Growth inhibitory effects of interferon‐α subtypes vary according to human liver cancer cell lines

AbstractBackground:  Interferon (IFN)‐α preparations used in the treatment of viral and neoplastic disease consist of single or multiple IFN‐α 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‐α subtypes (α1, α2, α5, α8 and α10) were examined in vitro using 13 human liver cancer cell lines.Results:  The antiproliferative effect of each IFN‐α subtype was different in each cell line. The 50% growth inhibitory concentration (IC50) on an antiviral unit basis showed that α5 presented the most potent antiproliferative effects in 11 of the 13 cell lines, and α8 in two cell lines. On average, the antiproliferative effects were strong in descending order from α5, α8, α10, α2 to α1. On weight basis, the most potent antiproliferative effect was shown by α8 in nine of the 13 cell lines, α5 in four cell lines, and the potency of the effects on average in descending order was α8, α5, α10, α2 and α1. No significant difference was observed between natural and recombinant α2. 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‐α subtype varies according to the cell line, but that the cells are relatively or absolutely responsive to α5 and α8 subtypes.