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Characterization of Butyrate-Resistant Colorectal Cancer Cell Lines and the Cytotoxicity of Anticancer Drugs against These Cells

Colorectal cancer (CRC) is the third most common cancer worldwide. The gut microbiota plays a critical role in homeostasis and carcinogenesis. Butyrate, a short-chain fatty acid produced by the gut microbiota, plays a role in intestinal homeostasis and acts as an anticancer agent by inhibiting growt...

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Autores principales: Nittayaboon, Kesara, Leetanaporn, Kittinun, Sangkhathat, Surasak, Roytrakul, Sittiruk, Navakanitworakul, Raphatphorn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325644/
https://www.ncbi.nlm.nih.gov/pubmed/35909471
http://dx.doi.org/10.1155/2022/6565300
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author Nittayaboon, Kesara
Leetanaporn, Kittinun
Sangkhathat, Surasak
Roytrakul, Sittiruk
Navakanitworakul, Raphatphorn
author_facet Nittayaboon, Kesara
Leetanaporn, Kittinun
Sangkhathat, Surasak
Roytrakul, Sittiruk
Navakanitworakul, Raphatphorn
author_sort Nittayaboon, Kesara
collection PubMed
description Colorectal cancer (CRC) is the third most common cancer worldwide. The gut microbiota plays a critical role in homeostasis and carcinogenesis. Butyrate, a short-chain fatty acid produced by the gut microbiota, plays a role in intestinal homeostasis and acts as an anticancer agent by inhibiting growth and inducing apoptosis. However, microbiota studies have revealed an abnormally high abundance of butyrate-producing bacteria in patients with CRC and indicated that it leads to chemoresistance. We characterized butyrate resistance in HCT-116 and PMF-K014 CRC cells after treatment with a maximum butyrate concentration of 3.2 mM. The 50% inhibitory concentration of butyrate was increased in butyrate-resistant (BR) cells compared with that in parental (PT) cells. The mechanism of butyrate resistance was initially investigated by determining the expression of butyrate influx- and drug efflux-related genes. We found the increased expression of influx- and efflux-related genes in BR cells compared with that in PT cells. Proteomic data showed both identical and different proteins in PT and BR cells. Further analysis revealed the crossresistance of HCT-116 cells to metformin and oxaliplatin and that of PMF-K014 cells to 5-fluorouracil. Our findings suggest that the acquisition of butyrate resistance induces the development of chemoresistance in CRC cells, which may play an important role in CRC development, treatment, and metastasis.
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spelling pubmed-93256442022-07-28 Characterization of Butyrate-Resistant Colorectal Cancer Cell Lines and the Cytotoxicity of Anticancer Drugs against These Cells Nittayaboon, Kesara Leetanaporn, Kittinun Sangkhathat, Surasak Roytrakul, Sittiruk Navakanitworakul, Raphatphorn Biomed Res Int Research Article Colorectal cancer (CRC) is the third most common cancer worldwide. The gut microbiota plays a critical role in homeostasis and carcinogenesis. Butyrate, a short-chain fatty acid produced by the gut microbiota, plays a role in intestinal homeostasis and acts as an anticancer agent by inhibiting growth and inducing apoptosis. However, microbiota studies have revealed an abnormally high abundance of butyrate-producing bacteria in patients with CRC and indicated that it leads to chemoresistance. We characterized butyrate resistance in HCT-116 and PMF-K014 CRC cells after treatment with a maximum butyrate concentration of 3.2 mM. The 50% inhibitory concentration of butyrate was increased in butyrate-resistant (BR) cells compared with that in parental (PT) cells. The mechanism of butyrate resistance was initially investigated by determining the expression of butyrate influx- and drug efflux-related genes. We found the increased expression of influx- and efflux-related genes in BR cells compared with that in PT cells. Proteomic data showed both identical and different proteins in PT and BR cells. Further analysis revealed the crossresistance of HCT-116 cells to metformin and oxaliplatin and that of PMF-K014 cells to 5-fluorouracil. Our findings suggest that the acquisition of butyrate resistance induces the development of chemoresistance in CRC cells, which may play an important role in CRC development, treatment, and metastasis. Hindawi 2022-07-19 /pmc/articles/PMC9325644/ /pubmed/35909471 http://dx.doi.org/10.1155/2022/6565300 Text en Copyright © 2022 Kesara Nittayaboon et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Nittayaboon, Kesara
Leetanaporn, Kittinun
Sangkhathat, Surasak
Roytrakul, Sittiruk
Navakanitworakul, Raphatphorn
Characterization of Butyrate-Resistant Colorectal Cancer Cell Lines and the Cytotoxicity of Anticancer Drugs against These Cells
title Characterization of Butyrate-Resistant Colorectal Cancer Cell Lines and the Cytotoxicity of Anticancer Drugs against These Cells
title_full Characterization of Butyrate-Resistant Colorectal Cancer Cell Lines and the Cytotoxicity of Anticancer Drugs against These Cells
title_fullStr Characterization of Butyrate-Resistant Colorectal Cancer Cell Lines and the Cytotoxicity of Anticancer Drugs against These Cells
title_full_unstemmed Characterization of Butyrate-Resistant Colorectal Cancer Cell Lines and the Cytotoxicity of Anticancer Drugs against These Cells
title_short Characterization of Butyrate-Resistant Colorectal Cancer Cell Lines and the Cytotoxicity of Anticancer Drugs against These Cells
title_sort characterization of butyrate-resistant colorectal cancer cell lines and the cytotoxicity of anticancer drugs against these cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325644/
https://www.ncbi.nlm.nih.gov/pubmed/35909471
http://dx.doi.org/10.1155/2022/6565300
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