Effects of capsaicin on the initiation stage of colon cancer in rats

Author(s)

Brunno Felipe Ramos Caetano

• Document type: Master's Dissertation
• Press: Botucatu. 2017-03-20.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Medicina. Botucatu
• Defense date: 2017-02-22
• Advisor: Luis Fernando Barbisan; Maria Aparecida Marchesan Rodrigues

Abstract

Capsaicin (8-Methyl-N-vanillyl-(trans)-6-nonenamide), a lipophilic alkaloid compound, is the major pungent ingredient found in red peppers consumed worldwide. Most reports on capsaicin potential mutagenicity and genotoxicity have yielded inconsistent findings. In this study, we evaluated capsaicin putative genotoxicity and molecular mechanisms underlying anti-proliferative and pro-apoptotic effects of capsaicin on DMH-induced rat colon carcinogenesis. Male Wistar rats were randomly assigned into six experimental groups (n=16 each). During the first four weeks, corn oil was given to groups 1 and 6, while intragastric capsaicin was administered at 5mg/kg to groups 2 and 4, and at 50mg/kg to groups 3 and 5, three times/week. On weeks 3 and 4, the animals received subcutaneous injections of either DMH (groups 1-3, 40mg/kg) or EDTA (groups 4-6, vehicle), twice a week. The animals were sacrificed 24 hours (n=6) and 22 weeks (10) after DMH treatment. Capsaicin significantly decreased DMH-induced genotoxicity in peripheral blood leukocytes and fecal water genotoxicity in CaCO-2 cells, 24 hours after the last DMH administration. Capsaicin also reduced Ki-67 proliferation index and increased caspase-3 apoptosis in the colon from the DMH-treated animals. Evaluation of differential gene expression showed that capsaicin administration up-regulated genes associated with adaptive response to chemicals, apoptosis, tissue development and cell differentiation. Capsaicin reduced the number of aberrant crypt foci (ACF) and increased the number of small, well differentiated and non-invasive tumors, 22 weeks after DMH-treatment. These findings revealed that capsaicin was able to suppress cell proliferation and to induce apoptosis via NF-κB regulation and endoplasmic reticulum (ER)-stress induction, as well as to modulate genes involved in tissue development and cell differentiation, reducing the formation of ACF preneoplastic lesions and tumors. (AU)

• FAPESP's process: 14/21951-6 - Effects of capsaicin on the chemical initiation of colon carcinogenesis in rats.
• Grantee: Brunno Felipe Ramos Caetano
• Support Opportunities: Scholarships in Brazil - Master