The Impaired Viability of Prostate Cancer Cell Lines by the Recombinant Plant Kallikrein Inhibitor

• Published in: The Journal of biological chemistry 2013-05, Vol.288 (19), p.13641-13654
• Main Authors: Ferreira, Joana Gasperazzo, Diniz, Paula Malloy Motta, de Paula, Cláudia Alessandra Andrade, Lobo, Yara Aparecida, Paredes-Gamero, Edgar Julian, Paschoalin, Thaysa, Nogueira-Pedro, Amanda, Maza, Paloma Korehisa, Toledo, Marcos Sergio, Suzuki, Erika, Oliva, Maria Luiza Vilela
• Format: Article
• Language: English
• Subjects: Angiogenesis; Angiogenesis Inhibitors - pharmacology; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Blood Coagulation Factors; Calcium Signaling; Cancer Chemoprevention; Caspase 3; Caspase 9 - metabolism; Cell Adhesion; Cell Adhesion - drug effects; Cell Biology; Cell Cycle Checkpoints; Cell Death; Cell Line, Tumor; Cell Migration; Cell Movement; Cell Survival - drug effects; Cytochromes c - metabolism; Enzyme Inhibitors; Fibroblasts - drug effects; Fibroblasts - physiology; Flow Cytometry; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - physiology; Humans; Hydrophobic and Hydrophilic Interactions; Kallikrein; Kallikreins - antagonists & inhibitors; Lipopolysaccharides - pharmacology; Male; Mitochondria - drug effects; Mitochondria - metabolism; Plant Proteins - pharmacology; Prostatic Neoplasms; Protein Sequence; Recombinant Proteins - pharmacology; Trypsin Inhibitor, Kunitz Soybean - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M112.404053

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. 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. Conclusion: rBbKIm shows selective cytotoxic effect and angiogenesis inhibition against prostate cancer cells. Significance: New actions of rBbKIm may contribute to understanding the mechanisms of prostate cancer.