Goniothalamin prevents the development of chemically induced and spontaneous colitis in rodents and induces apoptosis in the HT-29 human colon tumor cell line

Author(s)

Vendramini-Costa, Debora Barbosa ^{[1, 2]} ; Alcaide, Antonio ^[3] ; Pelizzaro-Rocha, Karin Juliane ^[4] ; Talero, Elena ^[3] ; Avila-Roman, Javier ^[3] ; Garcia-Maurino, Sofia ^[5] ; Pilli, Ronaldo Aloise ^[1] ; de Carvalho, Joao Ernesto ^{[6, 2]} ; Motilva, Virginia ^[3]

Affiliation

^[1] Univ Estadual Campinas, Inst Chem, Dept Organ Chem, Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Chem Biol & Agr Pluridisciplinary Res Ctr CPQBA, Campinas, SP - Brazil

^[3] Univ Seville, Fac Pharm, Dept Pharmacol, Seville - Spain

^[4] Univ Estadual Campinas, Inst Biol, Dept Biochem, Campinas, SP - Brazil

^[5] Univ Seville, Fac Biol, Dept Plant Biol & Ecol, Seville - Spain

^[6] Univ Estadual Campinas, Fac Pharmaceut Sci, Campinas, SP - Brazil

• Document type: Journal article
• Source: Toxicology and Applied Pharmacology; v. 300, p. 1-12, JUN 1 2016.
• Web of Science Citations: 5

Abstract

Colon cancer is the third most incident type of cancer worldwide. One of the most important risk factors for colon cancer development are inflammatory bowel diseases (IBD), thus therapies focusing on IBD treatment have great potential to be used in cancer prevention. Nature has been a source of new therapeutic and preventive agents and the racemic form of the styryl-lactone goniothalamin (GTN) has been shown to be a promising antiproliferative agent, with gastroprotective, antinociceptive and anti-inflammatory effects. As inflammation is a well-known tumor promoter, the major goal of this study was to evaluate the therapeutic and preventive potentials of GTN on chemically induced and spontaneous colitis, as well as the cytotoxic effects of GTN on a human colon tumor cell line (HT-29). GTN treatments inhibited TNBS-induced acute and chronic colitis development in Wistar rats, reducing myeloperoxidase levels and inflammatory cells infiltration in the mucosa. In spontaneous-colitis using IL-10 deficient mice (C57BL/6 background), GTN prevented colitis development through downregulation of TNF-alpha, upregulation of SIRT-1 and inhibition of proliferation (PCNA index), without signs of toxicity after three months of treatment. In HT-29 cells, treatment with 10 mu M of GTN induced apoptosis by increasing BAX/BCL2, p-JNK1/JNK1, p-P38/P38 ratios as well as through ROS generation. Caspase 8, 9 and 3 activation also occurred, suggesting caspase-dependent apoptotic pathway, culminating in PARP-1 cleavage. Together with previous data, these results show the importance of GTN as a pro-apoptotic, preventive and therapeutic agent for IBD and highlight its potential as a chemopreventive agent for colon cancer. (C) 2016 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 12/18281-3 - Mechanism of action of goniothalamin and derivatives: the use of fluorescent probes and folate receptors
• Grantee: Débora Barbosa Vendramini Costa
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 09/51602-5 - Chemical biology: new natural and synthetic molecular targets against cancer, structural studies, biological evaluation and mode of action
• Grantee: Ronaldo Aloise Pilli
• Support Opportunities: Research Projects - Thematic Grants