Water-Soluble Pristine C₆₀ Fullerene Inhibits Liver Alterations Associated with Hepatocellular Carcinoma in Rat

Excessive production of reactive oxygen species is the main cause of hepatocellular carcinoma (HCC) initiation and progression. Water-soluble pristine C₆₀ fullerene is a powerful and non-toxic antioxidant, therefore, its effect under rat HCC model and its possible mechanisms were aimed to be discovered. Studies on HepG2 cells (human HCC) demonstrated C₆₀ fullerene ability to inhibit cell growth (IC₅₀ = 108.2 μmol), to induce apoptosis, to downregulate glucose-6-phosphate dehydrogenase, to upregulate vimentin and p53 expression and to alter HepG2 redox state. If applied to animals experienced HCC in dose of 0.25 mg/kg per day starting at liver cirrhosis stage, C₆₀ fullerene improved post-treatment survival similar to reference 5-fluorouracil (31 and 30 compared to 17 weeks) and inhibited metastasis unlike the latter. Furthermore, C₆₀ fullerene substantially attenuated liver injury and fibrosis, decreased liver enzymes, and normalized bilirubin and redox markers (elevated by 1.7-7.7 times under HCC). Thus, C₆₀ fullerene ability to inhibit HepG2 cell growth and HCC development and metastasis and to improve animal survival was concluded. C₆₀ fullerene cytostatic action might be realized through apoptosis induction and glucose-6-phosphate dehydrogenase downregulation in addition to its antioxidant activity.