Chemotherapeutic Effect of Stigmasterol in Sorafenib Treated Breast Cancer Cell Lines via Modulation of NF-κB and ERK Signaling Pathways | ||||
Egyptian Journal of Chemistry | ||||
Volume 67, Issue 3, March 2024, Page 227-234 PDF (670.78 K) | ||||
Document Type: Original Article | ||||
DOI: 10.21608/ejchem.2023.204388.7825 | ||||
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Authors | ||||
asmaa elshamy1; Gamal Omran2; Mohammad Abd-Alhaseeb3; MAHA HOUSSEN 4 | ||||
1Faculty of pharmacy damanhour university | ||||
2Biochemistry Department, Faculty of Pharmacy, Damanhour University, Egypt, postal code: 22511 | ||||
3Pharmacology and Toxicology Department, Faculty of Pharmacy, Damanhour University, Egypt, postal code: 22511 | ||||
4Biochemistry department faculty of pharmacy Damanhour University | ||||
Abstract | ||||
Abstract Breast cancer is the main predisposing factor for female tumor-related death globally, which increases the requirement to investigate the effectiveness of new drug combination strategies. Sorafenib is a multi-kinase inhibitor mainly targeting vascular endothelial growth factor receptor (VEGFR) and Ras/Raf/ Extracellular signal-regulated kinase (ERK) pathway. Stigmasterol is a phytosterol with anticancer activity targeting different oncogenic pathways. This study aimed to examine the antitumor effects of stigmasterol and sorafenib combination against MDA-MB-231 and MCF-7 breast cancer cell lines via assessing their impact on VEGF, VEGFR-2, nuclear factor kappa B (NF-κB), Ki-67, Bcl-2, ERK, and caspase-3. Cytotoxicity was investigated using the MTT assay. VEGF, VEGFR-2, ERK, NF-κB, Bcl-2, and Ki-67 levels were assessed using the ELISA technique. VEGFR-2 gene expression was assessed using the RT-PCR technique, while caspase-3 activity was investigated using the colorimetric technique. Sorafenib and stigmasterol combination reduced the levels of NF-κB, Bcl-2, Ki-67, VEGFR-2, and VEGF-A, whereas the activity of caspase-3 was increased. In addition, MCF-7 showed more favorable results than MDA-MB-231. Stigmasterol and sorafenib combination may be a promising therapeutic regimen for breast cancer treatment through modulation of NF-κB-VEGF/BCL-2 and ERK/Caspase-3 signaling axes crosstalk. | ||||
Keywords | ||||
Breast cancer; sorafenib; stigmasterol; angiogenesis; apoptosis | ||||
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