title: Serenoa repens extract targets mitochondria and activates the intrinsic apoptotic pathway in human prostate cancer cells.
abstract: 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.
authors.affiliation: Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Baron
authors.forename: Mariangela
authors.initials: M
authors.lastname: Mancini
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Caldwell
authors.forename: Anna
authors.initials: A
authors.lastname: Cabrelle
authors.forename: Paolo
authors.initials: P
authors.lastname: Bernardi
authors.forename: Francesco
authors.initials: F
authors.lastname: Pagano
mesh_terms: 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
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010936:Plant Extracts; D045304:Cytochromes c