DHEA and cancer

An interesting article has been published in Steroids 2003 Jan;68(1):73-83 that correlates endogenous DHEA to anti-proliferative action on human cancer cell lines under the title "Anti-proliferative action of endogenous dehydroepiandrosterone metabolites on human cancer cell lines." by S. Yoshida et al. at Department of Gastroenterology and Hepatology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Ibaraki, Japan

Dehydroepiandrosterone (DHEA) is a naturally occurring steroid synthesized in the adrenal cortex, gonads, brain, and gastrointestinal tract, and it is known to have chemopreventive and anti-proliferative actions on tumors. These effects are considered to be induced by the inhibition of glucose-6-phosphate dehydrogenase (G6PD) and/or HMG-CoA reductase (HMGR) activities. The present study was undertaken to investigate whether endogenous DHEA metabolites, i.e. DHEA-sulfate, 7-oxygenated DHEA derivatives, androsterone, epiandrosterone, and etiocholanolone, have anti-proliferative effects on cancer cells and to clarify which enzyme, G6PD or HMGR, is responsible for growth inhibition. Growth of Hep G2, Caco-2, and HT-29 cells, evaluated by 3-[4,5-dimethylthiazol]-2yl-2,5-diphenyl tetrazolium bromide (MTT) and bromodeoxyuridine incorporation assays, was time- and dose-dependently inhibited by addition of all DHEA-related steroids we tested. In particular, the growth inhibition due to etiocholanolone was considerably greater than that caused by DHEA in all cell lines. The suppression of growth of the incubated steroids was not correlated with the inhibition of G6PD (r=-0.031, n=9, NS) or HMGR (r=0.219, n=9, NS) activities. The addition of deoxyribonucleosides or mevalonolactone to the medium did not overcome the inhibition of growth induced by DHEA or etiocholanolone, while growth suppression by DHEA was partially prevented by the addition of ribonucleosides. These results demonstrate that endogenous DHEA metabolites also have an anti-proliferative action that is not induced by inhibiting G6PD or HMGR activity alone. These non-androgenic DHEA metabolites may serve as chemopreventive or anti-proliferative therapies.

DHEA or dehydroepiandrosterone is an endogenous intermediate steroid hormone produced by the adrenal glands. DHEA is called "mother of hormones", or prohormone because DHEA is further converted to generate 50 other essential hormones such as androgens (male hormones) or estrogens (female hormones) in the cells. DHEA is the most abundant hormone in our blood, and adequate blood DHEA or DHEA-S (dehydroepiandrosterone sulfate) level is critical for many vital hormonal and metabolic functions of our body.

Unfortunately, our body produces less and less DHEA as we age, and as a result, our blood DHEA (or DHEA-S) level decreases as we get older, generally falling significantly by the age of 30, and by as much as 50% by as 40.

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