Dehydroepiandrosterone and Structural Analogs: A New Class of Cancer Chemopreventive Agents

Abstract

Over the past several years, several therapeutic effects of dehydroepiandrosterone (DHEA) in laboratory mice and rats have been demonstrated. These include cancer preventive, possible antiautoimmune, and antiatherogenic effects as well as antiobesity and antidiabetic activities. However, certain simplicity in the mechanism of the action of the DHEA class of steroids is now beginning to emerge. The well-documented capacity of DHEA to inhibit mammalian glucose-6-phosphate dehydrogenase (G6PDH)—the rate limiting enzyme in the pentose phosphate pathway, a major source of cytosolic NADPH—now appears central to the mechanism of the cancer preventive action of this steroid. Several laboratories have undertaken determinations of DHEAS plasma levels in women with breast cancer and in matched controls. The predominance of evidence in these case-control studies suggests that the women with breast cancer have subnormal DHEAS plasma concentrations. However, as in all case-control studies, it is uncertain whether the presence of the measured abnormality proceeds or is a consequence of the disease. © 1988 Academic Press Inc.