores on the Word List Learning and Constructional Recall. Negative correlation between serum TNF-α level and the z-score on Word List Learning remained significant when age was adjusted. Conclusion The difference in the blood levels of TNF-α and IL-6 between the diagnostic groups may be associated with aging. However, elevated TNF-α levels were associated with worse immediate memory performance, even after adjusting for age.

Objective: The aim of this study was to investigate the association between blood levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and cognitive impairments among elderly individuals. Methods: Peripheral concentration of TNF-α and IL-6 were measured in all subjects. To assess individual cognitive function, the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Assessment Battery (CERAD-NP) was used, and standardized scores (z-scores) were calculated for each test. Cytokine levels were compared between the diagnostic groups, and correlations between blood inflammatory factor levels and z-scores were analyzed. Results: The 37 participants included 8 patients with Alzheimer’s disease (AD), 15 subjects with mild cognitive impairment (MCI), and 14 cognitively healthy controls. TNF-α and IL-6 levels were higher in patients with AD than in healthy controls. TNF-α levels were higher in the AD group than in the MCI group. However, after adjusting for age, the associations between diagnosis and TNF-α and IL-6 were not significant. The higher the plasma IL-6 level, the lower the z-scores on the Boston Naming Test, Word List Learning, Word List Recognition, and Constructional Recall. The higher the serum TNF-α level, the lower the z-scores on the Word List Learning and Constructional Recall. Negative correlation between serum TNF-α level and the z-score on Word List Learning remained significant when age was adjusted. Conclusion The difference in the blood levels of TNF-α and IL-6 between the diagnostic groups may be associated with aging. However, elevated TNF-α levels were associated with worse immediate memory performance, even after adjusting for age.

Objective: The aim of this study was to investigate the association between blood levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and cognitive impairments among elderly individuals. Methods: Peripheral concentration of TNF-α and IL-6 were measured in all subjects. To assess individual cognitive function, the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Assessment Battery (CERAD-NP) was used, and standardized scores (z-scores) were calculated for each test. Cytokine levels were compared between the diagnostic groups, and correlations between blood inflammatory factor levels and z-scores were analyzed. Results: The 37 participants included 8 patients with Alzheimer’s disease (AD), 15 subjects with mild cognitive impairment (MCI), and 14 cognitively healthy controls. TNF-α and IL-6 levels were higher in patients with AD than in healthy controls. TNF-α levels were higher in the AD group than in the MCI group. However, after adjusting for age, the associations between diagnosis and TNF-α and IL-6 were not significant. The higher the plasma IL-6 level, the lower the z-scores on the Boston Naming Test, Word List Learning, Word List Recognition, and Constructional Recall. The higher the serum TNF-α level, the lower the z-scores on the Word List Learning and Constructional Recall. Negative correlation between serum TNF-α level and the z-score on Word List Learning remained significant when age was adjusted. Conclusion The difference in the blood levels of TNF-α and IL-6 between the diagnostic groups may be associated with aging. However, elevated TNF-α levels were associated with worse immediate memory performance, even after adjusting for age.