Capsaicin lacks tumor-promoting effects during colon carcinogenesis in a rat model induced by 1,2-dimethylhydrazine
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RESEARCH ARTICLE
Capsaicin lacks tumor-promoting effects during colon carcinogenesis in a rat model induced by 1,2-dimethylhydrazine Brunno Felipe Ramos Caetano 1 & Mariana Baptista Tablas 2 & Marcela Gonçalves Ignoti 2 & Nelci Antunes de Moura 2 & Guilherme Ribeiro Romualdo 2 & Luís Fernando Barbisan 2 & Maria Aparecida Marchesan Rodrigues 1 Received: 29 May 2020 / Accepted: 30 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Capsaicin (CPS, 8-methyl-N-vanillyl-trans-6-nonenamide), a pungent alkaloid from chili peppers, has contradictory effects in both experimental and human carcinogenesis. Thus, we evaluated the modifying effects of chronic CPS during the promotion and progression stages of rat colon carcinogenesis induced by 1,2-dimethylhydrazine (DMH). Male Wistar rats were given four subcutaneous injections of DMH (40 mg/body weight (b.w.)) twice a week, for 2 weeks. After DMH-induced tumor initiation, the animals were treated with CPS at 5 or 50 mg/kg b.w. by gavage for 24 weeks (three times a week). High-dose CPS reduced both cell proliferation in adjacent “normal-appearing” colonic crypts and the total number of preneoplastic aberrant crypt foci (ACF) but did not change the number of dysplastic ACF or ACF multiplicity. Although the proportion of adenomas was increased, and tubular adenocarcinomas decreased in high-dose CPS, both CPS interventions exerted no effects on total tumor incidence, volume, multiplicity, cell proliferation (Ki-67), and apoptosis (caspase-3). In accordance, high-dose CPS treatment had discrete effects on gene expression in colon tumors, as only 3/94 (3.19%) genes were significantly modified (downregulation of Cebpd and Fasl, and upregulation of Jag1). The findings of the present study show that CPS does not impact on the promotion/ progression stages of rat colon carcinogenesis. Therefore, CPS at a high-dose intervention showed to be a safe food ingredient. Keywords Capsaicin . Colon carcinogenesis . 1,2-Dimethylhydrazine . Cancer promotion and progression stages . Aberrant crypt foci and tumors
Introduction
Brunno Felipe Ramos Caetano and Mariana Baptista Tablas share the first authorship. Guilherme Ribeiro Romualdo, Luís Fernando Barbisan, and Maria Aparecida Marchesan Rodrigues share senior authorship. Responsible editor: Mohamed M. Abdel-Daim Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11356-020-10683-6) contains supplementary material, which is available to authorized users. * Luís Fernando Barbisan [email protected] 1
Department of Pathology, Medical School, São Paulo State University (UNESP), Botucatu, SP, Brazil
2
Department of Structural and Functional Biology, Biosciences Institute, São Paulo State University (UNESP), Botucatu, SP 18618-689, Brazil
Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer worldwide and a leading cause of cancer-related deaths in the USA (Bray et al. 2018; Siegel et al. 2019). According to the World Health Organization (WHO) estimates
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