Abstract 2799: Goniothalamin, a natural product, modulates the inflammatory microenvironment on colitis and colitis-associated cancer

Abstract

Abstract Despite anticancer drug discovery advances, the worldwide cancer incidence is remarkable. Thus, there is continuous necessity on new therapies development and tumor microenvironment offers multiple targets for cancer therapy, including inflammation. Nature has been a source of new therapeutic and preventive agents and the styryl-lactone goniothalamin (GTN) has shown to be a promising anti-proliferative and anti-inflammatory agent. In previous studies we showed that GTN has pro-apoptotic activity, gastroprotective effects and inhibits tumor development and acute inflammation in mice. Thus, the major goal of this study was to evaluate the therapeutic and preventive potentials of GTN on colitis and colitis-associate cancer (CAC) models, focusing on the elucidation of the relationship between the anti-proliferative and anti-inflammatory activities. GTN was synthesized and evaluated in vitro in LPS-stimulated RAW 264.7 murine macrophages. Cells were pre-treated with GTN (20 μM) for 3 hours and then stimulated with LPS (1 μg/mL) for 4 hours. Gene expression was analyzed by real-time PCR and cytokines production by ELISA. Experimental colitis was induced by 3.5% dextran sulfate sodium (DSS) for 7 days and animals (mice, C57-BL/6) were treated with GTN daily by oral route (30 and 100 mg/kg). CAC was induced by Azoxymethane (AOM, 10 mg/kg) followed by 3 cycles of DSS (3.0%) and treatments with GTN (30 mg/kg) were conducted by oral route, twice week. Body weight was checked every week and in the end of experiments, colon tissues were collected and processed for microscopic, biochemical and gene expression evaluations. GTN significantly reduced IL-1β, IL-6, TNF-α, IL-23, CXCL2 and iNOS expression on RAW cells, as well as levels of secreted IL-6 and TNF-α. Treatments with GTN also reduced inflammation severity on DSS-induced colitis model by reducing cytokines expression, thus suggesting a modulatory activity of the inflammatory environment. GTN treatment modulated tumor development in a mouse model of CAC. Together with previous data, these results highlight that goniothalamin can be used as a preventive and therapeutic agent to inhibit inflammation in colitis and cancer. Citation Format: Débora Barbosa Vendramini Costa, Ralph A. Francescone, Oxana Dmitrieva, Vivi Hou, David Posocco, Ronaldo A. Pilli, Sergei Grivennikov. Goniothalamin, a natural product, modulates the inflammatory microenvironment on colitis and colitis-associated cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2799. doi:10.1158/1538-7445.AM2015-2799