In vivo, in vitro and in silico anticancer investigation of fullerene C60 on DMBA induced breast cancer in rats.

Abstract

AIMS:

The aim of the study was to determine the protective and therapeutic effect of fullerene C60 nanoparticle on DMBA-induced breast cancer in rats.

MAIN METHODS:

In vitro cell viability was determined by the WST-1 test. In vivo analysis was performed in female Wistar Albino rats. The expression of caspase-3, Bcl-2, Nrf-2, NF-κB, TNF-α, COX-2, p53, IL-6, IL-1α ve p38α (MAPK) proteins were assessed by western blotting. Furthermore, malondialdehyde (MDA), glutathione (GSH), catalase activity (CAT), total protein levels and DNA damage were investigated. In addition, tissues were evaluated by histopathologically. In in silico analysis, the binding affinities of the fullerene C60 nanoparticle to transcription factors such as caspase-3, Bcl-2, Nrf-2, NF-κB, TNF-α, COX-2, VEGF and Akt were demonstrated by molecular docking.

KEY FINDINGS:

Treatment of MCF-7 cells at various concentrations of fullerene C60 (0.1 to 100 mg/ml) inhibited cell viability in a dose dependent manner. Fullerene C60 treated rats exhibited considerable increase in the level of caspase-3 while decrease in the level of pro-survival protein Bcl-2. Bcl-2, NF-κB, TNF-α, COX-2, IL-6, IL-1α and p38α (MAPK) protein expression levels and malondialdehyde (MDA) levels were decreased in the C60 + DMBA groups compared to the DMBA group. It was observed that caspase-3, Nrf-2 and p53 protein expression levels, glutathione (GSH) level, catalase activities (CAT) and total protein levels increased significantly which was further confirmed through the resulting DNA fragmentation.

SIGNIFICANCE:

In silico assays, fullerene C60 has been observed to have similar affinity to some crystal ligands, especially against cancer.

• Authors: Seda Beyaz, Abdullah Aslan, Ozlem Gok, Harun Uslu, Can Ali Agca, Ibrahim Hanifi Ozercan
• Journal: Life sciences (Life Sci) Vol. 291 Pg. 120281 (Feb 15 2022) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 34982963 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• Antineoplastic Agents
• Antioxidants
• Fullerenes
• NF-E2-Related Factor 2
• NF-kappa B
• Tumor Suppressor Protein p53
• Caspase 3
• Glutathione
• fullerene C60

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy, metabolism)
• Caspase 3 (metabolism)
• Cell Survival (drug effects)
• Computer Simulation
• Disease Models, Animal
• Female
• Fullerenes (chemistry, metabolism, pharmacology)
• Glutathione (metabolism)
• Humans
• MCF-7 Cells
• Molecular Docking Simulation
• NF-E2-Related Factor 2 (metabolism)
• NF-kappa B (metabolism)
• Oxidative Stress (drug effects)
• Rats
• Rats, Wistar
• Tumor Suppressor Protein p53 (metabolism)