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

• Published in: The journal of microbiology 2022, 60(1), , pp.100-117
• Main Authors: Kim, Hye-Ju, An, JaeJin, Ha, Eun-Mi
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Antineoplastic Agents - pharmacology; Apoptosis; Biomedical and Life Sciences; Butyrates - metabolism; Cancer; Cells; Chemoresistance; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - microbiology; Colorectal Neoplasms - physiopathology; Drug Resistance, Neoplasm; Fluorouracil - pharmacology; Gastrointestinal Microbiome; HCT116 Cells; Humans; Intestinal flora; Intestinal microflora; Lactobacilli; Lactobacillus plantarum; Lactobacillus plantarum - chemistry; Lactobacillus plantarum - metabolism; Lethargy; Life Sciences; Metabolites; Microbial Pathogenesis and Host-Microbe Interaction; Microbiology; Microbiota; Monocarboxylic Acid Transporters - genetics; Monocarboxylic Acid Transporters - metabolism; Neoplasms; Probiotics; Synergistic effect; Tumor suppressor genes; Tumors; 생물학
• ISSN: 1225-8873; 1976-3794
• DOI: 10.1007/s12275-022-1533-1

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 butyrate-insensitive 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.