Bunium persicum Seeds Extract in Combination with Vincristine Mediates Apoptosis in MCF-7 Cells through Regulation of Involved Genes and Proteins Expression

Background: Bunium persicum seeds, a member of the Apiaceae family, have historically been consumed as part of the Iranian diet. Objective: While many of this herb's biological properties have been fully investigated, there is currently no reliable information about its anticancer/cytotoxic properties. Methods: Herein, we first determined the major bioactive compounds of B. persicum seed extract (BPSE) via GC-Mass analysis. We evaluated the cytotoxicity of the extract alone as well as in combination with vincristine (VCR), a commonly used chemotherapy drug, using MTT assays on two breast cancer cell lines, MCF-7 and MDA-MB-231, as well as a normal breast cancer cell line, MCF-10A. Moreover, these compounds were evaluated in vitro for their anticancer activity using ROS assays, Real-Time PCR, Western blots, flow cytometry, and cell cycle assays. Results: As a result of our investigation, it was determined that the extract significantly reduced the viability of cancerous cells while remaining harmless to normal cells. The combination of BPSE and VCR also resulted in synergistic effects. BPSE and/or BPSE-VCR treatment increased the intracellular ROS of MCF-7 cells by over twofold. Moreover, the IC30 of BPSE (100 mu g/ml) significantly increased the BAX/BCL-2 and P53 gene expression while reducing the expression of the MYC gene. Moreover, treated cells were arrested in the G2 phase of the cell cycle. The BPSE-VCR combination synergistically reduced the NF-kappa B and increased the Caspase-7 proteins' expression. The percent of apoptosis in the cells treated with the extract, VCR, and their combination was 27, 11, and 50, respectively. Conclusions: The present study demonstrated the anticancer activity of the BPSE and its potential for application in combination therapy with VCR.