Targeting beta-catenin signaling for prevention of colorectal cancer - Nutraceutical, drug, and dietary options.

Autor: Iloki Assanga SB; Departamento de Ciencias Químico Biológicas, Universidad de Sonora, Blvd Luis Encinas y Rosales S/N Col. Centro, Hermosillo, Sonora, C.P. 83000, Mexico. Electronic address: ilokiassanga@gmail.com., Lewis Luján LM; Technological Institute of Hermosillo (ITH), Ave. Tecnológico y Periférico Poniente S/N, Col. Sahuaro, Hermosillo, Sonora, C.P. 83170, México. Electronic address: lidianys1@yahoo.es., McCarty MF; Catalytic Longevity, San Diego, CA, 92109, USA. Electronic address: markfmccarty@gmail.com.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2023 Oct 05; Vol. 956, pp. 175898. Date of Electronic Publication: 2023 Jul 20.
DOI: 10.1016/j.ejphar.2023.175898
Abstrakt: Progressive up-regulation of β-catenin signaling is very common in the transformation of colorectal epithelium to colorectal cancer (CRC). Practical measures for opposing such signaling hence have potential for preventing or slowing such transformation. cAMP/PKA activity in colon epithelium, as stimulated by COX-2-generated prostaglandins and β2-adrenergic signaling, boosts β-catenin activity, whereas cGMP/PKG signaling has the opposite effect. Bacterial generation of short-chain fatty acids (as supported by unrefined high-carbohydrate diets, berberine, and probiotics), dietary calcium, daily aspirin, antioxidants opposing cox-2 induction, and nicotine avoidance, can suppress cAMP production in colonic epithelium, whereas cGMP can be boosted via linaclotides, PDE5 inhibitors such as sildenafil or icariin, and likely high-dose biotin. Selective activation of estrogen receptor-β by soy isoflavones, support of adequate vitamin D receptor activity with UV exposure or supplemental vitamin D, and inhibition of CK2 activity with flavanols such as quercetin, can also oppose β-catenin signaling in colorectal epithelium. Secondary bile acids, the colonic production of which can be diminished by low-fat diets and berberine, can up-regulate β-catenin activity by down-regulating farnesoid X receptor expression. Stimulation of PI3K/Akt via insulin, IGF-I, TLR4, and EGFR receptors boosts β-catenin levels via inhibition of glycogen synthase-3β; plant-based diets can down-regulate insulin and IGF-I levels, exercise training and leanness can keep insulin low, anthocyanins and their key metabolite ferulic acid have potential for opposing TLR4 signaling, and silibinin is a direct antagonist for EGFR. Partially hydrolyzed phytate can oppose growth factor-mediated down-regulation of β-catenin by inhibiting Akt activation. Multifactorial strategies for safely opposing β-catenin signaling can be complemented with measures that diminish colonic mutagenesis and DNA hypomethylation - such as avoidance of heme-rich meat and charred or processed meats, consumption of phase II-inductive foods and nutraceuticals (e.g., Crucifera), and assurance of adequate folate status.
Competing Interests: Declaration of competing interest Mark F. McCarty is co-inventor and co-owner of a US patent on nutraceutical uses of phycocyanobilin-containing oligopeptides derived from spirulina. The other authors have no conflicts of interest to declare.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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