Serenoa repens and prostatic cancer

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BJU Int. 2004 Apr;93(6):751-6. Updated meta-analysis of clinical trials of

Serenoa repens extract in the treatment of symptomatic benign prostatic

hyperplasia. Boyle P, Robertson C, Lowe F, Roehrborn C. Department of

Epidemiology and Biostatistics, European Institute of Oncology, via Ripamonti

435, 20141 Milan, Italy. director OBJECTIVES: To determine, by

analysing all available clinical trial data, the clinical efficacy against

placebo of

an extract from the fruit of the American dwarf palm tree, Serenoa repens

(Permixon, Pierre Fabre Medicament, Castres, France), as there is controversy

about the use of phytotherapeutic agents in men with lower urinary tract

symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH).

METHODS: All clinical trial data published on Permixon, comprising 14

randomized clinical trials and three open-label trials, involving 4280 patients,

were analysed. These trials were of different size (22-1100 patients) and

duration (21-720 days). The peak urinary flow rate and nocturia were the two

common endpoints. The statistical analysis was based on a random-effects

meta-analysis. RESULTS: Permixon was associated with a mean (sem)

reduction in the International Prostate Symptom Score (IPSS) of 4.78 (0.41).

The mean placebo effect on peak urinary flow rate was an increase of 1.20

(0.49) mL/s. The estimated effect of Permixon was a further increase of 1.02

(0.50) mL/s (P = 0.042). Placebo was associated with a reduction in the mean

number of nocturnal voids of 0.63 (0.14); there was a further reduction

attributable to Permixon of 0.38 (0.07) (P < 0.001). There was some

heterogeneity among the studies for nocturia; one over 2 years involving 396

patients and showing no difference between placebo and Permixon had a large

effect on the results. CONCLUSIONS: This meta-analysis of all available

published trials of Permixon for treating men with BPH showed a significant

improvement in peak flow rate and reduction in nocturia above placebo, and a 5-

point reduction in the IPSS. Publication Types: Meta-Analysis PMID: 15049985

[PubMed - indexed for MEDLINE]

 

Int J Cancer. 2004 Jul 10;110(5):641-51. Inhibitory effects of evodiamine on the

growth of human prostate cancer cell line LNCaP. Kan SF, Huang WJ, Lin LC,

Wang PS. Department of Physiology, School of Medicine, National Yang-Ming

University, Taipei, Taiwan, Republic of China. Evodiamine, isolated from a

Chinese herbal drug named Wu-Chu-Yu, possesses many biological functions.

Recently, it has been reported that Wu-Chu-Yu exerts an antiproliferative effect

on several cancers. Prostate carcinoma initially occurs as an androgen-

dependent tumor and is the second leading cause of cancer death in American

males. In the present study, the effect of evodiamine on the growth of androgen-

dependent prostate cancer cell line LNCaP in vitro was examined. Based on [3-

(4,5-dimethylthiazol-2-yle)2,5-diphenyltetrazolium bromide] (MTT) assay,

evodiamine significantly inhibited the growth of LNCaP cells in a concentration-

dependent manner. A significant and concentration-dependent inhibitory effect

of evodiamine on LNCaP cell growth was observed at 24 hr and persisted for 96

hr. The examination of lactate dehydrogenase (LDH) assay showed that the

cytotoxic effects of evodiamine on LNCaP cells were concentration dependent.

Furthermore, we examined the influences of evodiamine on cell death and cell

cycle. The flow cytometric analysis of evodiamine-treated cells indicated a

block of G2/M phase and an elevated level of DNA fragmentation. The G2/M

arrest reached a maximum at 24 hr after evodiamine treatment. The G2/M

arrest was accompanied by an elevated p34(cdc2) kinase activity and an

increase in the protein expression of cyclin B1 and phosphorylated form of

p34(cdc2) (Thr 161). Examination of TUNEL showed that evodiamine-induced

apoptosis was observed at 24 hr and extended for 72 hr. Evodiamine elevated

caspase-3, and caspase-9 activities and the processing of caspase-3 and

caspase-9. These results suggested that evodiamine inhibits the growth of

prostate cancer cell line, LNCaP, through an accumulation of cell cycle at

G2/M phase and an induction of apoptosis. Copyright 2004 Wiley-Liss,

Inc.PMID: 15146552 [PubMed - in process]

 

J Med Chem. 2004 May 6;47(10):2430-40. Discovery of embelin as a cell-

permeable, small-molecular weight inhibitor of XIAP through structure-based

computational screening of a traditional herbal medicine three-dimensional

structure database. Nikolovska-Coleska Z, Xu L, Hu Z, Tomita Y, Li P, Roller

PP, Wang R, Fang X, Guo R, Zhang M, Lippman ME, Yang D, Wang S.

