Dietary cholesterol enhances the induction and development of colonic preneoplastic lesions in C57BL/6J and BALB/cJ mice treated with azoxymethane

Rao, A.V.; Janezic, Susan A.; Friday, David; Kendall, Cyril W.C.

doi:10.1016/0304-3835(92)90268-z

Cited by 18 publications

(5 citation statements)

References 35 publications

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“…Both WT and IL‐4R α −/− mice developed ACFs after AOM treatment, which were distributed throughout the colon (Figure 1B). The number of ACFs in AOM‐treated IL‐4R α‐null mice (median 8, IQR 4–11.5; n = 9) was significantly higher than that in AOM‐treated WT mice [median 4, IQR 1–6; n = 9; p = 0.04; Mann–Whitney U ‐test) (Figure 1B)], which had a similar ACF multiplicity to previously published studies of AOM‐induced carcinogenesis in Balb/c mice 12, 14. Although IL‐4R α −/− mice demonstrated an increased number of ACFs compared with WT comparators, ACF size (based on the number of crypts per ACF) was smaller in IL‐4R α‐null mice [median 1 crypt per ACF (range 1–6) than in WT animals [median 2 crypts per ACF (range 1–16).…”

Section: Resultssupporting

confidence: 80%

“…The aberrant crypt focus (ACF) is considered to be the earliest recognizable pre‐malignant lesion during experimental colorectal carcinogenesis in rodents 10 and is increasingly recognized in humans with the advent of magnification chromo‐endoscopy 11. Colorectal ACFs develop consistently in several inbred mouse strains a few weeks after administration of the chemical carcinogen azoxymethane (AOM), several months prior to development of a smaller number of macroscopic tumours 12. However, it remains unclear whether a proportion of ACFs develop directly into advanced tumours or whether the ACF is only an indirect biomarker of tumour development.…”

Section: Introductionmentioning

confidence: 99%

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Lack of interleukin‐4 receptor α chain‐dependent signalling promotes azoxymethane‐induced colorectal aberrant crypt focus formation in Balb/c mice

Cuthbert

Orsi

et al. 2008

The Journal of Pathology

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Interleukin (IL)-4 receptor (IL-4R) alpha chain-dependent signalling by IL-4 and IL-13 promotes tumour growth and metastasis in mouse models of colorectal cancer. However, the role of IL-4R alpha-dependent signalling during the early, pre-malignant stages of colorectal carcinogenesis has not been investigated. Therefore, we investigated the effect of deletion of the IL-4R alpha gene on azoxymethane-induced colorectal aberrant crypt focus (ACF) multiplicity and size in Balb/c mice. IL-4R alpha(-/-) mice developed significantly more ACFs [median 8, inter-quartile range (IQR) 4-11.5; n = 9] than wild-type (WT) animals (median 4, IQR 1-6; n = 9; p = 0.04, Mann-Whitney U-test). There were significantly higher levels of IL-4 in serum from azoxymethane- and sham-treated IL-4R alpha(-/-) mice than WT animals, but no difference in serum IL-13 levels. In the absence of functional IL-4Rs, IL-13 can also signal via the IL-13R alpha2 receptor, leading to induction of transforming growth factor (TGF) beta, which has pro-tumourigenic activity at early stages of intestinal tumourigenesis. We found that mucosal TGFbeta mRNA levels and intestinal epithelial cell TGFbeta immunoreactivity were significantly higher in IL-4R alpha(-/-) mice than in WT animals. In summary, IL-4R alpha-dependent signalling has a protective, anti-neoplastic role during the post-initiation phase of azoxymethane-induced colorectal carcinogenesis in Balb/c mice. Our data should prompt thorough investigation of the role of IL-4R alpha-dependent signalling during human colorectal carcinogenesis, particularly as antagonism of IL-4R signalling represents a therapeutic strategy for asthma and other allergic diseases.

