Water-Soluble Pristine C<sub>60</sub> 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<sub>60</sub> fullerene is a powerful and non-toxic antioxidant, therefore, its effect under rat HCC model and its possible mechanisms w...
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| Format: | Article |
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MDPI AG
2020-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/9/794 |
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| author | Halyna Kuznietsova Natalia Dziubenko Tetiana Herheliuk Yuriy Prylutskyy Eric Tauscher Uwe Ritter Peter Scharff |
| author_facet | Halyna Kuznietsova Natalia Dziubenko Tetiana Herheliuk Yuriy Prylutskyy Eric Tauscher Uwe Ritter Peter Scharff |
| author_sort | Halyna Kuznietsova |
| collection | DOAJ |
| description | Excessive production of reactive oxygen species is the main cause of hepatocellular carcinoma (HCC) initiation and progression. Water-soluble pristine C<sub>60</sub> 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<sub>60</sub> fullerene ability to inhibit cell growth (IC<sub>50</sub> = 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, C<sub>60</sub> 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<sub>60</sub> 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<sub>60</sub> fullerene ability to inhibit HepG2 cell growth and HCC development and metastasis and to improve animal survival was concluded. C<sub>60</sub> fullerene cytostatic action might be realized through apoptosis induction and glucose-6-phosphate dehydrogenase downregulation in addition to its antioxidant activity. |
| first_indexed | 2024-03-10T17:00:06Z |
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| id | doaj.art-9587fb07a4f244fcadc549b3f9b13562 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T17:00:06Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-9587fb07a4f244fcadc549b3f9b135622023-11-20T10:59:58ZengMDPI AGPharmaceutics1999-49232020-08-0112979410.3390/pharmaceutics12090794Water-Soluble Pristine C<sub>60</sub> Fullerene Inhibits Liver Alterations Associated with Hepatocellular Carcinoma in RatHalyna Kuznietsova0Natalia Dziubenko1Tetiana Herheliuk2Yuriy Prylutskyy3Eric Tauscher4Uwe Ritter5Peter Scharff6Institute of Biology and Medicine, Taras Shevchenko National University of Kyiv, Volodymyrska str., 64, 01601 Kyiv, UkraineInstitute of Biology and Medicine, Taras Shevchenko National University of Kyiv, Volodymyrska str., 64, 01601 Kyiv, UkraineInstitute of Biology and Medicine, Taras Shevchenko National University of Kyiv, Volodymyrska str., 64, 01601 Kyiv, UkraineInstitute of Biology and Medicine, Taras Shevchenko National University of Kyiv, Volodymyrska str., 64, 01601 Kyiv, UkraineInstitute of Chemistry and Biotechnology, Technical University of Ilmenau, Weimarer str. 25, 98693 Ilmenau, GermanyInstitute of Chemistry and Biotechnology, Technical University of Ilmenau, Weimarer str. 25, 98693 Ilmenau, GermanyInstitute of Chemistry and Biotechnology, Technical University of Ilmenau, Weimarer str. 25, 98693 Ilmenau, GermanyExcessive production of reactive oxygen species is the main cause of hepatocellular carcinoma (HCC) initiation and progression. Water-soluble pristine C<sub>60</sub> 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<sub>60</sub> fullerene ability to inhibit cell growth (IC<sub>50</sub> = 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, C<sub>60</sub> 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<sub>60</sub> 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<sub>60</sub> fullerene ability to inhibit HepG2 cell growth and HCC development and metastasis and to improve animal survival was concluded. C<sub>60</sub> fullerene cytostatic action might be realized through apoptosis induction and glucose-6-phosphate dehydrogenase downregulation in addition to its antioxidant activity.https://www.mdpi.com/1999-4923/12/9/794water-soluble pristine C<sub>60</sub> fullerenehepatocellular carcinomaHepG2 cellsoxidative stress5-fluorouracilDLS measurements |
| spellingShingle | Halyna Kuznietsova Natalia Dziubenko Tetiana Herheliuk Yuriy Prylutskyy Eric Tauscher Uwe Ritter Peter Scharff Water-Soluble Pristine C<sub>60</sub> Fullerene Inhibits Liver Alterations Associated with Hepatocellular Carcinoma in Rat Pharmaceutics water-soluble pristine C<sub>60</sub> fullerene hepatocellular carcinoma HepG2 cells oxidative stress 5-fluorouracil DLS measurements |
| title | Water-Soluble Pristine C<sub>60</sub> Fullerene Inhibits Liver Alterations Associated with Hepatocellular Carcinoma in Rat |
| title_full | Water-Soluble Pristine C<sub>60</sub> Fullerene Inhibits Liver Alterations Associated with Hepatocellular Carcinoma in Rat |
| title_fullStr | Water-Soluble Pristine C<sub>60</sub> Fullerene Inhibits Liver Alterations Associated with Hepatocellular Carcinoma in Rat |
| title_full_unstemmed | Water-Soluble Pristine C<sub>60</sub> Fullerene Inhibits Liver Alterations Associated with Hepatocellular Carcinoma in Rat |
| title_short | Water-Soluble Pristine C<sub>60</sub> Fullerene Inhibits Liver Alterations Associated with Hepatocellular Carcinoma in Rat |
| title_sort | water soluble pristine c sub 60 sub fullerene inhibits liver alterations associated with hepatocellular carcinoma in rat |
| topic | water-soluble pristine C<sub>60</sub> fullerene hepatocellular carcinoma HepG2 cells oxidative stress 5-fluorouracil DLS measurements |
| url | https://www.mdpi.com/1999-4923/12/9/794 |
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