Herbal/hormonal dietary supplement possibly associated with prostate cancer progression.
BACKGROUND
Patients seek herbal/hormonal dietary supplements (HHDS) to prevent and/or solve health and aging issues. After two men developed an unusual course of clinically aggressive prostate cancer within months of starting daily consumption of the same HHDS product, we investigated the effect of this product on prostate cancer progression.


METHODS
We evaluated serum levels of total testosterone, luteinizing hormone, and follicle-stimulating hormone and screened prostate biopsy and metastatic specimens for androgen receptor protein expression and mutations. We did hormone analyses and capillary electrophoresis. We tested the effect of the HHDS product on androgen receptor-negative (DU-145 and PC-3) and androgen receptor-positive (LNCaP) human prostate cancer cell lines.


RESULTS
Both patients had low hormone levels. The androgen receptor was expressed in all primary and metastatic prostate cancer tissues and no mutations were identified. Hormone analysis revealed that the HHDS contained testosterone and estradiol. The HHDS product was a more potent dose-dependent stimulator of cancer cell growth than testosterone both in androgen receptor-negative and receptor-positive cell lines. Blocking experiments with increasing concentrations of bicalutamide did not prevent the HHDS product-stimulated growth. We filed an adverse event report with the Food and Drug Administration who issued a warning letter. The manufacturer responded by removing this HHDS product from the market.


CONCLUSIONS
The HHDS product contained one or more endocrinologically active tumor-promoting components that had cellular androgen receptor status-independent activity. The HHDS product exhibited potent prostate cancer growth stimulatory activity that was more powerful than that of testosterone, independent of the androgen-receptor status of prostate cancer cells, and resistant to antiandrogen blockade.
Shariat
Shahrokh F
SF
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9110, USA. Shahrokh.Shariat@UTSouthwestern.edu
Lamb
Dolores J
DJ
Iyengar
Radha G
RG
Roehrborn
Claus G
CG
Slawin
Kevin M
KM
D000368:Aged; D000728:Androgens / Q000009:adverse effects*; D045744:Cell Line, Tumor; D019587:Dietary Supplements / Q000009:adverse effects*; D018450:Disease Progression; D006801:Humans; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000209:etiology / Q000503:physiopathology*; D011944:Receptors, Androgen / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
D000728:Androgens; D011944:Receptors, Androgen; D013739:Testosterone