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

Abstract Background Seeds of Bunium persicum, a member of the Apiaceae family, are traditionally consumed in the Iranian diet. Although many of its biological properties have been fully studied, no reliable information about the anticancer/cytotoxicity of this herb is available currently. Methods Herein, we first determined the major bioactive compounds of B. persicum seeds extract (BPSE) using GC-Mass analysis. Then, the cytotoxicity of the extract alone and in combination with vincristine (VCR), a common chemotherapy drug, was investigated on Breast cancer cell lines, MCF-7 and MDA-MB-231, and a normal cell line, MCF-10A, via MTT assay. Furthermore, the anticancer activity of these compounds was evaluated on MCF-7 cells through ROS assay, Real-Time PCR, Western blot, flow cytometry, and cell cycle assay. Results Our results showed that the extract considerably reduced the viability of cancerous cells while was harmless to normal ones. Besides, the combination of BPSE with VCR resulted in synergistic activity. The MCF-7 cells’ intracellular ROS increased more than 2 times after treatment with BPSE and/or BPSE-VCR. Moreover, the IC30 of BPSE (100 µg/ml) significantly increased the BAX/BCL-2 and P53 genes expression, while reducing the expression of the MYC gene. Also, the cell cycle was arrested in the G2 phase, in treated cells. The BPSE-VCR combination synergistically reduced the NF-κB and increased the Caspase-3 proteins’ expression. The percent of apoptosis in the cell treated with the extract, VCR, and their combination was 27, 11, and 50, respectively. Conclusion The present study demonstrated the anticancer activity of the BPSE and its potential for application in combination therapy with VCR.