# CANCER PREVENTIVE EFFECTS OF DHEA AND ANALOGS

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 1989 · $39,043

## Abstract

Long-term oral administration of dehydroepiandrosterone (DHEA) to various
mouse strains inhibits the development of spontaneous breast cancer and
chemically induced lung and colon tumors.  Topical application of the
steroid to mouse skin inhibits DMBA-initiated and TPA-promoted tumors at
both the initiation and promotion phase and also inhibits carcinoma and
papilloma formation in the complete carcinogenesis system.  Although
long-term treatment of mice and rats with DHEA produces no apparent
side-effects, in some strains of mice and rats DHEA apparently undergoes
conversion to an estrogen and is uterotrophic.  We have prepared the novel
steroid, 3Beta-methylandrost-5-en-17-one (DE-7), which, unlike DHEA, is not
uterotrophic in the rat, and according to our early tests, is more active
than DHEA in preventing tumorigenesis, DE-7 is a clear potential cancer
chemopreventive agent.

DHEA is a potent inhibitor of mammalian glucose-6-phosphate dehydrogenase,
the first enzyme in the pentose-phosphate shunt, a major source of
extra-mitochondrial NADPH.  The anti-initiating activity of DHEA very
probably results from an inhibition of carcinogen activation, presumably by
lowering NADPH levels and reducing the activity of the mixed-function
oxidase.  DHEA treatment also inhibits O2- formation by TPA stimulated
human granulocytes.  O2- is generated by an NADPH-dependent oxidase and may
play an important role in tumor promotion.  In this proposal further
studies are planned to help elucidate the mechanism of cancer preventive
action of DHEA and DE-7 and to undertake a steroid synthetic and cancer
preventive screening program to develop additional non-estrogenic analogs
of DHEA that might have greater potency than DE-7.

## Key facts

- **NIH application ID:** 3176639
- **Project number:** 3R01CA038574-04S1
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **SAM.gov UEI:** QD4MGHFDJKU1
- **Principal Investigator:** ARTHUR G SCHWARTZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $39,043
- **Award type:** 3
- **Project period:** 1985-09-30 → 1989-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3176639

## Citation

> US National Institutes of Health, RePORTER application 3176639, CANCER PREVENTIVE EFFECTS OF DHEA AND ANALOGS (3R01CA038574-04S1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3176639. Licensed CC0.

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