Related Experiment Video
Updated: Mar 20, 2026
In Vitro and In Vivo Approaches to Determine Intestinal Epithelial Cell Permeability
Published on: October 19, 2018
Effect of diclofenac on SLC16A3/MCT4 by the Caco-2 cell line
Shotaro Sasaki1, Yuya Futagi1, Masaya Ideno1
1Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan.
Abstract:
In the present study, we demonstrated that monocarboxylate transporter 4 (MCT4) is functionally expressed in Caco-2 cells. We studied the effects of 4 nonsteroidal anti-inflammatory drugs on the uptake of l-lactate as a good substrate of MCT4 by the cells. The monocarboxylate drugs inhibited the uptake of l-lactate into the cells. Diclofenac, as a member of the aryl-acetic acid group of nonsteroidal anti-inflammatory drugs, was the most potent inhibitor, with an inhibition constant of 20 μM. In the next study, we determined the type of inhibition for diclofenac. An l-lactate carrier is non-competitively inhibitable by the drug. We also demonstrated, in Xenopus oocyte expression system, potential of diclofenac for MCT4 inhibitor. The present results could provide a useful tool to discover MCT4-specific inhibitors.
Insights
Monocarboxylate transporter 4 (MCT4) is present in Caco-2 cells and its function can be inhibited by nonsteroidal anti-inflammatory drugs. Diclofenac shows potential as an MCT4 inhibitor.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Monocarboxylate transporter 4 (MCT4) plays a crucial role in cellular metabolism and lactate transport.
- Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for pain and inflammation management.
- Understanding drug interactions with transporters like MCT4 is vital for drug development and safety.
Purpose of the Study:
- To investigate the functional expression of MCT4 in Caco-2 cells.
- To evaluate the inhibitory effects of four NSAIDs on l-lactate uptake mediated by MCT4.
- To characterize the inhibitory mechanism of diclofenac on MCT4.
Main Methods:
- Utilizing Caco-2 cell models to study MCT4 expression and function.
- Assessing l-lactate uptake in the presence of various NSAIDs.
- Employing Xenopus oocyte expression systems to validate diclofenac's inhibitory potential on MCT4.
Main Results:
- Monocarboxylate transporter 4 (MCT4) was confirmed to be functionally expressed in Caco-2 cells.
- Four NSAIDs demonstrated inhibitory effects on l-lactate uptake via MCT4.
- Diclofenac exhibited the most potent inhibition, acting as a non-competitive inhibitor with an inhibition constant (Ki) of 20 μM.
- Diclofenac's potential as an MCT4 inhibitor was further supported by experiments in a Xenopus oocyte expression system.
Conclusions:
- NSAIDs, including diclofenac, can inhibit MCT4-mediated l-lactate transport.
- Diclofenac's non-competitive inhibition suggests a distinct binding interaction with MCT4.
- These findings provide a foundation for developing novel MCT4-specific inhibitors for therapeutic applications.
