Interferon-beta induces S phase accumulation selectively in human transformed cells

Interferons (IFNs) generally have been characterized as antiproliferative cytokines, The cell cycle arrest in G(1)/G(0) phase induced by type I IFNs, especially IFN-alpha, was recognized as a manifestation of their antiproliferative effects, In this article, we report that the cell cycle block in G(1)/G(0) is observed mainly in certain cell types, such as Daudi Burkitt's lymphoma cells, In a variety of human transformed cells, but not nontransformed primary cells, IFN-beta and IFN-alpha induced a significant increase in the S phase population, The increase appeared to be due to a continued S phase entry and subsequently a failure of S phase cells to transit efficiently into G(2) and M phases, The ability of tumor cells to exhibit the S phase effect correlated with proper IPN signaling and loss or inactivation of the normal G(1) checkpoint conferred by the retinoblastoma protein (pRB). Overriding the G(1) checkpoint switched human nontransformed primary cells from nonresponsive to sensitive to the IFN-induced effect. Therefore, the cell cycle regulatory machinery could function, at least in part, as a determining factor that affects the IFN-induced cell cycle effect, The IFN effect in transformed cells may suggest intriguing prospects for combinatorial therapies for cancer.