Ginseng Glucosyl Oleanolate Suppresses Cervical Cancer via Simultaneous Inhibition of Glycolysis and Oxidative Phosphorylation <i>In Vivo/Vitro</i>

Ginseng, a popular functional food, owes its benefits mainly to ginsenosides with reported antitumor activity that have been widely reported for its antitumor activity. This study investigated the antitumor effect of Ginseng Glucosyl Oleanolate (GGO) on cervical cancer. GGO inhibited the activity and expression of glycolytic enzymes, hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), and lactate dehydrogenase (LDH), in HeLa cells, resulting in glycolytic inhibition. Meanwhile, GGO disturbed the TCA cycle, inhibited the expression of genes encoding respiratory Complexes II, IV, V, and reduced the mitochondrial membrane potential, which ultimately reduced the mitochondrial respiratory capacity. Furthermore, GGO inhibited the expression and nuclear interaction of β-catenin/HIF-1α, leading to energy metabolism regulation. These results of <i>in vivo</i> study were consistent with the <i>in vitro</i> study. In summary, GGO disrupted glycolysis and oxidative phosphorylation (OXPHOS), leading to an energy crisis that inhibited cell proliferation and tumor growth.