Growth inhibitory effects of interferon-alpha subtypes vary according to human liver cancer cell lines.
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.
Yano
Hirohisa
H
Department 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
Yanai
Yoshiaki
Y
Momosaki
Seiya
S
Ogasawara
Sachiko
S
Akiba
Jun
J
Kojiro
Sakiko
S
Moriya
Fukuko
F
Fukahori
Suguru
S
Kurimoto
Masashi
M
Kojiro
Masamichi
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D016898:Interferon-alpha