Involvement of human beta-defensin-2 in regulation of malignant potential of cultured human melanoma cells

• Видавець: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
• Дата: 2014
• Автори: Gerashchenko, O., Zhuravel, E., Skachkova, O., Khranovska, N., Pushkarev, V., Pogrebnoy, P., Soldatkina, M.
• Формат: Стаття
• Мова: English
• Опубліковано: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2014
• Назва видання: Experimental Oncology
• Теми: Original contributions
• Онлайн доступ: http://dspace.nbuv.gov.ua/handle/123456789/145313
• Цитувати: Involvement of human beta-defensin-2 in regulation of malignant potential of cultured human melanoma cells / O. Gerashchenko, E. Zhuravel, O. Skachkova, N. Khranovska, V. Pushkarev, P. Pogrebnoy, M. Soldatkina // Experimental Oncology. — 2014. — Т. 36, № 1. — С. 17-23. — Бібліогр.: 35 назв. — англ.

Background and Aim: 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 p21WAF1 expression, downregulation of cyclin D1 and cyclin E resulting in cell cycle arrest at G1/S checkpoint. Conclusion: 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 p21WAF1 expression and activation of pRB. Key Words: human beta-defensin-2, melanoma, proliferation, viability, cell cycle, B-Raf, anchorage-independent growth.