Krebswissenschaft und -therapie

Exposure to Interferon γ Decreases Levels and Activity of Key Cell Cycle Proteins Resulting in Severe Growth Arrest of the Human Non-Transformed Cell Line, WISH

Abstract

Surabhi Vashistha and Parthasarathi Ajitkumar

Interferon ? (IFN?), a potent inhibitor of proliferation,inducer of apoptosis and an immune modulator of mammalian cells, has been used as an anticancer agent in cancer therapy. Several molecular mechanisms, depending upon the differences in the lineage of transformed cell targets, have been elucidated for the growth inhibition or apoptosis of target cancer cells by IFN?. However, its mechanism of action on normal cells needs to be understood from the point of view of: (i) The effect of IFN? on non-transformed cell line and (ii) The side effect of interferon therapy on normal cells in cancer patients. Using the non-transformed cell line, human foetal epithelial cell line (WISH), our earlier studies had shown that IFN? detains cells at a point prior to the activation step of cyclin dependent kinase 2 (CDK2) in the G1 phase of cell cycle. In the present study, we identifi ed significant reduction in the levels and/or activity of cyclin E-CDK2, CDC25A phosphatase, cyclin H, cyclin E, cyclin D, p21 and p27. The drastic decrease in the levels and/or activity of cyclin E and/or of cyclin E-CDK2 complex might have caused growth arrest of WISH cells by IFN?.