Luteolin induces apoptosis by impairing mitochondrial function and targeting the intrinsic apoptosis pathway in gastric cancer cells

Gastric cancer is one of the most lethal cancers worldwide. Research has focused on exploring natural medicines to improve the systematic chemotherapy for gastric cancer. Luteolin, a natural flavonoid, possesses anticancer activities. Nevertheless, the mechanism of the anticancer effects of luteolin is still not clear. The present study aimed to verify the inhibitory effect of luteolin on gastric cancer HGC-27, MFC and MKN-45 cells and to explore the underlying mechanism. A Cell Counting Kit-8 cell viability assay, flow cytometry, western blot, an ATP content assay and an enzyme activity testing assay were used. Luteolin inhibited the proliferation of gastric cancer HGC-27, MFC and MKN-45 cells. Further, it impaired mitochondrial integrity and function by destroying the mitochondrial membrane potential, downregulating the activities of mitochondrial electron transport chain complexes (mainly complexes I, III and V), and unbalancing the expression of B cell lymphoma-2 family member proteins, eventually leading to apoptosis of gastric cancer HGC-27, MFC and MKN-45 cells. The intrinsic apoptosis pathway was involved in luteolin's anti-gastric cancer effects. Furthermore, mitochondria were the main target in luteolin-induced gastric cancer apoptosis. The present study may provide a theoretical basis for the research on the effect of luteolin on the mitochondrial metabolism in cancer cells, and pave the way for its practical application in the future.