Artículos de revistas
Anti-inflammatory Natural Product Goniothalamin Reduces Colitis-associated And Sporadic Colorectal Tumorigenesis
Registro en:
Carcinogenesis . Oxford Univ Press, v. 38, p. 51 - 63, 2017.
0143-3334
1460-2180
WOS:000397050700007
10.1093/carcin/bgw112
Autor
Vendramini-Costa
Debora Barbosa; Francescone
Ralph; Posocco
David; Hou
Vivianty; Dmitrieva
Oxana; Hensley
Harvey; de Carvalho
Joao Ernesto; Pilli
Ronaldo Aloise; Grivennikov
Sergei I.
Institución
Resumen
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 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 1 beta (IL-1 beta), 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-kappa B. 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. 38 1 51 63 National Institutes of Health National Cancer Institute P30 Cancer Center Grant [CA-006927, CA009035, NIH/NIDDK R00 DK088589] Sao Paulo Research Foundation [2014/05189-7, 2009/51602-5] Pew Scholar in Biomedical Sciences Award American Association for Cancer Research-Landon Innovator Award PA DOH CURE funds Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)