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


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.


CONCLUSIONS
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.
Baron
Antonella
A
Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy.
Mancini
Mariangela
M
Caldwell
Elizabeth
E
Cabrelle
Anna
A
Bernardi
Paolo
P
Pagano
Francesco
F
D017209:Apoptosis / Q000187:drug effects*; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects; D000083162:Mitochondrial Permeability Transition Pore; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D028024:Serenoa; D014407:Tumor Cells, Cultured
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010936:Plant Extracts; D045304:Cytochromes c