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Vendramini-Costa DB , Francescone R , Posocco D , Hou V , Dmitrieva O , Hensley H , de Carvalho JE , Pilli RA , Grivennikov SI
Anti-inflammatory natural product goniothalamin reduces colitis-associated and sporadic colorectal tumorigenesis
Carcinogenesis. 2017 Jan;38(1) :51-63
PMID: 27797827    PMCID: PMC5219049    URL: https://www.ncbi.nlm.nih.gov/pubmed/27797827
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The tumor microenvironment offers multiple targets for cancer therapy, including pro-tumorigenic inflammation. Natural compounds represent an enormous source of new anti-inflammatory and anticancer agents. We previously showed that the styryl lactone goniothalamin (GTN) has promising antiproliferative and anti-inflammatory activities. Because inflammation is a major driver of colorectal cancer (CRC), we therefore evaluated the therapeutic and preventive potentials of GTN in colitis, colitis-associated cancer (CAC) and spontaneous CRC. First, in a simplistic model of inflammation in vitro, GTN was able to inhibit cytokine production in bone marrow-derived macrophages induced by lipopolysaccharide. Next, in dextran sulfate sodium (DSS) induced-colitis model, mice treated with GTN displayed restored tissue architecture, increased cell proliferation in the colonic crypts and reduced epithelial damage. Moreover, colon tissue from GTN-treated mice had significantly less expression of the inflammatory genes interleukin 1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), S100A9, interleukin 23A (IL-23A), IL-22 and IL-17A In the azoxymethane/DSS model of CAC, GTN reduced tumor multiplicity, load and size. Additionally, GTN suppressed production of IL-6, IL-17 and TNF-alpha in tumor tissue, as well as abrogated stromal immune cell activation and nuclear translocation of NF-kappaB. Finally, in a tamoxifen inducible model of sporadic CRC, GTN-treated mice had significantly fewer tumors and decreased levels of IL-17A, IL-6, S100A9 and TNF-alpha protein within the tumors. These results suggest that GTN possesses anti-inflammatory and antitumor activities and represents a preventive and therapeutic agent modulating the inflammatory environment in the colon during colitis as well as CAC and CRC development.
Vendramini-Costa, Debora Barbosa Francescone, Ralph Posocco, David Hou, Vivianty Dmitrieva, Oxana Hensley, Harvey de Carvalho, Joao Ernesto Pilli, Ronaldo Aloise Grivennikov, Sergei I eng England 2016/11/01 06:00 Carcinogenesis. 2017 Jan;38(1):51-63. doi: 10.1093/carcin/bgw112. Epub 2016 Oct 24.