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 C-60 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 C-60 fullerene ability to inhibit cell growth (IC50 = 108.2 mu mol), 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, C-60 fullerene improved post-treatment survival similar to reference 5-fluorouracil (31 and 30 compared to 17 weeks) and inhibited metastasis unlike the latter. Furthermore, C-60 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, C-60 fullerene ability to inhibit HepG2 cell growth and HCC development and metastasis and to improve animal survival was concluded. C-60 fullerene cytostatic action might be realized through apoptosis induction and glucose-6-phosphate dehydrogenase downregulation in addition to its antioxidant activity.