Sambucus Nigra Synergizes Cisplatin to Improve Apoptosis and Metabolic Disorders, and Reduce Drug Resistance in Two Human Breast Cancer Cell Lines

Abstract

Background: Despite modern developments in its management, still major concerns remain about drug resistance in chemotherapy. Natural adjuvants combined with chemotherapy might be the answer. We examined the anti-cancer, anti-proliferative and synergistic effects of Sambucus nigra extract with cisplatin chemotherapy (CDDP) on MCF-7 and MDA-MB-231 human cancer cell lines. Methods: MCF-7 and MDA-MB-231 cell lines were cultured in DMEM culture media, containing 10% FBS and 100 U/ml penicillin/streptomycin. The anti-proliferative activity of SNA, CDDP and their synergic doses were determined using MTT method. Next, the apoptotic, metabolic, and cellular resistance gene expressions were measured through real-time quantitative PCR technique. To show the apoptosis effects and to diagnose cellular damages, an annexin V/propidium iodide (AV/PI) kit and malondialdehyde level were performed, respectively. Results: The synergic doses of SNA and CDDP in MCF-7 were 1.25µM CDDP+1.25µM SNA and on MDA-MB-231 was 2.5µM CDDP+2.5µM SNA. The results of real-time PCR showed that SNA induced apoptosis, disrupted metabolic pathways and reduced cellular drug resistance. In addition, the combination of SNA with CDDP compared with CDDP alone was able to change the expression of these genes and increase the rate of MDA and apoptosis generation (P<0.05). Conclusion: The outcomes of this investigation indicate that SNA, as a herbal supplement, may be a candidate for increasing the effect of CDDP therapy in the treatment of breast cancers. This synergy was not estrogen-dependent in the MDA-MB-231 cells, promoted apoptosis, cell damages, disorders of metabolism, and reduced the drug resistance in the cancer cells.