# POLYAMINE THERAPY OF PROSTATIC CANCER

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 1989 · $137,434

## Abstract

Our long-range goal is to develop effective therapies for prostatic
cancer.  We have shown that aziridinyl putrescine (AZP) is toxic
to prostatic cells.  We propose to synthesize 3H-aziridinyl
putrescine in order to determine its uptake, metabolism, and
covalent binding to DNA, RNA and protein.

We have shown that polyamine depletion by inhibitors of
polyamine synthesis such as alpha-difluoromethylornithine reduces
intracellular content of polyamines in the prostate and prostatic
cell lines in vivo and in vitro.  This is accompanied by an enhanced
uptake of extracellular amines such as putrescine and AZP.  The
resultant increased uptake of AZP into the polyamine-depleted
cell increases AZP's cytotoxic activity.  Other manipulations have
been shown to increase or decrease cellular uptake of polyamines
and putrescine.  Using cell growth assays, we will similarly
determine whether these manipulations will increase or decrease
the toxicity of AZP.

AZP is an aziridine and potential alkylating agent.  We will also
examine the activity of biochemical response modifiers and other
cytotoxic agents for their ability to enhance the toxicity of AZP.

We will determine the uptake of AZP into R3327 slow-growing,
well-differentiated Copenhagen rat prostatic tumor variants and
human tumor xenographs in vitro.  We will investigate those
tumors with high AZP uptake to determine whether they will
demonstrate a cytotoxic response to AZP in vivo.  We will
synthesize new cytotoxic derivatives of putrescine and determine
whether these agents are similarly toxic to prostate cells.

Prostatic cancer is the second major cause of cancer deaths in
adult males in the United States.  No effective forms of
chemotherapy are available to treat this disease.  Because of the
high uptake of putrescine into prostatic tissue, it may be that
cytotoxic putrescine derivatives offer a new avenue to approach
the treatment of this disease.

## Key facts

- **NIH application ID:** 3177975
- **Project number:** 5R01CA039203-05
- **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:** 1989
- **Award amount:** $137,434
- **Award type:** 5
- **Project period:** 1984-04-01 → 1991-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177975

## Citation

> US National Institutes of Health, RePORTER application 3177975, POLYAMINE THERAPY OF PROSTATIC CANCER (5R01CA039203-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177975. Licensed CC0.

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