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

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://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
May 2009
275 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