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.

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Source
http://doi.wiley.com/10.1111/j.1464-410X.2008.08266.x
Publisher Site
http://dx.doi.org/10.1111/j.1464-410X.2008.08266.xDOI Listing

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May 2009
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References

(Supplied by CrossRef)
Prostate cancer prevention: past, present, and future
Fleshner et al.
Cancer 2007
The role of a lipido-sterolic extract of Serenoa repens in the management of lower urinary tract symptoms associated with benign prostatic hyperplasia
Gerber et al.
BJU Int 2004
Saw palmetto for benign prostatic hyperplasia
Bent et al.
N Engl J Med 2006
Is there a scientific basis for the therapeutic effects of Serenoa repens in benign prostatic hyperplasia? Mechanisms of action
Buck et al.
J Urol 2004
Myristoleic acid, a cytotoxic component in the extract from Serenoa repens, induces apoptosis and necrosis in human prostatic LNCaP cells
Iguchi et al.
Prostate 2001
Saw palmetto for the treatment of men with lower urinary tract symptoms
Gerber et al.
J Urol 2000
Saw palmetto berry extract inhibits cell growth and Cox-2 expression in prostatic cancer cells
Goldmann et al.
Cell Biol Int 2001
Effect of permixon on human prostate cell growth: lack of apoptotic action
Hill et al.
Prostate 2004
Mitochondrial energy dissipation by fatty acids. Mechanisms and implications for cell death
Bernardi et al.
Vitam Horm 2002
Mitochondria are direct targets of the lipoxygenase inhibitor MK886. A strategy for cell killing by combined treatment with MK886 and cyclooxygenase inhibitors
Gugliucci et al.
J Biol Chem 2002

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