University of Michigan Comprehensive Cancer Center, Departments of Internal

Medicine and Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan

48109-0934, USA. The X-linked inhibitor of apoptosis (XIAP) is a promising new

molecular target for the design of novel anticancer drugs aiming at overcoming

apoptosis-resistance of cancer cells to chemotherapeutic agents and radiation

therapy. Recent studies demonstrated that the BIR3 domain of XIAP where

caspase-9 and Smac proteins bind is an attractive site for designing small-

molecule inhibitors of XIAP. Through computational structure-based screening

of an in-house traditional herbal medicine three-dimensional structure database

of 8221 individual natural products, followed by biochemical testing of selected

candidate compounds, we discovered embelin from the Japanese Ardisia herb

as a small-molecular weight inhibitor that binds to the XIAP BIR3 domain. We

showed that embelin binds to the XIAP BIR3 protein with an affinity similar to

that of the natural Smac peptide using a fluorescence polarization-based

binding assay. Our NMR analysis further conclusively confirmed that embelin

interacts with several crucial residues in the XIAP BIR3 domain with which

Smac and caspsase-9 bind. Embelin inhibits cell growth, induces apoptosis,

and activates caspase-9 in prostate cancer cells with high levels of XIAP, but

has a minimal effect on normal prostate epithelial and fibroblast cells with low

levels of XIAP. In stably XIAP-transfected Jurkat cells, embelin effectively

overcomes the protective effect of XIAP to apoptosis and enhances the

etoposide-induced apoptosis and has a minimal effect in Jurkat cells

transfected with vector control. Taken together, our results showed that embelin

is a fairly potent, nonpeptidic, cell-permeable, small-molecule inhibitor of

XIAP

and represents a promising lead compound for designing an entirely new class

of anticancer agents that target the BIR3 domain of XIAP. PMID: 15115387

[PubMed - in process]

 

Prostate. 2004 May 15;59(3):260-7. Modulation of anti-adhesion molecule MUC-

1 is associated with arctiin-induced growth inhibition in PC-3 cells. Huang DM,

Guh JH, Chueh SC, Teng CM. Pharmacological Institute, College of Medicine,

National Taiwan University, Taipei, Taiwan. BACKGROUND: Lignans have

been reported to possess anti-tumor activity in various cancer cells. However,

their anticancer effects in human prostate cancer have not been well

established. Here, we examine the effect of arctiin, a lignan compound, on

growth regulation in prostate cancer PC-3 cells. We postulated that arctiin

modulates the attachment/detachment of PC-3 cells and we investigated the

role of arctiin on MUC-1 expression. METHODS: The effect of arctiin on PC-3

cell growth was examined using an MTT assay method and cell number was

calculated by means of a standard regression line. The expressions of MUC-1

and integrins alpha2, alpha5, and beta1 were detected using FACScan flow

cytometric analysis. Levels of MUC-1 mRNA were determined using reverse

transcriptase PCR (RT-PCR). RESULTS: Treatment of PC-3 cells with arctiin

decreased the cell number in a concentration- and time-dependent manner in

serum-containing condition. Arctiin preferentially induced cell detachment, but

did not have anti-proliferation or cytotoxic effects in PC-3 cells. The arctiin-

induced effect was inhibited by cycloheximide, indicating that protein synthesis

was required. FACScan flow cytometric analysis demonstrated that arctiin

increased the expression of the anti-adhesion mucin MUC-1, but did not affect

integrin expression in PC-3 cells. The arctiin-induced increase in MUC-1 protein

expression was due to up-regulation of mRNA, as revealed by RT-PCR

analysis. CONCLUSIONS: Arctiin significantly induces cell detachment and

decreases the cell numbers via the up-regulation of MUC-1 mRNA and protein

in PC-3 cells. Copyright 2004 Wileey-Liss, Inc. PMID: 15042601 [PubMed -

indexed for MEDLINE]