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Section: Resultssupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Lack of interleukin‐4 receptor α chain‐dependent signalling promotes azoxymethane‐induced colorectal aberrant crypt focus formation in Balb/c mice

Cuthbert

Orsi

et al. 2008

The Journal of Pathology

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“…Azoxymethane-induced colorectal cancer is a well-known pre-clinical model for cancer chemopreventive studies 20 , 21 . We adopted this model to test the efficacy of cardamonin (Fig.…”

Section: Resultsmentioning

confidence: 99%

Cardamonin inhibits colonic neoplasia through modulation of MicroRNA expression

James

Aparna

Paul

et al. 2017

Sci Rep

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Colorectal cancer is currently the third leading cause of cancer related deaths. There is considerable interest in using dietary intervention strategies to prevent chronic diseases including cancer. Cardamonin is a spice derived nutraceutical and herein, for the first time we evaluated the therapeutic benefits of cardamonin in Azoxymethane (AOM) induced mouse model of colorectal cancer. Mice were divided into 4 groups of which three groups were given six weekly injections of AOM. One group served as untreated control and remaining groups were treated with either vehicle or Cardamonin starting from the same day or 16 weeks after the first AOM injection. Cardamonin treatment inhibited the tumor incidence, tumor multiplicity, Ki-67 and β-catenin positive cells. The activation of NF-kB signaling was also abrogated after cardamonin treatment. To elucidate the mechanism of action a global microRNA profiling of colon samples was performed. Computational analysis revealed that there is a differential expression of miRNAs between these groups. Subsequently, we extend our findings to human colorectal cancer and found that cardamonin inhibited the growth, induces cell cycle arrest and apoptosis in human colorectal cancer cell lines. Taken together, our study provides a better understanding of chemopreventive potential of cardamonin in colorectal cancer.

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“…Highlighting the contribution of dietary cholesterol to CRC and underscoring the role of dietary-free cholesterol in its pathophysiology is crucial for a comprehensive understanding of the subject. Numerous studies have demonstrated the potential link between dietary cholesterol and CRC (63). A diet high in cholesterol has been associated with an increased risk of CRC development, with cholesterol-rich foods, such as red meat and high-fat dairy products, particularly implicated (64).…”

Section: Diets and Risk Of Colorectal Cancermentioning

confidence: 99%

Cholesterol in colorectal cancer: an essential but tumorigenic precursor?

He,

Lan,

Jin

et al. 2023

Front. Oncol.

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Colorectal cancer (CRC) is one of the most lethal human malignancies, and with the growth of societies and lifestyle changes, the rate of people suffering from it increases yearly. Important factors such as genetics, family history, nutrition, lifestyle, smoking, and alcohol can play a significant role in increasing susceptibility to this cancer. On the other hand, the metabolism of several macromolecules is also involved in the fate of tumors and immune cells. The evidence discloses that cholesterol and its metabolism can play a role in the pathogenesis of several cancers because there appears to be an association between cholesterol levels and CRC, and cholesterol-lowering drugs may reduce the risk. Furthermore, changes or mutations of some involved genes in cholesterol metabolism, such as CYP7A1 as well as signaling pathways, such as mitogen-activated protein kinase (MAPK), can play a role in CRC pathogenesis. This review summarized and discussed the role of cholesterol in the pathogenesis of CRC as well as available cholesterol-related therapeutic approaches in CRC.

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Dietary cholesterol enhances the induction and development of colonic preneoplastic lesions in C57BL/6J and BALB/cJ mice treated with azoxymethane

Cited by 18 publications

References 35 publications

Lack of interleukin‐4 receptor α chain‐dependent signalling promotes azoxymethane‐induced colorectal aberrant crypt focus formation in Balb/c mice

Lack of interleukin‐4 receptor α chain‐dependent signalling promotes azoxymethane‐induced colorectal aberrant crypt focus formation in Balb/c mice

Cardamonin inhibits colonic neoplasia through modulation of MicroRNA expression

Cholesterol in colorectal cancer: an essential but tumorigenic precursor?

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