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Letters |
Departments of,
1
Nutritional Sciences, and,
2
Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada M5S 3E2
3
Department of Pathology, and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5
a Address correspondence to this author at: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave., Toronto, Ontario, Canada M5G 1X5. Fax 416-586-8628; e-mail ediamandis{at}mtsinai.on.ca
To the Editor:
Flavonoids and other polyphenolic natural compounds have attracted much attention as candidate cancer preventive and anticarcinogenic agents, as well as antiatherogenic and antioxidant compounds (1). Although the public now consumes these compounds in substantial amounts from dietary sources, food supplements, and more recently, as "nutraceutical" tablets, their actual mode of action is not fully defined. The most compelling hypotheses correlate the biological action of flavonoids to their ability to mimic natural estrogens (2)(3) such as estradiol, or to act as antioxidants (4). Indeed, genistein, a natural soy isoflavone, is among the most potent known phytoestrogens. The ability of flavonoids to act as androgen mimics or antiandrogens has attracted much less attention. Recently, we showed that apigenin, a natural flavone found in chamomile, olive leaves, and other plant sources, has potent progestational activity (5).
We have examined the possible antiandrogenic activity of genistein
using the steroid hormone receptor-positive breast cancer cell line
BT-474. This cell line, when stimulated by dihydrotestosterone (DHT),
produces prostate-specific antigen (PSA), which is then secreted into
the tissue culture supernatant and can be measured quantitatively by
immunoassay. Details of this system are given elsewhere (5).
To study the antiandrogenic activity, the cells were first exposed to
the putative antiandrogen (10-5 to
10-8 mol/L) for 1 h and then stimulated
with DHT (10-9 mol/L). Controls with only
antiandrogen or only DHT were included in all experiments. Nilutamide
was used as a control antiandrogen. Our data (Fig. 1
) clearly demonstrate the potent antiandrogenic activity of
genistein, which is dose-dependent and is detectable down to
10-7 mol/L. Quercetin and several other
flavonoids tested were devoid of such activity (data not shown).
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These data clearly demonstrate for the first time that genistein exhibits potent antiandrogenic activity in addition to its well-established estrogenic activity. Indeed, the therapeutic potential of this compound in prostate cancer patients may be related to its combined estrogenic and antiandrogenic properties. It will be interesting to examine large numbers of natural compounds for antiandrogenic activity, which may qualify them as candidate therapeutic and preventive agents for prostate, breast, and possibly other hormonally dependent cancers.
References
The following articles in journals at HighWire Press have cited this article:
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  N. E. Gray, X. Liu, R. Choi, M. R. Blackman, and J. T. Arnold Endocrine-Immune-Paracrine Interactions in Prostate Cells as Targeted by Phytomedicines Cancer Prevention Research, February 1, 2009; 2(2): 134 - 142. [Abstract] [Full Text] [PDF]
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), quercetin (
), or nilutamide
(
)], blocker and steroid (DHT), or steroid alone. Blockers were
tested at concentrations of 10-5 to 10-8
mol/L, and DHT was used at 10-9 mol/L. For the cells
stimulated with blocker and steroid, the blocker was added first and
incubated for 1 h; the cells were then stimulated with steroid.
Alcohol was used as a negative control. The plates were then incubated
for 7 days, at which time the tissue supernatants were harvested. The
supernatants were then analyzed quantitatively for PSA.
Blocking activity was assessed by dividing the amount of PSA produced
by the candidate blocker + steroid and by steroid alone and multiplying
by 100. None of the candidate blockers induced any PSA production when
added alone.