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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #351574
Title: Curcumin and salsalate suppresses colonic inflammation and procarcinogenic signaling in high-fat-fed, azoxymethane-treated mice

Author
item WU, XIAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item PFALZER, ANNA - Vanderbilt University
item KOH, GAR YEE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item TANG, SANYUAN - University Of South China
item CROTT, JIMMY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item THOMAS, MICHAEL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item MEYDANI, MOHSEN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item MASON, JOEL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/26/2017
Publication Date: 7/26/2017
Citation: Wu, X., Pfalzer, A.C., Koh, G., Tang, S., Crott, J.W., Thomas, M.J., Meydani, M., Mason, J.B. 2017. Curcumin and salsalate suppresses colonic inflammation and procarcinogenic signaling in high-fat-fed, azoxymethane-treated mice. Journal of Agricultural and Food Chemistry. 65(33):7200-7209. https://doi.org/10.1021/acs.jafc.7b02648.

Interpretive Summary: High-fat diets (HFDs) and obesity increase the degree of inflammation in the colon, altering gene expression in a manner that promotes the development of colorectal cancer (CRC). Thus, compounds that reduce inflammation are potential anti-cancer agents. Curcumin (CUR), a dietary component, and salsalate (SAL), a non-steroidal anti-inflammatory drug, are both anti-inflammatory compounds. We investigated the inhibitory effects of CUR with or without SAL on colonic inflammation and pro-carcinogenic (cancer-causing) signaling proteins in azoxymethane (a colon cancer causing agent)-treated mice. This animal model represents obese humans whose colons have an increased level of inflammation, but who have not yet developed actual cancer. Mice were fed either a HFD (60% of kilocalories) or low-fat diet (LFD) (10% of kilocalories). One HFD treatment group received 0.2% CUR in the diet; one received 0.2% CUR + 0.15% SAL; and one received 0.4% CUR + 0.3% SAL. The HFD mice developed 30% greater fat mass than the LFD mice. The colonic concentrations of some key inflammation markers in the HFD mice were decreased by 50-69% by the high-dose combination regimen (0.2% CUR + 0.15% SAL). Only the combination regimens greatly suppressed activation of two important pro-carcinogenic proteins: Akt and NF-kB. In addition, the combination of CUR and SAL showed stronger suppressive effects than CUR alone, providing a scientific basis for examining whether this combination decreases the risk of CRC in obese humans.

Technical Abstract: High-fat diets (HFDs) and excess adiposity increase proinflammatory cytokines in the colon, altering gene expression in a manner that promotes the development of colorectal cancer (CRC). Thus, compounds that reduce this biochemical inflammation are potential chemopreventive agents. Curcumin (CUR), a dietary polyphenol, and salsalate (SAL), a non-steroidal anti-inflammatory drug, are both anti-inflammatories. We investigated the inhibitory effects of CUR with or without SAL on inflammatory cytokines and procarcinogenic signaling in azoxymethane (AOM)-treated A/J mice. A sub-tumorigenic AOM dose was chosen to produce a biochemical and molecular procarcinogenic colonic environment without tumors. Mice were fed either a HFD (60% of kilocalories) or low-fat diet (LFD) (10% of kilocalories). One HFD treatment group received 0.2% CUR in the diet; one received 0.2% CUR + 0.15% SAL; and one received 0.4% CUR + 0.3% SAL. The HFD mice developed 30% greater fat mass than the LFD mice (p < 0.05). The colonic concentrations of interleukin-1B (IL-1B) and interleukin-6 (IL-6) in the HFD mice were decreased by 50-69% by the high-dose combination regimen (p < 0.015). Only the combination regimens significantly suppressed phosphorylation of protein kinase B (Akt) and nuclear factor-kB (NF-kB) p65 (p < 0.044). The combination of CUR and SAL reduces the concentration of pro-inflammatory cytokines and diminishes activation of Akt and NF-kB more effectively than CUR alone, providing a scientific basis for examining whether this combination mitigates the risk of CRC in obese individuals.