Methyl p-hydroxyphenyllactate. An inhibitor of cell growth and proliferation and an endogenous ligand for nuclear type-II binding sites.

Abstract

We previously described and partially characterized endogenous ligands for nuclear type II sites in normal and malignant tissues. Chromatography of these ligands on Sephadex LH-20 revealed that two peaks with binding activity (alpha and beta) could be resolved. The beta-peak component was present in all normal tissues that we examined, but not in malignant tissues, and it inhibited the growth of MCF-7 human breast cancer cells in vitro. Conversely, the alpha-peak component was found to be present in both normal and malignant tissues, and did not inhibit MCF-7 cell growth. The present studies describe the purification and identification of the alpha-peak and beta-peak components in bovine serum and an assessment of the effects of these compounds on normal and malignant cell growth. Gas chromatography-mass spectroscopy analysis of the purified beta-peak component demonstrated that the compound was methyl p-hydroxyphenyllactate (MeHPLA). Competition analysis revealed that MeHPLA binds to nuclear type II sites with a high binding affinity, while physiological levels of this compound blocked estradiol stimulation of uterine growth in vivo and inhibited the growth of MCF-7 human breast cancer cells in vitro. The alpha-peak component was found to be the corresponding acid, p-hydroxyphenyllactic acid (HPLA). This compound interacted with nuclear type II sites with a relatively low affinity and did not block uterotropic response to estradiol or inhibit MCF-7 cell growth. These studies demonstrate that HPLA and MeHPLA are ligands for nuclear type II sites and that MeHPLA may be a very important regulator of normal and malignant cell growth.

• Authors: B M Markaverich, R R Gregory, M A Alejandro, J H Clark, G A Johnson, B S Middleditch
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 263 Issue 15 Pg. 7203-10 (May 25 1988) ISSN: 0021-9258 [Print] United States
• PMID: 3366774 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Lactates
• Receptors, Estradiol
• Receptors, Estrogen
• methyl 4-hydroxyphenyllactate

Topics

• Animals
• Breast Neoplasms
• Cell Division (drug effects)
• Cell Line
• Cell Nucleus (metabolism)
• Chromatography, Gel
• Chromatography, High Pressure Liquid
• Female
• Humans
• Lactates (metabolism, pharmacology)
• Mass Spectrometry
• Ovariectomy
• Rats
• Rats, Inbred Strains
• Receptors, Estradiol (isolation & purification, metabolism)
• Receptors, Estrogen (metabolism)