title: Synergistic anti-carcinogenic effect of interferon-β with cisplatin on human breast adenocarcinoma MDA MB231 cells.
abstract: 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.
authors.affiliation: Department of Medical Research, SRM Medical College Hospital and Research Centre, SRM University, Kattankulathur, Tamil Nadu, India.
authors.forename: Purushoth
authors.initials: P
authors.lastname: Ethiraj
authors.affiliation: Department of Biochemistry, VRR Institute of Biomedical Science, Chennai-56, Tamil Nadu, India.
authors.forename: Karpagam
authors.initials: K
authors.lastname: Veerappan
authors.affiliation: Department of Medical Research, SRM Medical College Hospital and Research Centre, SRM University, Kattankulathur, Tamil Nadu, India.
authors.forename: Balakrishnan
authors.initials: B
authors.lastname: Doraisami
authors.affiliation: Department of Medical Research, SRM Medical College Hospital and Research Centre, SRM University, Kattankulathur, Tamil Nadu, India. Electronic address: sundarbiosrm@gmail.com.
authors.forename: Sundaresan
authors.initials: S
authors.lastname: Sivapatham
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000628:therapy*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016899:Interferon-beta / Q000008:administration & dosage*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D016899:Interferon-beta; D053148:Caspase 3; D053453:Caspase 9; D002945:Cisplatin
keywords: Bax; Bcl-2; Caspase 9; Cisplatin; Interferon-β; Synergism