Synergistic anti-carcinogenic effect of interferon-β with cisplatin on human breast adenocarcinoma MDA MB231 cells
| Autor: | Karpagam Veerappan, Sundaresan Sivapatham, Balakrishnan Doraisami, Purushoth Ethiraj |
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| Rok vydání: | 2014 |
| Předmět: |
Immunology
Apoptosis Breast Neoplasms Biology Pharmacology Adenocarcinoma chemistry.chemical_compound Western blot Cell Line Tumor medicine Immunology and Allergy Cytotoxic T cell Humans Clonogenic assay Cytotoxicity Cell Proliferation bcl-2-Associated X Protein Cisplatin medicine.diagnostic_test Dose-Response Relationship Drug Caspase 3 Drug Synergism Interferon-beta Caspase 9 chemistry Proto-Oncogene Proteins c-bcl-2 Cancer cell Micronucleus test Trypan blue Drug Therapy Combination Female Immunotherapy medicine.drug |
| Zdroj: | International immunopharmacology. 23(1) |
| ISSN: | 1878-1705 |
| Popis: | Cisplatin is one of the most commonly used chemotherapeutic agents for breast cancer treatment. However, its efficacy is greatly limited by its toxic side effects. The present study investigated the synergistic effect of interferon β with cisplatin on MDA MB231 cells. The antiproliferative effect was measured by the 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The combination index (CI) was calculated using the method of Chou and Talalay. Cytotoxicity was determined by trypan blue and clonogenic assay. Genotoxic and cytostatic effects were studied using micronucleus assay and nuclear division index (NDI). Protein expression was analyzed using immunoblotting. Interferon β (100–2500 IU/mL) and Cisplatin (0.01–100 μM) had an inhibitory effect on the proliferation of cancer cells in a dose-dependent manner, with the IC50 values at 1500 IU/mL and 20 μM for interferon β and cisplatin, respectively. Western blot analysis revealed expression of interferon β binding receptor in MDA MB231 cells. More interestingly, synergistic, cytotoxic and genotoxic effects were observed after treatment with a combination of interferon β with reduced dosage of cisplatin. Decreased expression of Bcl-2 and increased expression of Bax stimulated the cytochrome c release, which triggers caspase-9 and -3 activation significantly increased in the combinational group. In conclusion the combination of interferon β with reduced dose of cisplatin results synergistically improved growth-inhibition and apoptosis-inducing effect on MDA MB231 cells. |
| Databáze: | OpenAIRE |
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