Lactobacillus plantarum-derived metabolites sensitize the tumorsuppressive effects of butyrate by regulating the functional expression of SMCT1 in 5-FU-resistant colorectal cancer cells

Hye-Ju Kim; JaeJin An; Eun-Mi Ha

doi:10.1007/s12275-022-1533-1

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Lactobacillus plantarum-derived metabolites sensitize the tumorsuppressive effects of butyrate by regulating the functional expression of SMCT1 in 5-FU-resistant colorectal cancer cells: Hye-Ju Kim ^1†, JaeJin An ^2†, Eun-Mi Ha ¹; Journal of Microbiology 2022;60(1):100-117.
DOI: https://doi.org/10.1007/s12275-022-1533-1
Published online: December 29, 2021

¹College of Pharmacy, Daegu Catholic University, Gyeongsan 38430, Republic of Korea, ²Medical Convergence Textile Center, Gyeongbuk Techno Park, Gyeongsan 38408, Republic of Korea¹College of Pharmacy, Daegu Catholic University, Gyeongsan 38430, Republic of Korea, ²Medical Convergence Textile Center, Gyeongbuk Techno Park, Gyeongsan 38408, Republic of Korea

Corresponding author: Eun-Mi Ha , Tel: +82-53-850-3612,

Received: 14 October 2021 • Revised: 12 November 2021 • Accepted: 15 November 2021

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Abstract

A critical obstacle to the successful treatment of colorectal cancer (CRC) is chemoresistance. Chemoresistant CRC cells contribute to treatment failure by providing a mechanism of drug lethargy and modifying chemoresistance-associated molecules. The gut microbiota provide prophylactic and therapeutic effects by targeting CRC through anticancer mechanisms. Among them, Lactobacillus plantarum contributes to the health of the host and is clinically effective in treating CRC. This study confirmed that 5-fluorouracil (5-FU)-resistant CRC HCT116 (HCT116/5FUR) cells acquired butyrateinsensitive properties. To date, the relationship between 5- FU-resistant CRC and butyrate resistance has not been elucidated. Here, we demonstrated that the acquisition of butyrate resistance in HCT116/5FUR cells was strongly correlated with the inhibition of the expression and function of SMCT1, a major transporter of butyrate in colonocytes. L. plantarum-cultured cell-free supernatant (LP) restored the functional expression of SMCT1 in HCT116/5FUR cells, leading to butyrate-induced antiproliferative effect and apoptosis. These results suggest that LP has a synergistic effect on the SMCT1/butyrate-mediated tumor suppressor function and is a potential chemosensitizer to overcome dual 5-FU and butyrate resistance in HCT116 cells.

Keywords: Pseudomonas aeruginosa;Staphylococcus aureus;Weigela florida;anti-inflammation

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Lactobacillus plantarum-derived metabolites sensitize the tumorsuppressive effects of butyrate by regulating the functional expression of SMCT1 in 5-FU-resistant colorectal cancer cells

J. Microbiol. 2022;60(1):100-117. Published online December 29, 2021

DOI: https://doi.org/10.1007/s12275-022-1533-1

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