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Published on: March 24, 2015
Growth inhibitory effects of interferon-alpha subtypes vary according to human liver cancer cell lines
Hirohisa Yano1, Yoshiaki Yanai, Seiya Momosaki
1Department of Pathology, Kurume University School of Medicine, Research Center of Innovative Cancer Therapy of the 21st Century COE Program for Medical Science, Kurume University, Kurume, Fukuoka, Japan. hiroyano@med.kurume-u.ac.jp
Background:
Interferon (IFN)-alpha preparations used in the treatment of viral and neoplastic disease consist of single or multiple IFN-alpha subtypes that may possess different biological activity, but there are no data on liver cancer cells.
Methods:
Antiproliferative effects and the mechanisms of growth inhibition of five IFN-alpha subtypes (alpha1, alpha2, alpha5, alpha8 and alpha10) were examined in vitro using 13 human liver cancer cell lines.
Results:
The antiproliferative effect of each IFN-alpha subtype was different in each cell line. The 50% growth inhibitory concentration (IC50) on an antiviral unit basis showed that alpha5 presented the most potent antiproliferative effects in 11 of the 13 cell lines, and alpha8 in two cell lines. On average, the antiproliferative effects were strong in descending order from alpha5, alpha8, alpha10, alpha2 to alpha1. On weight basis, the most potent antiproliferative effect was shown by alpha8 in nine of the 13 cell lines, alpha5 in four cell lines, and the potency of the effects on average in descending order was alpha8, alpha5, alpha10, alpha2 and alpha1. No significant difference was observed between natural and recombinant alpha2. The mechanism of growth inhibition of each subtype in HAK-1B and KMCH-1 cell lines were apoptosis and S-phase arrest, and their induction levels were related to a certain degree to the antiproliferative effects.
Conclusions:
Our findings show that the antiproliferative effect of each IFN-alpha subtype varies according to the cell line, but that the cells are relatively or absolutely responsive to alpha5 and alpha8 subtypes.
Insights
Interferon-alpha (IFN-alpha) subtypes show varying effectiveness against liver cancer cells. IFN-alpha subtypes 5 and 8 demonstrated the most potent antiproliferative effects in this study.
Area of Science:
- Hepatocellular Carcinoma Research
- Molecular Biology
- Cancer Therapeutics
Background:
- Interferon-alpha (IFN-alpha) preparations are used for viral and neoplastic diseases.
- Different IFN-alpha subtypes may have distinct biological activities.
- Limited data exists on IFN-alpha subtype efficacy in liver cancer cells.
Purpose of the Study:
- To investigate the antiproliferative effects of five IFN-alpha subtypes (alpha1, alpha2, alpha5, alpha8, alpha10) on human liver cancer cell lines.
- To elucidate the mechanisms of growth inhibition induced by these subtypes.
Main Methods:
- In vitro examination of antiproliferative effects and growth inhibition mechanisms.
- Utilized 13 distinct human liver cancer cell lines.
- Assessed five IFN-alpha subtypes: alpha1, alpha2, alpha5, alpha8, and alpha10.
Main Results:
- Significant variation in antiproliferative effects of IFN-alpha subtypes across different cell lines.
- IFN-alpha 5 was most potent in 11/13 cell lines (antiviral unit basis); IFN-alpha 8 was most potent in 9/13 cell lines (weight basis).
- Mechanisms included apoptosis and S-phase arrest, correlating with antiproliferative potency.
Conclusions:
- IFN-alpha subtype efficacy is cell-line dependent.
- Human liver cancer cells exhibit relative or absolute responsiveness to IFN-alpha 5 and IFN-alpha 8 subtypes.
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