| First Author | Vendramini-Costa DB | Year | 2017 |
| Journal | Carcinogenesis | Volume | 38 |
| Issue | 1 | Pages | 51-63 |
| PubMed ID | 27797827 | Mgi Jnum | J:237993 |
| Mgi Id | MGI:5817835 | Doi | 10.1093/carcin/bgw112 |
| Citation | Vendramini-Costa DB, et al. (2017) Anti-inflammatory natural product goniothalamin reduces colitis-associated and sporadic colorectal tumorigenesis. Carcinogenesis 38(1):51-63 |
| abstractText | 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. |
