The anti-tumor effect of stigmasterol on sorafenib treated human breast cancer cell lines

Abstract Background: Breast cancer is the most common invasive malignancy and the leading cause of tumor-related death among women globally. Excessive angiogenesis, sustained proliferation, and evasion of apoptosis are crucial for breast cancer progression. Sorafenib is a multi-kinase receptor inhibitor with anti-angiogenic activity. Stigmasterol is a phytosterol with anticancer activity. The aim of this study was to investigate molecular mechanisms of action of sorafenib and stigmasterol in two different human breast cancer cell lines and assess their combined impact on modulation of signaling pathways that control breast cancer pathogenesis. Methods and results: MCF-7 and MDA-MB 231 cells were used as models of human breast cancer. MTT assay was used to assess cytotoxicity. Angiogenic VEGF/ VEGFR-2/ ERK/ NF-kB signaling pathway was investigated using ELISA and RT-PCR techniques. Apoptotic markers (caspase-3, Bcl2) and a proliferation marker (Ki-67) were assessed using colorimetric and ELISA techniques. Sorafenib combined with stigmasterol increased caspase-3 activity and decreased Bcl2, VEGF-A, VEGFR-2, NF-kB and Ki-67 levels. Conclusion: The combination of Sorafenib and stigmasterol may be a useful therapeutic regimen for breast cancer treatment. This combination may inhibit angiogenesis and promote apoptosis signaling.