 

Cancer Chemother Pharmacol. 2004 Mar 24 [Epub ahead of print] Rasagenthi

lehyam (RL) a novel complementary and alternative medicine for prostate

cancer. Ranga RS, Girija R, Nur-E-Alam M, Sathishkumar S, Akbarsha MA,

Thirugnanam S, Rohr J, Ahmed MM, Chendil D. Department of Clinical

Sciences, College of Health Sciences, University of Kentucky, Room No 209D,

900 South Limestone Street, KY 40536-0200, Lexington, USA. PURPOSE.

The use of complementary and alternative medicine (CAM) in cancer has been

increasing. The therapeutic modalities which originated from India, viz.,

Ayurveda and Siddha, have phytotherapy as their fundamental basis and,

therefore, produce few side effects. They are among the most ancient medicinal

systems and are still being practiced in India and elsewhere, to cure cancer

and other diseases. Many Siddha practitioners in the southern parts of India

prescribe rasagenthi lehyam (RL) as a drug for cancer. RL contains 38 different

botanicals, many of which have been shown to possess therapeutic efficacy,

and 8 inorganic compounds, all prepared into a paste in a palm sugar and hen's

egg base. The efficacy of RL in killing prostate cancer cells in vitro was

investigated in this study to determine whether RL could be recommended as a

CAM for prostate cancer. METHODS. In order to scientifically validate the

anticancer activity of RL on prostate cancer, a methanolic extract of RL was

serially extracted with four organic solvents, and the extracts were tested for

clonogenic inhibition and induction of apoptosis in PC-3 prostate cancer cells,

with and without irradiation. n-Hexane, ethyl acetate and chloroform extracts of

RL effectively killed PC-3 cells. RESULTS. The IC(50) values of n-hexane, ethyl

acetate and chloroform extracts of RL were 3.84 microg/ml, 3.68 microg/ml and

75 ng/ml, respectively. All three extracts induced apoptosis in PC-3 cells.

Further, all the three extracts when combined with radiation, caused enhanced

effect on killing of PC-3 cells. Among the three extracts, the chloroform

extract

showed the most significant radiation-sensitizing effect. CONCLUSION. RL,

either in its original formulation prepared under strict quality control or its

chloroform extract, could potentially be an alternative medicine for prostate

cancer, and also a sensitizing agent in the context of radiation therapy for

prostate cancer, as a complementary medicine. A more directed study could

lead to the identification of the active principle(s) in the chloroform extract

of RL

for use in prostate cancer therapy. PMID: 15042313 [PubMed - as supplied by

publisher]

 

Hinyokika Kiyo. 2004 Mar;50(3):215-7. [Licorice of 'shakuyaku kanzou tou'

induced pseudoaldosteronism] [Article in Japanese] Kanda H, Sakurai M,

Arima K. Department of Urology, Matsusaka Municipal Hospital. We report a

case of pseudoaldosteronism induced by licorice in a kampo medication

'Shakuyaku Kanzou Tou' that was diagnosed after relief of urinary retention due

to benign prostatic hypertrophy (BPH). A-71-year-old man was admitted to our

hospital due to urinary retention. At admission, he had hypertension and leg

edema, but serum potassium was in the normal range. One day after

admission, hypokalemia was recognized. He was taking " Shakuyaku Kanzou

Tou " , a Chinese medicine that contains glycyrrhizin. So we suspected

pseudoaldosteronism and had him stop taking it. Computed tomography did not

reveal any adrenal tumor. Plasma rennin activity and aldosterone level were

suppressed. Gradually, hypertension and leg edema improved and serum

potassium became within the normal range. We diagnosed the case as

pseudoaldosteronism induced by licorice of 'Shakuyaku Kanzou Tou'. Since we

suspected BPH to be the cause of urinary retention, we performed transurethral

resection of prostate. After surgery, he was able to void smoothly. PMID:

15148778 [PubMed - in process]

 

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