Selective cytotoxicity of a Vietnamese traditional formula, Nam Dia long, against MCF-7 cells by synergistic effects

摘要

Background Nam Dia Long (NDL) is a Vietnamese traditional formula used for the treatment of some chronic diseases, including cancers, but which lacks evidence-based support. We investigated the selective cytotoxicity of NDL on some tumor cell lines and possible interactions among its ingredients leading to the overall activity. Methods Crude aqueous extracts of NDL, its ingredients including Vigna radiata (L.) Wilczek, Vigna unguiculata (L.) Walp. subsp. unguiculata, Sauropus androgynous (L.) Merr and different ingredient combinations were used for the treatment of MCF-7, Hep G2, NCI-H460 cells and normal fibroblasts. The IC₅₀ of NDL on tumor and normal cells were determined by sulforhodamine B (SRB) assay and used to calculate a selectivity index (SI). Apoptosis induction activity of NDL was determined by acridine orange - ethidium bromide (AO-EB) staining, genomic DNA and cell cycle analysis. The combination index (CI) reflecting the types of interactions among ingredients was calculated based on the median-effect principle. Real-time cell growth monitoring by the xCELLigence system was used to determine the kinetic profile of the treated MCF-7 cells. Results NDL exerted cytotoxicity on all tumor and normal cells, with the highest effect on MCF-7 cells. SI values for MCF-7, Hep G2 and NCI-H460 were 6.45, 1.61 and 1.29, respectively, indicating a high selective cytotoxicity of NDL toward MCF-7 cells. Profiles of cell death differed for MCF-7 cells and fibroblasts suggesting different mechanism of action of NDL toward these two cell types. The cytotoxicity of NDL against MCF-7 cells was due to apoptosis induction. NDL caused a cell cycle non-phase-specific effect on MCF-7 cells. CI indicated synergistic interactions among the ingredients leading to the overall activity of the complete formula. The real-time monitoring of MCF-7 cells growth after being treated with NDL and three-component combinations suggested that the presence of all ingredients was needed to reach the full cytotoxic activity. The growth kinetic profile of MCF-7 cells treated with different combinations also indicated a synergistic effect of all ingredients. Conclusion NDL exhibited selective cytotoxicity toward MCF-7 cells. This effect probably resulted from synergistic interactions among the NDL ingredients. NDL should be explored for breast cancer treatment.