Curcumin Chemoprevention Reduces the Incidence of Braf Mutant Colorectal Cancer in a Preclinical Study.
Autor: | Kane AM; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. Alexandra.Kane@qimrberghofer.edu.au.; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia. Alexandra.Kane@qimrberghofer.edu.au.; Conjoint Internal Medicine Laboratory, Pathology Queensland, Queensland Health, Brisbane, QLD, Australia. Alexandra.Kane@qimrberghofer.edu.au., Liu C; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; Envoi Specialist Pathologists, Brisbane, QLD, Australia., Akhter DT; Centre for Advanced Imaging, Australian Institute for Bioengineering and Nanotechnology, ARC Centre of Excellence in Bio-Nano Science and Technology, The University of Queensland, Brisbane, QLD, Australia., McKeone DM; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., Bell CA; Centre for Advanced Imaging, Australian Institute for Bioengineering and Nanotechnology, ARC Centre of Excellence in Bio-Nano Science and Technology, The University of Queensland, Brisbane, QLD, Australia., Thurecht KJ; Centre for Advanced Imaging, Australian Institute for Bioengineering and Nanotechnology, ARC Centre of Excellence in Bio-Nano Science and Technology, The University of Queensland, Brisbane, QLD, Australia.; ARC Training Centre for Innovation in Biomedical Imaging Technology, The University of Queensland, Brisbane, QLD, Australia., Leggett BA; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; Department of Gastroenterology and Hepatology, The Royal Brisbane and Women's Hospital, Queensland Health, Brisbane, QLD, Australia., Whitehall VLJ; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; Conjoint Internal Medicine Laboratory, Pathology Queensland, Queensland Health, Brisbane, QLD, Australia. |
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Jazyk: | angličtina |
Zdroj: | Digestive diseases and sciences [Dig Dis Sci] 2021 Dec; Vol. 66 (12), pp. 4326-4332. Date of Electronic Publication: 2021 Jan 02. |
DOI: | 10.1007/s10620-020-06752-y |
Abstrakt: | Background: Colorectal cancer is a leading cause of cancer-related death worldwide and approximately 20% of cases can be attributed to a mutation in the BRAF oncogene. Curcumin is a promising chemopreventive agent with various anti-cancer benefits. Although curcumin has been reported to have poor bioavailability, this limitation has been overcome by the formulation of nano-carriers. In this preclinical study, we investigated the ability of an improved formulation of curcumin to reduce the incidence of Braf mutant carcinoma. Aim: To investigate curcumin as a chemopreventive for Braf mutant colorectal cancer in a preclinical study utilizing a murine model of serrated neoplasia. Methods: An intestine-specific Braf mutant murine model (Braf V637E/+ /Villin-Cre ERT2/+ ) was administered curcumin micelles (240 mg/kg, n = 69) in normal drinking water. Mice in the control group consumed normal drinking water (n = 83). Mice were euthanized at 14 months and the incidence of murine serrated lesions and carcinoma in each cohort were determined by histologic examination. Results: At completion of the study (14 months), it was found that curcumin did not reduce the incidence or multiplicity of murine serrated lesions but did significantly reduce the number of invasive carcinomas (RR 0.83, 95% CI 0.69-0.9985, P = 0.0360) compared to control. Conclusions: We have performed the first long-term study assessing curcumin's effect on the development of serrated neoplasia. We found that curcumin significantly reduces the risk of developing Braf mutant colorectal cancer. Our data supports further investigation of curcumin as a chemopreventive to reduce the risk of colorectal cancer arising via the serrated pathway. (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.) |
Databáze: | MEDLINE |
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