Inhibition of tumor development by dehydroepiandrosterone and related steroids.

Schwartz, Arthur G.; Pashko, Laura; Whitcomb, Jeannette M.

doi:10.1177/019262338601400312

Cited by 101Bioactive Compounds and Antitumor AgentsCancer and biochemical researchCarcinogens and Genotoxicity Assessment

Inhibition of tumor development by dehydroepiandrosterone and related steroids.

Schwartz, Arthur G., Pashko, Laura, Whitcomb, Jeannette M.·1986·Toxicologic Pathology

DOI 10.1177/019262338601400312

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Abstract

The naturally occurring adrenal steroid, dehydroepiandrosterone (DHEA), is a potent non-competitive inhibitor of mammalian glucose-6-phosphate dehydrogenase (G6PDH). Oral administration of DHEA to mice inhibits spontaneous breast cancer and chemically induced tumors of the lung and colon. Topical application of DHEA to mouse skin inhibits 7,12-dimethylbenz(a)anthracene (DMBA)-initiated and tetradecanoylphorbol-13-acetate (TPA)-promoted papillomas and DMBA-induced carcinomas at both the initiation and promotion phase. Evidence is presented that critical steps in the initiation process (mixed-function oxidase activation of a carcinogen) and promotion process (enhanced rates of cell proliferation and superoxide formation) all require NADPH and may be inhibited by DHEA and structural analogs as a result of a lowering of the NADPH cellular pool. Results obtained by others with fibroblasts and lymphocytes from individuals with the Mediterranean variant of G6PDH deficiency also indicate that a reduction in the NADPH cellular pool confers resistance to benzo(a)pyrene. Preliminary data suggest that food restriction may depress G6PDH levels and this may contribute to the tumor preventive effect of underfeeding.

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A series of studies in experimental animals have shown anticarcinogenic activity of DHEA.
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From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [287]

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Authors: Schwartz, A. G., Pashko, L., & Whitcomb, J. M.
Affiliations: Temple University (US)
Venue: Toxicologic Pathology
Publisher: SAGE Publications
Published: 1986-04
Volume: 14
Issue: 3
Pages: 357-362
ISSN: 0192-6233 (ISSN-L)
1533-1601
DOI: 10.1177/019262338601400312
OpenAlex: W2045154771
Cited by: 101
References: 43
Citations by year: 2025: 1 · 2024: 1 · 2022: 4 · 2018: 2 · 2017: 7 · 2016: 3 · 2015: 1 · 2013: 2 · 2012: 4
FWCI: 0.54
Type: journal article
Language: en
Open access: closed
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Toxicologic Pathology (publishedVersion)
PubMed (publishedVersion)
Funders: American Cancer Society
National Institutes of Health
National Cancer Institute (CA-12227, CA-14661)
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
Keywords: dehydroepiandrosterone, glucose-6-phosphate dehydrogenase, NADPH depletion, tumor chemoprevention, breast cancer, lung cancer, colon cancer, skin carcinogenesis, papilloma, 7,12-dimethylbenz(a)anthracene, tissue plasminogen activator, mixed function oxidase, superoxide production, benzo[a]pyrene, dietary restriction, underfeeding, adrenal steroids
MeSH terms: Animals, Energy Intake, Dehydroepiandrosterone, Glucosephosphate Dehydrogenase, Neoplasms, Experimental, Obesity, Steroids, Superoxides, Mice, Rats

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Inhibition of tumor development by dehydroepiandrosterone and related steroids.

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