Inhibition of Cell Proliferation by a Nuclear Type II Ligand: Methyl P-Hydroxyphenylactate

Abstract

Previous studies from our laboratory demonstrated that a variety of rat tissues contain endogenous ligands for nuclear type II sites. Since type II sites bind to [³H]estradiol with a relatively low affinity (Markaverich and Clark, 1979) and have a higher affinity for the endogenous ligands (Markaverich et al., 1983; 1984), we proposed that these compounds may regulate cell growth by their association with unclear type II binding sites. This hypothesis was supported by a number of studies which suggest that nuclear type II sites may be involved in cell growth regulation by estrogenic hormones (Markaverich et al., 1981, Clark et al., 1982). Moreover, our earlier experiments demonstrated that normal tissues contained two type II ligands (α and β) which we separated on Sephadex LH-20 (2). In contrast, malignant tissues contained only the α-peak component, suggesting that a deficinecy in the β-peak material was characteristic of tumor tissue (Markaverich et al., 1984). Our preliminary experiments also demonstrated that partially purified pareparations of the β-peak component inhibited the growth of MCF-7 human breast cancer cells in vitro, whereas this inhibition was not observed with the α-peak component.