title: The impaired viability of prostate cancer cell lines by the recombinant plant kallikrein inhibitor.
abstract: BACKGROUND
  Kallikreins play a pivotal role in establishing prostate cancer.
  
  
  RESULTS
  In contrast to the classical Kunitz plant inhibitor SbTI, the recombinant kallikrein inhibitor (rBbKIm) led to prostate cancer cell death, whereas fibroblast viability was not affected.
  
  
  CONCLUSIONS
  rBbKIm shows selective cytotoxic effect and angiogenesis inhibition against prostate cancer cells.
  
  
  CONCLUSIONS
  New actions of rBbKIm may contribute to understanding the mechanisms of prostate cancer. Prostate cancer is the most common type of cancer, and kallikreins play an important role in the establishment of this disease. rBbKIm is the recombinant Bauhinia bauhinioides kallikreins inhibitor that was modified to include the RGD/RGE motifs of the inhibitor BrTI from Bauhinia rufa. This work reports the effects of rBbKIm on DU145 and PC3 prostate cancer cell lines. rBbKIm inhibited the cell viability of DU145 and PC3 cells but did not affect the viability of fibroblasts. rBbKIm caused an arrest of the PC3 cell cycle at the G0/G1 and G2/M phases but did not affect the DU145 cell cycle, although rBbKIm triggers apoptosis and cytochrome c release into the cytosol of both cell types. The differences in caspase activation were observed because rBbKIm treatment promoted activation of caspase-3 in DU145 cells, whereas caspase-9 but not caspase-3 was activated in PC3 cells. Because angiogenesis is important to the development of a tumor, the effect of rBbKIm in this process was also analyzed, and an inhibition of 49% was observed in in vitro endothelial cell capillary-like tube network formation. In summary, we demonstrated that different properties of the protease inhibitor rBbKIm may be explored for investigating the androgen-independent prostate cancer cell lines PC3 and DU145.
authors.affiliation: Departments of Biochemistry, Universidade Federal de São Paulo-Escola Paulista de Medicina, 04044-020, São Paulo, Brazil.
authors.forename: Joana Gasperazzo
authors.initials: JG
authors.lastname: Ferreira
authors.forename: Paula Malloy Motta
authors.initials: PM
authors.lastname: Diniz
authors.forename: Cláudia Alessandra
authors.initials: CA
authors.lastname: Andrade de Paula
authors.forename: Yara Aparecida
authors.initials: YA
authors.lastname: Lobo
authors.forename: Edgar Julian
authors.initials: EJ
authors.lastname: Paredes-Gamero
authors.forename: Thaysa
authors.initials: T
authors.lastname: Paschoalin
authors.forename: Amanda
authors.initials: A
authors.lastname: Nogueira-Pedro
authors.forename: Paloma Korehisa
authors.initials: PK
authors.lastname: Maza
authors.forename: Marcos Sergio
authors.initials: MS
authors.lastname: Toledo
authors.forename: Erika
authors.initials: E
authors.lastname: Suzuki
authors.forename: Maria Luiza Vilela
authors.initials: ML
authors.lastname: Oliva
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020013:Calcium Signaling; D053148:Caspase 3; D053453:Caspase 9 / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival / Q000187:drug effects*; D045304:Cytochromes c / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007610:Kallikreins / Q000037:antagonists & inhibitors*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010940:Plant Proteins / Q000494:pharmacology*; D011471:Prostatic Neoplasms; D011994:Recombinant Proteins / Q000494:pharmacology; D014360:Trypsin Inhibitor, Kunitz Soybean / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; C434623:BbKI protein, Bauhinia bauhinioides; D008070:Lipopolysaccharides; D010940:Plant Proteins; D011994:Recombinant Proteins; D045304:Cytochromes c; D014360:Trypsin Inhibitor, Kunitz Soybean; D007610:Kallikreins; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9
keywords: Angiogenesis; Blood Coagulation Factors; Cancer Chemoprevention; Cell Adhesion; Cell Death; Cell Migration; Enzyme Inhibitors; Flow Cytometry; Kallikrein; Protein Sequence