Inhibition of mitogen stimulated growth of human colon cancer cells by interferon.
Recombinant human interferon alpha inhibits growth of a human colon cancer cell line, Colo 205. To explore the mechanisms of IFN induced growth inhibition, quiescent Colo 205 cells were stimulated to proliferate in serum-free media by defined growth factors. Addition of insulin, transferrin and selenium (ITS) stimulated DNA synthesis, as measured by 3H-thymidine incorporation, in a dose-dependent manner. IFN-alpha (at concentrations greater than 100 U ml-1) inhibited ITS stimulated DNA synthesis by 63%. Inhibition of cell cycle traverse was confirmed by flow cytometric analysis. Although IFN inhibited growth of ITS-treated cells, steady state levels of c-myc mRNA remained above levels observed in unstimulated cells. IFN inhibited DNA synthesis only when added prior to mitogen stimulation. IFN, added 6 h after exposure of quiescent cells to ITS, failed to inhibit cell growth. Addition of increasing concentrations of ITS failed to overcome the IFN-induced growth inhibition. These results suggest IFN may inhibit cell growth in part by antagonizing the action of growth factors.
Hamburger
A W
AW
University of Maryland Cancer Center, Baltimore 21201.
Condon
M E
ME
O'Donnell
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K
D002453:Cell Cycle / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006801:Humans; D007329:Insulin Antagonists / Q000494:pharmacology; D007370:Interferon Type I / Q000494:pharmacology*; D008934:Mitogens / Q000037:antagonists & inhibitors; D008938:Mitosis / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects; D012643:Selenium / Q000037:antagonists & inhibitors; D013997:Time Factors; D014168:Transferrin / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004273:DNA, Neoplasm; D007329:Insulin Antagonists; D007370:Interferon Type I; D008934:Mitogens; D012333:RNA, Messenger; D014168:Transferrin; D012643:Selenium