Resistance to anticancer
therapeutics occurs in virtually every type of
cancer and becomes a major difficulty in
cancer treatment. Although
5-fluorouracil (
5FU) is the first-line choice of anticancer
therapy for
gastric cancer, its effectiveness is limited owing to drug resistance. Recently, altered
cancer metabolism, including the Warburg effect, a preference for glycolysis rather than oxidative phosphorylation for energy production, has been accepted as a pivotal mechanism regulating resistance to
chemotherapy. Thus, we investigated the detailed mechanism and possible usefulness of antiglycolytic agents in ameliorating
5FU resistance using established
gastric cancer cell lines, SNU620 and SNU620/
5FU. SNU620/
5FU, a
gastric cancer cell harboring resistance to
5FU, showed much higher
lactate production and expression of glycolysis-related
enzymes, such as
lactate dehydrogenase A (LDHA), than those of the parent SNU620 cells. To limit glycolysis, we examined
catechin and its derivatives, which are known anti-inflammatory and anticancer natural products because
epigallocatechin gallate has been previously reported as a suppressor of LDHA expression.
Catechin, the simplest compound among them, had the highest inhibitory effect on
lactate production and LDHA activity. In addition, the combination of
5FU and
catechin showed additional cytotoxicity and induced
reactive oxygen species (ROS)-mediated apoptosis in SNU620/
5FU cells. Thus, based on these results, we suggest
catechin as a candidate for the development of a novel adjuvant
drug that reduces chemoresistance to
5FU by restricting LDHA.