Serenoa repens extract targets mitochondria and activates the intrinsic apoptotic pathway in human prostate cancer cells.

Authors:
Antonella Baron
Antonella Baron
Venetian Institute of Molecular Medicine
Mariangela Mancini
Mariangela Mancini
University of Padova
Italy
Elizabeth Caldwell
Elizabeth Caldwell
Princess Alexandra Hospital
Anna Cabrelle
Anna Cabrelle
Medical School
Paolo Bernardi
Paolo Bernardi
University of Padova
Padova | Italy
Francesco Pagano
Francesco Pagano
Catholic University of Medicine
Italy

BJU Int 2009 May 14;103(9):1275-83. Epub 2009 Jan 14.

Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy.

Objective: To investigate the effects of Serenoa repens extract (Sr) in human PC3 and LNCaP prostate cancer and MCF7 breast cancer cells, with specific emphasis on the role of the mitochondrial apoptotic pathway, as the molecular pathway through which Sr, a natural product of plant origin, induces death of prostate cancer cells in culture is still unknown.

Material And Methods: Cellular and mitochondrial structure and function, and the cell cycle, were analysed using light, electron and fluorescence microscopy, spectrophotometry and flow cytometry. Apoptosis was evaluated using biochemical and cytohistochemical methods.

Results: Cells treated with Sr underwent massive vacuolization and cytosolic condensation, followed by cell death only in the prostate lines. Within minutes of adding Sr to prostate cells, it caused opening of the permeability transition pore (PTP), which led to complete mitochondrial depolarization within 2 h, and to the appearance of small, pycnotic mitochondria. Release of cytochrome c and SMAC/Diablo to the cytosol was detectable after 4 h of treatment, while caspase 9 activation and poly(ADP-ribose) polymerase 1 cleavage occurred at 16 h, followed by appearance of a sub-G1 peak and apoptosis at 24 h.

Conclusion: Sr selectively induces apoptotic cell death of prostate cancer cells through the intrinsic pathway, and activation of the mitochondrial PTP might play a central role in this process.

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1464-410X.2008.08266.xDOI Listing
May 2009
60 Reads

Publication Analysis

Top Keywords

cancer cells
16
prostate cancer
16
death prostate
12
serenoa repens
8
cell death
8
apoptotic pathway
8
repens extract
8
prostate
6
cells
6
cancer
5
lines minutes
4
minutes adding
4
prostate lines
4
cycle analysed
4
vacuolization cytosolic
4
cytosolic condensation
4
condensation cell
4
adding prostate
4
prostate cells
4
transition pore
4

Similar Publications

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

Anticancer Res 2007 Mar-Apr;27(2):873-81

University Hospital Zurich, Department of Internal Medicine, Institute for Complementary Medicine, Rämistrasse 100, 8091 Zurich, Switzerland.

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. Read More

View Article
May 2007

Lipido-sterolic extract of Serenoa repens (LSESr, Permixon) treatment affects human prostate cancer cell membrane organization.

J Cell Physiol 2009 Apr;219(1):69-76

Department Experimental Medicine, Sapienza University of Rome, Rome, Italy.

The molecular mechanism by which the lipido-sterolic extract of Serenoa repens (LSESr, Permixon) affects prostate cells remains to be fully elucidated. In androgen-independent PC3 prostate cancer cells, the LSESr-induced effects on proliferation and apoptosis were evaluated by counting cells and using a FACScan cytofluorimeter. PC3 cells were stained with JC-1 dye to detect mitochondrial membrane potential. Read More

View Article
April 2009

Riluzole induces apoptotic cell death in human prostate cancer cells via endoplasmic reticulum stress.

Anticancer Res 2009 Jun;29(6):2195-204

Department of Anatomy and Cell Biology, Division of Life Sciences, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.

Background: Ion channel modulators have been previously associated with cell proliferation and cell death in human cancer cell lines.

Materials And Methods: The effects of riluzole, an ion channel modulator, on cell proliferation, apoptosis and the apoptotic pathway in the LNCaP and C4-2 prostate cancer cell lines were investigated.

Results: Riluzole inhibited DNA synthesis and increased apoptotic cells in both cell lines. Read More

View Article
June 2009

Induction of apoptotic cell death by a ceramide analog in PC-3 prostate cancer cells.

Arch Pharm Res 2006 Dec;29(12):1140-6

College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea.

Ceramide analogs are potential chemotherapeutic agents. We report that a ceramide analog induces apoptosis in human prostate cancer cells. The ceramide analog induced cell death through an apoptotic mechanism, which was demonstrated by DNA fragmentation, the cleavage of poly ADP ribose polymerase (PARP), and a loss of membrane asymmetry. Read More

View Article
December 2006