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Inhibitory effects of interferon‐β on hepatocellular carcinoma H ep G 2 via A kt/ STAT phosphorylation
Author(s) -
Ethiraj Purushoth,
Veerappan Karpagam,
Samuel Shila,
Sivapatham Sundaresan
Publication year - 2015
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12115
Subject(s) - apoptosis , interferon , cytotoxicity , phosphorylation , cancer research , signal transduction , cytotoxic t cell , chemistry , cell growth , biology , in vitro , pharmacology , microbiology and biotechnology , immunology , biochemistry
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 H ep G 2 cells. We revealed the presence of binding receptor of interferon‐β in H ep G 2 cells. The dose‐dependent inhibition on cell proliferation was observed. We demonstrated that IFN ‐β exhibited significant cytotoxicity in H ep G 2 cells mainly through phosphorylation of signal transducers and activators of transcription 2. The activation of A kt was suppressed. The stimulation of pro‐apoptotic protein expression of B ax, inhibition of anti‐apoptotic protein expression of B cl‐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‐ A kt.