Saw palmetto alters nuclear measurements reflecting DNA content in men with symptomatic BPH: evidence for a possible molecular mechanism.
OBJECTIVE
To examine the nuclear chromatin characteristics of epithelial cells, looking for an SPHB-mediated effect on nuclear DNA structure and organization. Saw palmetto herbal blend (SPHB) causes contraction of prostate epithelial cells and suppression of tissue dihydrotestosterone levels in men with symptomatic benign prostatic hyperplasia, but a fundamental mechanism remains unknown.


METHODS
A 6-month randomized trial, comparing prostatic tissue of men treated with SPHB (n = 20) or placebo (n = 20), was performed. At baseline, the two groups were similar in age (65 versus 64 years), symptoms (International Prostate Symptom Score 18 versus 17), uroflow (maximal urinary flow rate 10 versus 11 mL/s), prostate volume (59 versus 58 cm(3)), prostate-specific antigen (4.2 versus 2.7 ng/mL), and percentage of epithelium (17% versus 16%). Prostatic tissue was obtained by sextant biopsy before and after treatment. Five-micron sections were Feulgen stained and quantitatively analyzed using the AutoCyte QUIC-DNA imaging system. Images were captured from 200 randomly selected epithelial cell nuclei, and 60 nuclear morphometric descriptors (NMDs) (eg, size, shape, DNA content, and textural features) were determined for each nucleus. Logistic regression analysis was used to assess the differences in the variances of the NMDs between the treated and untreated prostate epithelial cells.


RESULTS
At baseline, the SPHB and placebo groups had similar NMD values. After 6 months of placebo, no significant change from baseline was found in the NMDs. However, after 6 months of SPHB, 25 of the 60 NMDs were significantly different compared with baseline, and a multivariate model for predicting treatment effect using 4 of the 25 was created (P <0.001). The multivariate model had an area under the receiver operating characteristic curve of 94% and an accuracy of 85%.


CONCLUSIONS
Six months of SPHB treatment appears to alter the DNA chromatin structure and organization in prostate epithelial cells. Thus, a possible molecular basis for tissue changes and therapeutic effect of the compound is suggested.
Veltri
Robert W
RW
Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Marks
Leonard S
LS
Miller
M Craig
MC
Bales
Wes D
WD
Fan
John
J
Macairan
Maria Luz
ML
Epstein
Jonathan I
JI
Partin
Alan W
AW
D000368:Aged; D000726:Androgen Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D002467:Cell Nucleus / Q000737:chemistry* / Q000187:drug effects; D002843:Chromatin / Q000737:chemistry / Q000187:drug effects; D004247:DNA / Q000032:analysis* / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism; D004311:Double-Blind Method; D004847:Epithelial Cells / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D007620:Karyometry / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D010919:Placebos; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011467:Prostate / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012372:ROC Curve; D028024:Serenoa; D016896:Treatment Outcome
D000726:Androgen Antagonists; D002843:Chromatin; D010919:Placebos; D010936:Plant Extracts; D013196:Dihydrotestosterone; D004247:DNA; C040972:saw palmetto extract