title: Influence of ellagic acid on prostate cancer cell proliferation: a caspase-dependent pathway.
abstract: OBJECTIVE
  To evaluate the effect of allagic acid treatment on the cell viability of human prostate cancer cells.
  
  
  METHODS
  Ellagic acid (10-100 mol/L) treatment (48 h) of human prostate carcinoma PC3 cells was found to result in a dose-dependent inhibition of cell growth and apoptosis of PC3 cells as assessed by MTT assay, western blotting, flow cytometry and confocal microscopy.
  
  
  RESULTS
  We observed that ellagic acid treatment of PC3 cells resulted in a dose dependent inhibition of cell growth/cell viability. This ellagic acid caused cell growth inhibition was found to be accompanied by induction of apoptosis, as assessed by the cleavage of poly (ADP-ribose) polymerase (PARP) and morphological changes. Further, induction of apoptosis accompanied a decrease in the levels of antiapoptotic protein Bcl-2 and increase in proapoptotic protein Bax, thus shifting the Bax: Bcl-2 ratio in favor of apoptosis. Ellagic acid treatment of PC3 cells was also found to result in significant activation of caspases, as shown by the dose dependent decrease in the protein expression of procaspase-3, -6, -8 and -9. This ellagic acid-mediated induction of apoptosis was significantly (80%-90%) inhibited by the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp (OMe)-fluoromethylketone (Z-VAD-FMK). Thus these data suggested an essential role of caspases in ellagic acid-mediated apoptosis of PC3 cells.
  
  
  CONCLUSIONS
  It is tempting to suggest that consumption of tropical pigmented fruits and vegetables could be an effective strategy to combat prostate cancer.
authors.affiliation: Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Kingdom of Saudi Arabia. arshimalik@gmail.com
authors.forename: Arshi
authors.initials: A
authors.lastname: Malik
authors.forename: Sarah
authors.initials: S
authors.lastname: Afaq
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shahid
authors.forename: Kafil
authors.initials: K
authors.lastname: Akhtar
authors.forename: Abdullah
authors.initials: A
authors.lastname: Assiri
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004610:Ellagic Acid / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D004610:Ellagic Acid; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases