Nam Dia long, a Vietnamese folk formula, induces apoptosis in MCF-7 cells through various mechanisms of action.

BACKGROUND: The holistic approach of traditional medicine renders the identification of its mechanisms of action difficult. Microarray technology provides an efficient way to analyze the complex genome-wide gene expression of cells treated with mixtures of medicinal ingredients. We performed transcriptional profiling of MCF-7 cells treated with Nam Dia Long (NDL), a Vietnamese traditional formula, to explore the mechanism of action underlying the apoptosis inducing effect of this formula reported in a previous study. METHODS: MCF-7 cells were treated with aqueous extracts of NDL at the IC50 concentration for 24, 36 and 48 h. Total RNAs at 24 h and 48 h were subsequently extracted, reverse transcribed and submitted to microarray expression profiling using the Human HT-12 v4.0 Expression Bead Chip (Illumina). Functional analyses were performed using the Database for Annotation, Visualization and Integrated Discovery and the Ingenuity Pathways Analysis. The expression level from selected genes at the three time points were assessed by quantitative real-time RT-PCR and Western blot. RESULTS: Fifty-four and 601 genes were differentially expressed at 24 and 48 h of NDL treatment, respectively. Genes with altered expression at 24 h were mostly involved in cell responses to xenobiotic stress whereas genes differentially expressed at 48 h were related to endoplasmic reticulum stress, DNA damage and cell cycle control. Apoptosis of NDL treated MCF-7 cells resulted from a combination of different mechanisms including the intrinsic and extrinsic pathways, cell cycle arrest- and oxidative stress-related cell death. CONCLUSION: NDL elicited a two-stage response in MCF-7 treated cells with apoptosis as the ultimate result. The various mechanisms inducing apoptosis reflected the complexity of the formula composition.

Antitumor effect of the integrin α4 signaling inhibitor JK273 in non-small cell lung cancer NCI-H460 cells.

Lung cancer accounts for the highest death rate among cancers worldwide, with most patients being diagnosed with non-small cell lung cancer (NSCLC), urging more effective therapies. We report that JK273, a pyrrolo[2,3-d]pyrimidine analog, which inhibits α4 integrin signaling, showed a selective cytotoxic effect against HCI-H460 NSCLC cells, with an IC50 of 0.98 ± 0.15 µM, but showed less sensitivity to fibroblasts with a selectivity index (SI) greater than 30. This effect was attributed to cell cycle arrest at S phase by JK273 treatment, resulting in the apoptosis of NCI-H460 cells, further confirmed by exposing phosphatidylserine and morphological changes. Taken together with the previous study of JK273 inhibiting cell migration, we propose that JK273 could serve as an antitumor compound to specifically target cancer cells but not non-cancerous cells by triggering programmed cell death, in addition to anti-metastatic effects in cancer therapy.

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

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.