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Dietary AGEs involvement in colonic inflammation and cancer: insights from an in vitro enterocyte model.

ABSTRACT: The number of colon cancer cases is increasing worldwide, and type II diabetes patients have an increased risk of developing colon cancer. Diet-borne advanced glycation end-products (AGEs) may promote neoplastic transformation; however, the mechanisms involved remain elusive. The present study helped to define the relationship between dietary AGEs and cancer progression. C2BBe1 adenocarcinoma enterocytes were exposed to 200?µg/mL glycated casein (AGEs-Csn) for up to 24?h. AGEs-Csn exposure resulted in increased cell proliferation, maladaptative changes in SOD and CAT activity and moderate levels of hydrogen peroxide (H2O2) intracellular accumulation. AGEs-Csn activated pro-survival and proliferation signalling, such as the phosphorylation of mTOR (Ser2448) and Akt (Ser473). GSK-3? phosphorylation also increased, potentially inducing extracellular matrix remodelling and thus enabling metastasis. Moreover, AGEs-Csn induced MMP-1, -3, -7, -9 and -10 expression and activated MMP-2 and MMP-9, which are regulators of the extracellular matrix and cytokine functions. AGEs-Csn induced inflammatory responses that included extracellular IL-1? at 6?h; time-dependent increases in IL-8; RAGE and NF-?B p65 upregulation; and I?B inhibition. Co-treatment with anti-RAGE or anti-TNF-? blocking antibodies and AGEs-Csn partially counteracted these changes; however, IL-8, MMP-1 and -10 expression and MMP-9 activation were difficult to prevent. AGEs-Csn perpetuated signalling that led to cell proliferation and matrix remodelling, strengthening the link between AGEs and colorectal cancer aggressiveness.

SUBMITTER: Geicu OI

PROVIDER: S-EPMC7026081 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Dietary AGEs involvement in colonic inflammation and cancer: insights from an in vitro enterocyte model.

Geicu Ovidiu I OI Stanca Loredana L Voicu Sorina N SN Dinischiotu Anca A Bilteanu Liviu L Serban Andreea I AI Calu Valentin V

Scientific reports 20200217 1

The number of colon cancer cases is increasing worldwide, and type II diabetes patients have an increased risk of developing colon cancer. Diet-borne advanced glycation end-products (AGEs) may promote neoplastic transformation; however, the mechanisms involved remain elusive. The present study helped to define the relationship between dietary AGEs and cancer progression. C2BBe1 adenocarcinoma enterocytes were exposed to 200 µg/mL glycated casein (AGEs-Csn) for up to 24 h. AGEs-Csn exposure resul ...[more]

PMID: 32066788

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Dietary AGEs involvement in colonic inflammation and cancer: insights from an in vitro enterocyte model.

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Dietary AGEs involvement in colonic inflammation and cancer: insights from an in vitro enterocyte model.

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