# CELL GROWTH INHIBITION AND ESTROGEN ACTION

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 1990 · $149,915

## Abstract

We have discovered that p-hydroxyphenyllactic acid (HPLA) and
methyl p-hydroxyphenyllactate (MeHPLA) are endogenous ligands for
nuclear type II sites.  MeHPLA appears to be the most important of
these two compounds because it binds to type II sites with a high
affinity (Kd, nM) and will inhibit normal (rat uterus) and
malignant (MCF-7 cells) cell growth.  HPLA does not bind to type
II sites with a high binding affinity (Kd, mu M), nor does it
inhibit cell proliferation.  These results suggest MeHPLA may
regulate normal and malignant cell growth via a direct binding
interaction with nuclear type II sites, however other mechanisms
are possible.  The specific aims of this proposal are to study the
effects of MeHPLA and synthetic analogues on normal (rat uterus)
and malignant (MCF-7; T47-D; MDA-468) cell growth in vivo and in
vitro and assess these compounds as potential anti-tumor agents.
In addition, the metabolic fate of (3H)-MeHPLA will be studied in
these normal and malignant cells to determine why tumors are
deficient in this compound (1,2).  If we suspect, MeHPLA may be
"inactivated" to HPLA by esterases in malignant cells, analogues
of MeHPLA which are not inactivated in this manner may be very
effective cell growth inhibiting agents.  Since MeHPLA is the
endogenous ligand for nuclear type II sites, we will also develop
(3H)-MeHPLA exchange assays, to study this binding interaction,
and these data will be correlated with MeHPLA effects (inhibition)
on normal and malignant cell growth in vivo and in vitro.  (3H)-
MeHPLA uptake, retention, and compartmentalization (cytosol,
microsomes, mitochondria, nuclei) will also be studied in a variety
of normal and malignant tissues in vivo and in vitro.  This broad
approach will allow us to define potential sites of cell growth
regulation by MeHPLA, and intracellular mechanisms which may affect
the "availability" and activity of MeHPLA as a cell growth
regulating agent.  These baseline studies should facilitate more
definitive studies regarding the specific mechanism(s) by which
MeHPLA regulates normal and malignant cell hypertrophy and
hyperplasia.

## Key facts

- **NIH application ID:** 3173048
- **Project number:** 5R01CA035480-06
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **SAM.gov UEI:** FXKMA43NTV21
- **Principal Investigator:** BARRY Matthew MARKAVERICH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $149,915
- **Award type:** 5
- **Project period:** 1983-08-01 → 1991-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173048

## Citation

> US National Institutes of Health, RePORTER application 3173048, CELL GROWTH INHIBITION AND ESTROGEN ACTION (5R01CA035480-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173048. Licensed CC0.

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