title: Inhibitory effects of interferon-β on hepatocellular carcinoma HepG2 via Akt/STAT phosphorylation.
abstract: Conventional chemotherapy fails to cure metastatic hepatoma mainly due to its high hepatotoxicity. Currently, doxorubicin is the most widely used drug against liver cancer either as single agent or in combination with other chemotherapeutics such as cisplatin. It is limited due to their severe toxicity on normal hepatocytes. Therefore, alternative therapeutic agents without or with low hepatotoxicity are highly desirable. Interferons are a family of cytokines that potently demonstrate antiviral, immunomodulatory, and antiproliferative activities. It also exerts direct cytotoxic effects on tumor cells. The purpose of this study was to examine the in vitro cytotoxicity of interferon-β on HepG2 cells. We revealed the presence of binding receptor of interferon-β in HepG2 cells. The dose-dependent inhibition on cell proliferation was observed. We demonstrated that IFN-β exhibited significant cytotoxicity in HepG2 cells mainly through phosphorylation of signal transducers and activators of transcription 2. The activation of Akt was suppressed. The stimulation of pro-apoptotic protein expression of Bax, inhibition of anti-apoptotic protein expression of Bcl-2, activation of cleaved caspases 9 and 3 was found at increasing concentrations. In conclusion, our results suggest that interferon-β has potential to inhibit cell proliferation dose dependently. Increased concentrations of interferon-β influenced apoptosis via mitochondrial pathway through inhibition of p-Akt.
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, Chennai, 600056, Tamilnadu, India.
authors.forename: Karpagam
authors.initials: K
authors.lastname: Veerappan
authors.affiliation: Department of Biochemistry, VRR Institute of Biomedical Science, Chennai, 600056, Tamilnadu, 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.
authors.forename: Sundaresan
authors.initials: S
authors.lastname: Sivapatham
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050795:STAT2 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D047428:Protein Kinase Inhibitors; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D016899:Interferon-beta; D051057:Proto-Oncogene Proteins c-akt
keywords: Bcl-2; HepG2; Interferon-β; bax; caspases 9 and 3; p-Akt