Abstract
Many studies have focused on the identification of therapeutic targets for the treatment of certain types of cancer. Wogonin is a natural flavonoid compound that exhibits a potent anti-cancer effect. The underlying mechanism of wogonin may therefore reveal an effective way to identify novel therapeutic targets. In the current study, growth curves and MTT assays were performed to determine the effects of wogonin in human gastric cancer cells (SGC-7901) and human lung adenocarcinoma cells (A549), respectively. Changes in morphology were observed using hematoxylin and eosin (H&E) staining. The activities of key enzymes in the glycolysis and tricarboxylic acid cycle were measured using spectrophotometry. Western blot analysis was performed to determine the expression levels of hypoxia inducible factor-1α (HIF-1α) and monocarboxylate transporter-4 (MCT-4). Wogonin inhibited cell proliferation in a time- and dose-dependent manner in SGC-7901 and A549 cells. H&E staining suggested that wogonin induced cell morphology changes. In SGC-7901 cells, lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) activities and adenosine triphosphate (ATP) generation were decreased significantly by wogonin treatment compared with the untreated control. In A549 cells, wogonin significantly reduced LDH activity, but exhibited no significant effects on kinase activities or ATP generation. Furthermore, wogonin significantly decreased HIF-1α and MCT-4 protein expression in SGC-7901 cells, but not in A549 cells. The results demonstrated that wogonin inhibited the energy metabolism, cell proliferation and angiogenesis in SGC-7901 and A549 cells by negatively regulating HIF-1α and MCT-4 expression. The differential regulatory roles of wogonin in metabolism-associated enzymes in human gastric cancer and lung adenocarcinoma cells indicated its various antitumor mechanisms. The different metabolic regulatory mechanisms exhibited by wogonin in different tumor tissues should therefore be considered for antitumor therapy.