Dihydroartemisinin inhibits ATP6 activity, reduces energy metabolism of hepatocellular carcinoma cells, promotes apoptosis and inhibits metastasis via CANX

Dihydroartemisinin (DHA) may inhibit the migration and invasion of liver cancer cells by reducing ATP synthase production (specifically ATP1A1 and ATP5H) through the calcium/calmodulin dependent protein kinase kinase 2/solute carrier family 8 member B1 signaling pathway. However, it is unclear whether DHA regulates ATP synthase activity by modulating other calcium ion signals to inhibit the energy metabolism and the transfer of hepatocellular carcinoma (HCC) cells. Using the Gene Expression Profiling Interactive Analysis database, a search for specific expression genes in liver cancer tissues was performed. Human HCC HuH-7 and Li-7 cells were used to produce CANX overexpression and small interfering RNA cell models. The study assessed changes in cell proliferation, apoptosis, migration and invasion. Reactive oxygen species production, ATP production, mitochondrial membrane potential (JC-1), NAD