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.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgments
The authors would like to thank the employees of the Experimental Research Unit (Unipex, Botucatu Medical School) for their support during animal experimentation.
Funding
The study was supported by the Sao Paulo Research Foundation (FAPESP) and the National Council for Scientific and Technological Development (CNPq). Brunno F.R. Caetano was the recipient of a fellowship from FAPESP (2014/21951-6). Luis F. Barbisan was the recipient of a research fellowship from CNPq (304128/2015-5). Maria A.M. Rodrigues was the recipient of a research grant from FAPESP (2014/24762-0).
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Conceptualization, MAMR and LFB; methodology, BFRC, MGI, and MBT; animal experimentation, BFRC, MBT, MGI, and LFB; writing—original draft preparation, BFRC; writing—review and editing, BFRC, NAM, GRR, LFB, and MAMR; project administration, LFB and MAMR; funding acquisition, MAMR. All authors have read and agreed to the published version of the manuscript.
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Brunno Felipe Ramos Caetano and Mariana Baptista Tablas share the first authorship.
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Caetano, B.F.R., Tablas, M.B., Ignoti, M.G. et al. Capsaicin lacks tumor-promoting effects during colon carcinogenesis in a rat model induced by 1,2-dimethylhydrazine. Environ Sci Pollut Res 28, 2457–2467 (2021). https://doi.org/10.1007/s11356-020-10683-6
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DOI: https://doi.org/10.1007/s11356-020-10683-6