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Antrodia Camphorata Supplement in the Early Life Inhibits Intestinal Tumorigenesis Later in Young Adult APC1638N Mice

OBJECTIVES: Colorectal cancer (CRC) is a critical burden in the U.S. with a temporal increase in incidence in young adults. Evidence shows that early-life events greatly contribute to the development of CRC, particularly early-life nutrition. Recently, a limited number of studies showed that mushroo...

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Autores principales: Lin, Ting-Chun, Tang, Ying, Chung, Soonkyu, Liu, Zhenhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9193504/
http://dx.doi.org/10.1093/cdn/nzac052.015
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author Lin, Ting-Chun
Tang, Ying
Chung, Soonkyu
Liu, Zhenhua
author_facet Lin, Ting-Chun
Tang, Ying
Chung, Soonkyu
Liu, Zhenhua
author_sort Lin, Ting-Chun
collection PubMed
description OBJECTIVES: Colorectal cancer (CRC) is a critical burden in the U.S. with a temporal increase in incidence in young adults. Evidence shows that early-life events greatly contribute to the development of CRC, particularly early-life nutrition. Recently, a limited number of studies showed that mushroom Antrodia camphorate (AC) possesses promising health-promoting effects such as anti-inflammation and anti-tumorigenesis. The present study aims to investigate the effects of the addition of AC into a high-fat diet during early life on the development of intestinal tumorigenesis in young adult APC(1638N) mice. METHODS: Mice (4 weeks of age) were fed a low-fat diet (N = 10; LFD: 10% kcal from fat) or a high-fat diet (N = 11; HFD: 60% kcal from fat) or their combinations with AC (N = 12 for each; AC: 90 mg/kg) from 4 to 12 weeks of age equivalent to childhood and adolescence in humans. After that, all groups were switched to standard chow diet (LabDiet 5P76) and fed for additional 12 weeks before sacrifice at 24 weeks of age equivalent to young adult in humans. Tumor incidences and sizes were recorded during the dissection after sacrifice. The expressions of a panel of inflammatory mediators, insulin-like growth factor-1 (IGF-1) signaling, as well as tumorigenic Wnt-signaling in the intestine were assessed. RESULTS: Body weight in HFD groups significantly increased after 8 weeks feeding than in LFD groups (p < 0.05), but AC supplement did not result in significant body weight change. After switching to chow diet for additional 12 weeks, the body weight remained higher but with a reduced degree of magnitude. Regardless LF or HF, AC supplement suppressed tumor incidence and multiplicity with a significance shown for female mice (p < 0.05). The addition of AC decreased gene expressions of inflammatory mediators (Tnf-α, IL-6, IL-10, Cox-2, and CCL2), IGF1, IGF1 receptor and cMyc in the intestine (p < 0.05). At protein level, AC supplement significantly attenuated the expression of phospho-MEK and phospho-ERK1/2 in the IGF-1 signaling and phosph-GSK-3β and β-catenin in the Wnt-signaling in the intestine of mice fed with HFD (p < 0.05). CONCLUSIONS: AC supplement during the early life exhibits potential capabilities to inhibit intestinal tumorigenesis at the young adult in mice, and the effects are particularly evident for mice fed a HFD in early life. FUNDING SOURCES: US Department of Agriculture Hatch funding.
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spelling pubmed-91935042022-06-14 Antrodia Camphorata Supplement in the Early Life Inhibits Intestinal Tumorigenesis Later in Young Adult APC1638N Mice Lin, Ting-Chun Tang, Ying Chung, Soonkyu Liu, Zhenhua Curr Dev Nutr Diet and Cancer OBJECTIVES: Colorectal cancer (CRC) is a critical burden in the U.S. with a temporal increase in incidence in young adults. Evidence shows that early-life events greatly contribute to the development of CRC, particularly early-life nutrition. Recently, a limited number of studies showed that mushroom Antrodia camphorate (AC) possesses promising health-promoting effects such as anti-inflammation and anti-tumorigenesis. The present study aims to investigate the effects of the addition of AC into a high-fat diet during early life on the development of intestinal tumorigenesis in young adult APC(1638N) mice. METHODS: Mice (4 weeks of age) were fed a low-fat diet (N = 10; LFD: 10% kcal from fat) or a high-fat diet (N = 11; HFD: 60% kcal from fat) or their combinations with AC (N = 12 for each; AC: 90 mg/kg) from 4 to 12 weeks of age equivalent to childhood and adolescence in humans. After that, all groups were switched to standard chow diet (LabDiet 5P76) and fed for additional 12 weeks before sacrifice at 24 weeks of age equivalent to young adult in humans. Tumor incidences and sizes were recorded during the dissection after sacrifice. The expressions of a panel of inflammatory mediators, insulin-like growth factor-1 (IGF-1) signaling, as well as tumorigenic Wnt-signaling in the intestine were assessed. RESULTS: Body weight in HFD groups significantly increased after 8 weeks feeding than in LFD groups (p < 0.05), but AC supplement did not result in significant body weight change. After switching to chow diet for additional 12 weeks, the body weight remained higher but with a reduced degree of magnitude. Regardless LF or HF, AC supplement suppressed tumor incidence and multiplicity with a significance shown for female mice (p < 0.05). The addition of AC decreased gene expressions of inflammatory mediators (Tnf-α, IL-6, IL-10, Cox-2, and CCL2), IGF1, IGF1 receptor and cMyc in the intestine (p < 0.05). At protein level, AC supplement significantly attenuated the expression of phospho-MEK and phospho-ERK1/2 in the IGF-1 signaling and phosph-GSK-3β and β-catenin in the Wnt-signaling in the intestine of mice fed with HFD (p < 0.05). CONCLUSIONS: AC supplement during the early life exhibits potential capabilities to inhibit intestinal tumorigenesis at the young adult in mice, and the effects are particularly evident for mice fed a HFD in early life. FUNDING SOURCES: US Department of Agriculture Hatch funding. Oxford University Press 2022-06-14 /pmc/articles/PMC9193504/ http://dx.doi.org/10.1093/cdn/nzac052.015 Text en © The Author 2022. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Diet and Cancer
Lin, Ting-Chun
Tang, Ying
Chung, Soonkyu
Liu, Zhenhua
Antrodia Camphorata Supplement in the Early Life Inhibits Intestinal Tumorigenesis Later in Young Adult APC1638N Mice
title Antrodia Camphorata Supplement in the Early Life Inhibits Intestinal Tumorigenesis Later in Young Adult APC1638N Mice
title_full Antrodia Camphorata Supplement in the Early Life Inhibits Intestinal Tumorigenesis Later in Young Adult APC1638N Mice
title_fullStr Antrodia Camphorata Supplement in the Early Life Inhibits Intestinal Tumorigenesis Later in Young Adult APC1638N Mice
title_full_unstemmed Antrodia Camphorata Supplement in the Early Life Inhibits Intestinal Tumorigenesis Later in Young Adult APC1638N Mice
title_short Antrodia Camphorata Supplement in the Early Life Inhibits Intestinal Tumorigenesis Later in Young Adult APC1638N Mice
title_sort antrodia camphorata supplement in the early life inhibits intestinal tumorigenesis later in young adult apc1638n mice
topic Diet and Cancer
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9193504/
http://dx.doi.org/10.1093/cdn/nzac052.015
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