Evaluation of the preventive and therapeutic potential of goniothalamin in colitis associated colon cancer and in sporadic colon cancer models

• Grant number: 14/05189-7
• Support type: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): July 01, 2014
• Effective date (End): June 30, 2015
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal researcher: Ronaldo Aloise Pilli
• Grantee: Débora Barbosa Vendramini Costa
• Supervisor abroad: Sergei I. Grivennikov
• Home Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Research place: Fox Chase Cancer Center (FCCC), United States
• Associated to the scholarship: 12/18281-3 - Mechanism of action of goniothalamin and derivatives: the use of fluorescent probes and folate receptors, BP.PD

Abstract

There is well-documented connection between inflammation and cancer, with chronic inflammation preceding the development of approximately 15-20% of all cancers. However, actually the majority of all solid tumors demonstrate a paradoxical ability to recruit inflammatory cells and to upregulate inflammatory mediators, such as cytokines, to aid tumor progression. We defined this process as 'Tumor elicited inflammation' (TEI) and suggested that in colorectal cancer (CRC), TEI is induced early during the process of tumorigenesis, particularly because of the oncogene-induced, tumor site-specific deterioration of epithelial barrier and translocation of microbial products into the tumor. Colorectal cancer (CRC) is the second cause of death among all cancers in the US, despite important advances in detection, surgery and chemotherapy. Anti-inflammatory drugs improve survival in colorectal cancer (CRC), demonstrating the importance of inflammation in tumor progression. Apart from aspirin, none of anti-inflammatory drug have made it to clinics yet, either for cancer prevention, treatment or both. In this sense, this proposal, which is part of the post-doctoral project "Mechanism of action of Goniothalamin and derivatives. The use of fluorescent probes and folate receptors", aims at studying goniothalamin (GTN), a styrylactone with anti-inflammatory and anti-cancer activities in a mouse model of colitis-associated and spontaneous colon cancers. Previous studies carried by the proponent during her PhD's and regular post-doctoral project show that GTN has antiproliferative activity against human tumor cell lines, presenting also in vivo antitumor and anti-inflammatory activities, with no signs of toxicity. Thus, the extensive preliminary data obtained so far warrant further investigation of the GTN effects and molecular mechanisms of action towards inflammation - induced cancers and tumor elicited inflammation in spontaneous cancers. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VENDRAMINI-COSTA, DEBORA BARBOSA; FRANCESCONE, RALPH; POSOCCO, DAVID; HOU, VIVIANTY; DMITRIEVA, OXANA; HENSLEY, HARVEY; DE CARVALHO, JOAO ERNESTO; PILLI, RONALDO ALOISE; GRIVENNIKOV, SERGEI I.. Anti-inflammatory natural product goniothalamin reduces colitis-associated and sporadic colorectal tumorigenesis. Carcinogenesis, v. 38, n. 1, p. 51-63, JAN 2017. (09/51602-5, 14/05189-7)