Curcumin Chemoprevention Reduces the Incidence of Braf Mutant Colorectal Cancer in a Preclinical Study

被引:7
|
作者
Kane, Alexandra M. [1 ,2 ,3 ]
Liu, Cheng [1 ,2 ,4 ]
Akhter, Dewan T. [5 ]
McKeone, Diane M. [1 ]
Bell, Craig A. [5 ]
Thurecht, Kristofer J. [5 ,6 ]
Leggett, Barbara A. [1 ,2 ,7 ]
Whitehall, Vicki L. J. [1 ,2 ,3 ]
机构
[1] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia
[2] Univ Queensland, Fac Med, Brisbane, Qld, Australia
[3] Queensland Hlth, Conjoint Internal Med Lab, Pathol Queensland, Brisbane, Qld, Australia
[4] Envoi Specialist Pathologists, Brisbane, Qld, Australia
[5] Univ Queensland, Ctr Adv Imaging, Australian Inst Bioengn & Nanotechnol, ARC Ctr Excellence Bionano Sci & Technol, Brisbane, Qld, Australia
[6] Univ Queensland, ARC Training Ctr Innovat Biomed Imaging Technol, Brisbane, Qld, Australia
[7] Queensland Hlth, Royal Brisbane & Womens Hosp, Dept Gastroenterol & Hepatol, Brisbane, Qld, Australia
基金
英国医学研究理事会;
关键词
BRAF; Colorectal cancer; Curcumin; Preclinical; Chemoprevention; Sessile serrated lesion; TUMOR PROGRESSION; SERRATED PATHWAY; DNA METHYLATION; MODEL; MUTATION; SENESCENCE; EXPRESSION; LESIONS; MOUSE; CELLS;
D O I
10.1007/s10620-020-06752-y
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
引用
收藏
页码:4326 / 4332
页数:7
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