title: Involvement of human beta-defensin-2 in regulation of malignant potential of cultured human melanoma cells.
abstract: OBJECTIVE
  Human beta-defensin-2 (hBD-2) is an antimicrobial cationic peptide capable to control human carcinoma cell growth via cell cycle regulation. The present study was aimed on determination of hBD-2 influence on the growth patterns and malignant potential of cultured human melanoma cells.
  
  
  METHODS
  The study was performed on cultured human melanoma cells of mel Z and mel Is lines treated with recombinant hBD-2 (rec-hBD-2); cell viability, proliferation, cell cycle distribution, and anchorage-independent growth were analyzed using MTT test, direct cell counting, flow cytometry, and colony forming assay respectively. Expression and/or phosphorylation levels of proteins involved in cell cycle control were evaluated by Western blotting.
  
  
  RESULTS
  The treatment of mel Z and mel Is cells with rec-hBD-2 in a concentration range of 100-1000 nM resulted in a concentration-dependent suppression of cell proliferation, viability, and colony forming activity. It has been shown that rec-hBD-2 exerts its growth suppression effects via significant downregulation of B-Raf expression, activation of pRB and upregulation of p21(WAF1) expression, downregulation of cyclin D1 and cyclin E resulting in cell cycle arrest at G1/S checkpoint.
  
  
  CONCLUSIONS
  According to obtained results, hBD-2 exerts its growth suppression effect toward human melanoma cells via downregulation of B-Raf, cyclin D1 and cyclin E expression, upregulation of p21(WAF1) expression and activation of pRB.
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
authors.forename: O
authors.initials: O
authors.lastname: Gerashchenko
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
authors.forename: E
authors.initials: E
authors.lastname: Zhuravel
authors.affiliation: National Cancer Institute MPH of Ukraine, Kyiv 03022, Ukraine.
authors.forename: O
authors.initials: O
authors.lastname: Skachkova
authors.affiliation: National Cancer Institute MPH of Ukraine, Kyiv 03022, Ukraine.
authors.forename: N
authors.initials: N
authors.lastname: Khranovska
authors.affiliation: Institute of Endocrinology and Metabolism, AMS of Ukraine, Kyiv, Ukraine.
authors.forename: V
authors.initials: V
authors.lastname: Pushkarev
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
authors.forename: P
authors.initials: P
authors.lastname: Pogrebnoy
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
authors.forename: M
authors.initials: M
authors.lastname: Soldatkina
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D019938:Cyclin D1 / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000096:biosynthesis; D023083:beta-Defensins / Q000235:genetics*
chemical_list: D023181:Antimicrobial Cationic Peptides; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C106641:DEFB4A protein, human; D023083:beta-Defensins; D019938:Cyclin D1; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf