Characterization of a low-molecular-weight growth inhibitor formed by density-inhibited, tumorigenic V79 Chinese hamster cells

Abstract

A novel type of low-molecular-weight growth-inhibitory factor responsible for the density inhibition of tumorigenic V79 Chinese hamster cells has been purified, if not homogenously, by a series of reverse-phase and gel filtration high-performance liquid chromatography. The factor is an acid-stable, heat-labile substance distinct from antiproliferative nucleoside analogues or polyamines and has a molecular weight of approximately 2000. The biological activity of this inhibitor was enhanced nearly 5-fold by trypsin treatment, thereby suggesting that the inhibitor may be a precursor peptide which becomes an oligopeptide with intense biological activity by proteolysis, or that trypsin treatment allows resultant small molecules to efficiently transfer across the cytoplasmic membrane. This inhibitor reversibly inhibits the growth of a broad spectrum of cell types from neoplastic and nonneoplastic cells from various species. These data suggest that this inhibitor is primarily a growth-regulatory molecule common to mammalian cells and may play an important role in regulating growth of both normal and neoplastic cells.