Antitumor Effect of Esculetin on Sorafenib -Treated Human Hepatocellular Carcinoma Cell Lines Via Suppression of VEGF-EGFR/RAS/ERK/NF-κB Pathway and Modulation of pI3K/ P38 Axis Crosstalk
Adel, I., tantawy, M., Salahuddin, A., HOUSSEN, M. (2023). Antitumor Effect of Esculetin on Sorafenib -Treated Human Hepatocellular Carcinoma Cell Lines Via Suppression of VEGF-EGFR/RAS/ERK/NF-κB Pathway and Modulation of pI3K/ P38 Axis Crosstalk. EKB Journal Management System, 66(12), 335-346. doi: 10.21608/ejchem.2023.189470.7511
Islam Adel; mohamed A tantawy; Ahmad Salahuddin; MAHA HOUSSEN. "Antitumor Effect of Esculetin on Sorafenib -Treated Human Hepatocellular Carcinoma Cell Lines Via Suppression of VEGF-EGFR/RAS/ERK/NF-κB Pathway and Modulation of pI3K/ P38 Axis Crosstalk". EKB Journal Management System, 66, 12, 2023, 335-346. doi: 10.21608/ejchem.2023.189470.7511
Adel, I., tantawy, M., Salahuddin, A., HOUSSEN, M. (2023). 'Antitumor Effect of Esculetin on Sorafenib -Treated Human Hepatocellular Carcinoma Cell Lines Via Suppression of VEGF-EGFR/RAS/ERK/NF-κB Pathway and Modulation of pI3K/ P38 Axis Crosstalk', EKB Journal Management System, 66(12), pp. 335-346. doi: 10.21608/ejchem.2023.189470.7511
Adel, I., tantawy, M., Salahuddin, A., HOUSSEN, M. Antitumor Effect of Esculetin on Sorafenib -Treated Human Hepatocellular Carcinoma Cell Lines Via Suppression of VEGF-EGFR/RAS/ERK/NF-κB Pathway and Modulation of pI3K/ P38 Axis Crosstalk. EKB Journal Management System, 2023; 66(12): 335-346. doi: 10.21608/ejchem.2023.189470.7511

Antitumor Effect of Esculetin on Sorafenib -Treated Human Hepatocellular Carcinoma Cell Lines Via Suppression of VEGF-EGFR/RAS/ERK/NF-κB Pathway and Modulation of pI3K/ P38 Axis Crosstalk

Egyptian Journal of Chemistry
Volume 66, Issue 12, December 2023, Page 335-346  XML PDF (1006.59 K)
Document Type: Original Article
DOI: 10.21608/ejchem.2023.189470.7511
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Authors
Islam Adelorcid 1; mohamed A tantawyorcid 2; Ahmad Salahuddinorcid 3; MAHA HOUSSEN email 4
1Biochemistry Department, Faculty of Pharmacy, Damanhour University -The Egyptian Drug Authority, Cairo, Egypt
2Hormones Department, Medical Research Division, National Research Centre, Dokki, Giza, Egypt
3Biochemistry Department, Faculty of Pharmacy, Damanhour University
4Biochemistry department faculty of pharmacy Damanhour University
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Sorafenib is a multi-tyrosine kinase inhibitor used to treat HCC. However, it has many side effects and induces resistance. Esculetin is a natural compound with reported anticancer activity. This study was designedto assess the chemotherapeutic effects of the sorafenib and esculetin combination on human HCC cells.Stock solutions from sorafenib and esculetin in DMSO were prepared and then diluted by DMEM to obtain the required working concentrations. HepG2 and Huh-7 cells have been selected as in vitro model of HCC.Cytotoxicity was evaluatedusing an MTT assay. We performed flow cytometry analysis and scratch assay to assess apoptosis and migration. Finally, we quantifiedvascular endothelial growth factor (VEGF), VEGFR-2, EGFR, NF-κB, and Ki-67, PI3K, p38MAPK levels through ELISA, whileHRAS and ERK2 gene expressionwere detected through RT-PCR.The sorafenib and esculetin combination exerted a potent synergistic anti-tumor effect by modulating the EGFR and VEGF-RAS/ERK/PI3K/NF-κBaxes associated with significant upregulation of the apoptotic p38MAPK/caspase-3 axis, modulation of pI3k/p38MAPK crosstalk and inhibition of the proliferation marker Ki67.This study paves the way for using esculetin as good adjuvant to sorafenib as a promising future treatment for hepatocellular carcinoma.
Keywords
Hepatocellular carcinoma; Sorafenib; Esculetin; VEGF; NF-κB
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