Alexandra M Kane1,2,3, Cheng Liu4,5,6, Dewan T Akhter7, Diane M McKeone4, Craig A Bell7, Kristofer J Thurecht7,8, Barbara A Leggett4,5,9, Vicki L J Whitehall4,5,10. 1. QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. Alexandra.Kane@qimrberghofer.edu.au. 2. Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia. Alexandra.Kane@qimrberghofer.edu.au. 3. Conjoint Internal Medicine Laboratory, Pathology Queensland, Queensland Health, Brisbane, QLD, Australia. Alexandra.Kane@qimrberghofer.edu.au. 4. QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. 5. Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia. 6. Envoi Specialist Pathologists, Brisbane, QLD, Australia. 7. 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. 8. ARC Training Centre for Innovation in Biomedical Imaging Technology, The University of Queensland, Brisbane, QLD, Australia. 9. Department of Gastroenterology and Hepatology, The Royal Brisbane and Women's Hospital, Queensland Health, Brisbane, QLD, Australia. 10. Conjoint Internal Medicine Laboratory, Pathology Queensland, Queensland Health, Brisbane, QLD, Australia.
Abstract
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 (BrafV637E/+/Villin-CreERT2/+) 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.
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 (BrafV637E/+/Villin-CreERT2/+) 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.
Authors: Sarah Perkins; Richard D Verschoyle; Kirsti Hill; Ifat Parveen; Michael D Threadgill; Ricky A Sharma; Marion L Williams; William P Steward; Andreas J Gescher Journal: Cancer Epidemiol Biomarkers Prev Date: 2002-06 Impact factor: 4.254
Authors: Freddie Bray; Jacques Ferlay; Isabelle Soerjomataram; Rebecca L Siegel; Lindsey A Torre; Ahmedin Jemal Journal: CA Cancer J Clin Date: 2018-09-12 Impact factor: 508.702