Investigating the Promising Anticancer Activity of Cetuximab and Fenbendazole Combination as Dual CBS and VEGFR-2 Inhibitors and Endowed with Apoptotic Potential.
Norhan M EidAhmed Ali Al-KarmalawyTaha M A EldebssHeba K A ElhakimPublished in: Chemistry & biodiversity (2024)
In this work, the cytotoxicity of monoclonal antibody (Cetuximab, Ce) and Fenbendazole (Fen), as well as their combination therapy were tested with the MTT assay. On the other side, Ce, Fen, and a combination between them were subjected to a colchicine-tubulin binding test, which was conducted and compared to Colchicine as a reference standard. Besides, Ce, Fen, and the combination of them were tested against the VEGFR-2 target receptor, compared to Sorafenib as the standard medication. Moreover, the qRT-PCR technique was used to investigate the levels of apoptotic genes (p53 and Bax) and anti-apoptotic gene (Bcl-2) as well. Also, the effect of Ce, Fen, and the combination of them on the level of ROS was studied. Furthermore, the cell cycle analysis and Annexin V apoptosis assay were carried out for Ce, Fen, and a combination of them. In addition, the molecular docking studies were used to describe the molecular levels of interactions for both (Fen and colchicine) or (Fen and sorafenib) within the binding pockets of the colchicine binding site (CBS) and vascular endothelial growth factor-2 receptor (VEGFR-2), respectively.
Keyphrases
- vascular endothelial growth factor
- cell death
- cell cycle
- molecular docking
- combination therapy
- monoclonal antibody
- energy transfer
- cell proliferation
- genome wide
- healthcare
- high throughput
- oxidative stress
- squamous cell carcinoma
- dna damage
- cell cycle arrest
- signaling pathway
- molecular dynamics simulations
- binding protein
- emergency department
- metastatic colorectal cancer
- genome wide identification
- endoplasmic reticulum stress
- radiation therapy
- risk assessment
- dna binding
- single molecule