title: Interferon β improves the efficacy of low dose cisplatin by inhibiting NF-κB/p-Akt signaling on HeLa cells.
abstract: The purpose of this study was to evaluate the anticancer efficacy of interferon β in combination with low dose of cisplatin on human cervical cancer progression, as well as its principal action mechanism. The combination treatment synergistically potentiated the effect of interferon β on cell growth inhibition and DNA damage on HeLa cells by repressing NF-κB/p-Akt signaling. Synergistic targeting of these pathways has a therapeutic potential. Further, the combination treatment ameliorated the expression of pro-apoptotic Bax, and decreased the expression of anti-apoptotic protein Bcl-2. Additionally, the expression of active PARP was significantly increased and MMP-9 level was decreased in combination group as compared to the expression seen for the treatment with interferon β or cisplatin alone. Results demonstrate that the synergistic inhibitory effects of interferon β and low dose of cisplatin on human cervical cancer cells and also suggest that the inhibition of NF-κB/p-Akt signaling pathway plays a critical role in the anticancer effects of combination treatment along with the induction of PARP. Therefore, the combination of interferon β and cisplatin may be a useful treatment for human cervical cancer, with a greater effectiveness than other treatments.
authors.affiliation: Department of Medical Research, SRM Medical College Hospital and Research Centre, SRM University, Kattankulathur 603203, Tamilnadu, India.
authors.forename: Purushoth
authors.initials: P
authors.lastname: Ethiraj
authors.affiliation: Department of Biochemistry, VRR Institute of Biomedical Science (Affiliated to University of Madras), Chennai 600 056, India.
authors.forename: Karpagam
authors.initials: K
authors.lastname: Veerappan
authors.affiliation: Department of Biochemistry, VRR Institute of Biomedical Science (Affiliated to University of Madras), Chennai 600 056, India.
authors.forename: Shila
authors.initials: S
authors.lastname: Samuel
authors.affiliation: Department of Medical Research, SRM Medical College Hospital and Research Centre, SRM University, Kattankulathur 603203, Tamilnadu, India. Electronic address: prince86purush@gmail.com.
authors.forename: Sundaresan
authors.initials: S
authors.lastname: Sivapatham
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006367:HeLa Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016899:Interferon-beta / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D048631:Micronucleus, Germline / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D050795:STAT2 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D020672:I-kappa B Proteins; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D050795:STAT2 Transcription Factor; D016899:Interferon-beta; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D020780:Matrix Metalloproteinase 9; D002945:Cisplatin
keywords: Akt; Chemosensitivity; Cisplatin; Interferon β; NF-κB; PARP