Location: Jean Mayer Human Nutrition Research Center On Aging
Title: The combination of curcumin and salsalate suppresses high fat diet-induced pro-carcinogenic signaling and colorectal tumorigenesis in azoxymethane-treated miceAuthor
WU, XIAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University | |
KOH, GAR YEE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University | |
CROTT, JIMMY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University | |
MASON, JOEL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University |
Submitted to: Meeting Abstract
Publication Type: Abstract Only Publication Acceptance Date: 3/15/2018 Publication Date: 6/11/2018 Citation: Wu, X., Koh, G., Crott, J.W., Mason, J.B. 2018. The combination of curcumin and salsalate suppresses high fat diet-induced pro-carcinogenic signaling and colorectal tumorigenesis in azoxymethane-treated mice [abstract]. American Society of Nutrition 2018 Meeting. Abstract No. P08-125. Interpretive Summary: Technical Abstract: High fat diets (HFDs) and excessive adiposity elevate pro-inflammatory cytokines and activate signaling pathways that promote colorectal cancer. Previously, we have shown that the combination regimen of curcumin (CUR) and salsalate (SAL) suppresses biochemical inflammation and Akt/NFkappaB signaling in the colons of HFD-fed mice (J Agric Food Chem. 2017; 65:7200-09). Herein, we investigated the suppression of signaling in greater detail, and determined whether this combination prevents the development of neoplastic tumors in the colon. Male A/J mice (n=110) were fed a low-fat diet (LFD, 10% kcal), a HFD (60% kcal), a HFD with CUR (0.4%, wt %), SAL (0.3%, wt %), or a combination of the two agents (CUR/SAL). All mice received 6 injections of azoxymethane (AOM, 10 mg/kg), a colon-specific carcinogen. The HFD mice developed 31% greater fat mass than the LFD mice (p<0.05). Colonic concentrations of IL-6 and IL-1beta were attenuated by the CUR/SAL combination (p<0.02), but not to a significant degree by either agent alone. CUR/SAL significantly suppressed activation of PI3K/Akt/mTOR (p<0.03) and NF-kappaB (p<0.03) pathways, and up-regulated AMPKalpha signaling (p<0.02) in the colonic mucosa. The adiposity generated by the HFD significantly increased tumor multiplicity and tumor burden in the HFD mice, and CUR/SAL also significantly reduced the development of these tumor metrics. Importantly, the combination was more effective than CUR or SAL alone in regard to suppressing tumor multiplicity and Akt/mTOR signaling, and activating AMPKalpha signaling. These observations provide a scientific basis for future clinical trials in obese subjects and/or those on HFDs. |