Evaluation of cell death caused by an ethanolic extract of Serenoae repentis fructus (Prostasan) on human carcinoma cell lines.

BACKGROUND Phytotherapy is a third approach for treating lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH). The lipido-sterolic extract of the fruit of Serenoa repens is one of the more widely used phytotherapeutic agents in this regard. MATERIALS AND METHODS The effect of an ethanolic extract of S. repens (10-1000 microg/ml) was tested in hormone-sensitive LNCaP, MCF-7 and hormone-insensitive DU 145, MDA MB231 prostate, breast carcinoma cell lines, renal Caki-1, urinary bladder J82, colon HCT 116 and lung A 549 cancer cells. Its cell growth inhibitory and apoptosis-inducing effects were tested using WST-1 assay and flow cytometry (Annexin V/PI stain) and/or by colorimetric assay (APOPercentage assay). RESULTS The S. repens extract induced a dose-dependent antiproliferative effect on all human malignant cells tested, with GI50 values between 107 and 327 pmicro/ml. In hormone-sensitive prostate LNCaP and breast MCF-7 cell lines, the effect of extract expressed in GI50 was 2.2- and 2.5-fold more potent (p < 0.01) than in hormone-insensitive DU 145 and MDA MB231 cells. The proportion of apoptotic cells, except in A549 cells, lay between 22.5-36.3%. S. repens extract did not induce apoptosis in lung cancer A 549 cells. CONCLUSION This study showed that the antiproliferative effect exerted by the ethanolic extract of S. repens is at least triggered by induction of apoptosis. These in vitro data provide some information that may be useful for clinical use and render S. repens extract an interesting tool for new applications.

[1]  A. Farré,et al.  Serenoa repens treatment modifies bax/bcl-2 index expression and caspase-3 activity in prostatic tissue from patients with benign prostatic hyperplasia. , 2005, The Journal of urology.

[2]  R. Saller,et al.  Apoptosis of human prostate androgen-dependent and -independent carcinoma cells induced by an isopropanolic extract of black cohosh involves degradation of cytokeratin (CK) 18. , 2005, Anticancer research.

[3]  A. Senderowicz.  Targeting cell cycle and apoptosis for the treatment of human malignancies. , 2004, Current opinion in cell biology.

[4]  N. Kyprianou,et al.  Effect of permixon on human prostate cell growth: Lack of apoptotic action , 2004, The Prostate.

[5]  C. Roberts,et al.  Saw palmetto extract suppresses insulin-like growth factor-I signaling and induces stress-activated protein kinase/c-Jun N-terminal kinase phosphorylation in human prostate epithelial cells. , 2004, Endocrinology.

[6]  A. Farré,et al.  BPH and inflammation: pharmacological effects of Permixon on histological and molecular inflammatory markers. Results of a double blind pilot clinical assay. , 2003, European urology.

[7]  G. Gerber.  Phytotherapy for benign prostatic hyperplasia , 2002, Current urology reports.

[8]  P. Boyle,et al.  [Comparison of a phytotherapeutic agent (Permixon) with an alpha-blocker (Tamsulosin) in the treatment of benign prostatic hyperplasia: a 1-year randomized international study]. , 2002, Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie.

[9]  H. Nishino,et al.  Inhibitory effect of herbal remedies on 12-O-tetradecanoylphorbol-13-acetate-promoted Epstein-Barr virus early antigen activation. , 2002, Pharmacological research.

[10]  W. H. Goldmann,et al.  SAW PALMETTO BERRY EXTRACT INHIBITS CELL GROWTH AND COX‐2 EXPRESSION IN PROSTATIC CANCER CELLS , 2001, Cell biology international.

[11]  K. Iguchi,et al.  Myristoleic acid, a cytotoxic component in the extract from Serenoa repens, induces apoptosis and necrosis in human prostatic LNCaP cells , 2001, The Prostate.

[12]  H. Yamamoto,et al.  Extract from Serenoa repens suppresses the invasion activity of human urological cancer cells by inhibiting urokinase-type plasminogen activator. , 2001, Biological & pharmaceutical bulletin.

[13]  T. Wilt,et al.  Phytotherapy for benign prostatic hyperplasia , 2000, Public Health Nutrition.

[14]  C. Abbou,et al.  Induction of apoptosis and inhibition of cell proliferation by the lipido‐sterolic extract of Serenoa repens (LSESr, Permixon®) in benign prostatic hyperplasia , 2000, The Prostate.

[15]  F. Habib,et al.  The selectivity and specificity of the actions of the lipido-sterolic extract of Serenoa repens (Permixon) on the prostate. , 2000, The Journal of urology.

[16]  F. Habib,et al.  Serenoa repens (Permixon®): A 5α‐reductase types I and II inhibitor—new evidence in a coculture model of BPH , 1999, The Prostate.

[17]  John Calvin Reed.  Mechanisms of apoptosis avoidance in cancer. , 1999, Current opinion in oncology.

[18]  P. Braquet,et al.  Effect of the Lipidosterolic Extract of Serenoa repens (Permixon®) and Its Major Components on Basic Fibroblast Growth Factor-Induced Proliferation of Cultures of Human Prostate Biopsies , 1998, European Urology.

[19]  P. Braquet,et al.  Effect of the lipidic lipidosterolic extract of Serenoa repens (Permixon) on the ionophore A23187-stimulated production of leukotriene B4 (LTB4) from human polymorphonuclear neutrophils. , 1997, Prostaglandins, leukotrienes, and essential fatty acids.

[20]  M. Russo,et al.  Effects of the lipidosterolic extract of Serenoa repens (Permixon®) on human prostatic cell lines , 1996, The Prostate.

[21]  F. Hamdy,et al.  Comparison of phytotherapy (Permixon®) with finasteride in the treatment of benign prostate hyperplasia: A randomized international study of 1,098 patients , 1996, The Prostate.

[22]  N. Kyprianou,et al.  Apoptotic versus proliferative activities in human benign prostatic hyperplasia. , 1996, Human pathology.

[23]  A. Hidalgo,et al.  Mechanisms involved in the spasmolytic effect of extracts from Sabal serrulata fruit on smooth muscle. , 1996, General pharmacology.

[24]  G. Faure,et al.  Placebo-Controlled Evaluation of the Efficacy and Tolerability of Permixon® in Benign Prostatic Hyperplasia after Exclusion of Placebo Responders , 1995 .

[25]  A. Wyllie,et al.  Apoptosis is inversely related to necrosis and determines net growth in tumors bearing constitutively expressed myc, ras, and HPV oncogenes. , 1994, The American journal of pathology.

[26]  A. Sciarra,et al.  Evidence that Serenoa repens extract displays an antiestrogenic activity in prostatic tissue of benign prostatic hypertrophy patients. , 1992, European urology.