# POLYAMINE THERAPY OF PROSTATIC CANCER

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 1993 · $186,543

## Abstract

We propose to investigate the role of polyamine toxins as potential agents
for the treatment of hormone refractory prostatic tumors.  This proposal
centers on the characterization of aziridinylputrescine which we have shown
to be cytotoxic to hormone resistant prostatic cancer cells.  We will
radiolabel the aziridinyl putrescine to determine whether we are able to
enhance its uptake to the same degree that we can enhance putrescines
uptake in vivo, i.e. from 4:1 to 100:1.  This selective enhancement
suggests that we are able to target diamines to the prostate and prostatic
tumors.  We have observed that modification of one nitrogen, but not both
nitrogens allows the amines utilization of the prostatic polyamine
transporter.  We will therefore synthesize and examine the toxicity of N-
1,N-1 dichloroethylputrescine towards prostatic tumors as well.  As these
are polyamine toxins and as intracellular modulation of polyamines is
associated with altered cell growth, we will examine how these agents
effect critical polyamine synthetic enzymes (ODC,SAMDC,SAT), their
transcription (Northern analysis of mRNA), polyamine transport activity,
polyamine modulated growth functions and cell death associated functions
such as TRPM-2.  We will evaluate means to enhance their toxic activities
in vitro and in vivo against models of rodent and human androgen dependent,
sensitive or insensitive tumor model systems.

Prostatic cancer is the leading cause of cancer in the adult male.  It is
the second leading cause of death from cancer in the adult male.  There is
no treatment available for hormone refractory prostatic cancer.  Our long
range is to develop new methods to treat hormone resistant prostatic
cancer.

## Key facts

- **NIH application ID:** 3177976
- **Project number:** 5R01CA039203-07
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **SAM.gov UEI:** KUKXRCZ6NZC2
- **Principal Investigator:** Warren D. Heston
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $186,543
- **Award type:** 5
- **Project period:** 1984-04-01 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177976

## Citation

> US National Institutes of Health, RePORTER application 3177976, POLYAMINE THERAPY OF PROSTATIC CANCER (5R01CA039203-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177976. Licensed CC0.

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