Ethanol extracts of Balanophora laxiflora Hemsl inhibit hepatocellular carcinoma with the involvement of HKII-mediated glycolysis

Balanophora laxiflora Hemsl has been traditionally used to treat liver cancer. Eight ingredients were identified in the ethanol extracts of Balanophora laxiflora Hemsl (BLE) by UHPLC-Q-TOF-MS/MS analysis. BLE inhibited viability and migration of HepG2 and Hepa1-6 cells, but triggered negligible apoptosis. BLE also impeded glycolysis, glucose uptake and lactate generation. Hexokinase II (HKII), a key enzyme involved in glycolysis, was significantly repressed by BLE. HKII plasmid in HepG2 enhanced cell migration, glucose uptake and cell proliferation, which were all abrogated by BLE pre-treatment. BLE incubation also down-regulated the migration and glycolysis in HKII-overexpressed Hepa1-6 cells. The anti-cancer effect of BLE in vivo was evaluated. BLE inhibited the metastasis of H22 cells in lung and alleviated orthotopic liver cancer induced by diethylnitrosamine in rats. BLE also repressed tumor growth in mice bearing HepG2 cell xenografts. Therefore, BLE can be considered as a new drug candidate for the treatment of liver cancer.