Title |
Lactobacillus plantarum-derived metabolites sensitize the tumorsuppressive effects of butyrate by regulating the functional expression of SMCT1 in 5-FU-resistant colorectal cancer cells |
Author |
Hye-Ju Kim1†, JaeJin An2†, and Eun-Mi Ha1* |
Address |
1College of Pharmacy, Daegu Catholic University, Gyeongsan 38430, Republic of Korea, 2Medical Convergence Textile Center, Gyeongbuk Techno Park, Gyeongsan 38408, Republic of Korea |
Bibliography |
Journal of Microbiology, 60(1),100-117, 2022,
|
DOI |
10.1007/s12275-022-1533-1
|
Key Words |
Lactobacillus plantarum, 5-FU resistance, butyrate
resistance, multidrug resistance, colorectal cancer cell,
SMCT1, HDAC inhibition, tumor suppression, combination
therapy |
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. |