Human beta-defensin-2 controlS cell cycle in malignant epithelial cells: in vitro study
Aim: In the present research we analyze the mechanism of human beta-defensin-2 (hBD-2) influence on cultured malignant epithelial cell growth. Materials and Methods: The analysis of a concentration-dependent effect of recombinant hBD-2 (rec-hBD-2) on cell growth patterns and cell cycle distribution...
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| Published in: | Experimental Oncology |
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| Date: | 2011 |
| Main Authors: | , , , , , , |
| Format: | Article |
| Language: | English |
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2011
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| Online Access: | https://nasplib.isofts.kiev.ua/handle/123456789/138664 |
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| Journal Title: | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| Cite this: | Human beta-defensin-2 controlS cell cycle in malignant epithelial cells: in vitro study / E. Zhuravel, T. Shestakova, O. Efanova, Yu. Yusefovich, D. Lytvin, M. Soldatkina, P. Pogrebnoy // Experimental Oncology. — 2011. — Т. 33, № 3. — С. 114-120. — Бібліогр.: 29 назв. — англ. |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine| _version_ | 1862543793689985024 |
|---|---|
| author | Zhuravel, E. Shestakova, T. Efanova, O. Yusefovich, Yu. Kytvin, D. Soldatkina, M. Pogrebnoy, P. |
| author_facet | Zhuravel, E. Shestakova, T. Efanova, O. Yusefovich, Yu. Kytvin, D. Soldatkina, M. Pogrebnoy, P. |
| citation_txt | Human beta-defensin-2 controlS cell cycle in malignant epithelial cells: in vitro study / E. Zhuravel, T. Shestakova, O. Efanova, Yu. Yusefovich, D. Lytvin, M. Soldatkina, P. Pogrebnoy // Experimental Oncology. — 2011. — Т. 33, № 3. — С. 114-120. — Бібліогр.: 29 назв. — англ. |
| collection | DSpace DC |
| container_title | Experimental Oncology |
| description | Aim: In the present research we analyze the mechanism of human beta-defensin-2 (hBD-2) influence on cultured malignant epithelial cell growth. Materials and Methods: The analysis of a concentration-dependent effect of recombinant hBD-2 (rec-hBD-2) on cell growth patterns and cell cycle distribution has been performed in vitro with 2 cell lines (human lung adenocarcinoma A549 cells and human epidermoid carcinoma A431 cells) using MTT test, flow cytometry and direct cell counting. To study intracellular localization of hBD-2 immunocytofluorescent and immunocytochemical analyses were applied, and effect of hBD-2 on signal cascades involved in cell cycle regulation has been studied by Western blotting. Results: According to our data, rec-hBD-2 exerts a concentration-dependent effect on the viability of cultured A549 and A431 cells. It causes proproliferative effect at concentrations below 1 nM, significant suppression of cell proliferation at concentration range from 10 nM to 1 µM (p<0.05), and cell death at higher concentrations. Using flow cytometry we have demonstrated that hBD-2 dependent growth suppression is realized via cell cycle arrest at G1/S phase (p<0.05). Also, we have registered significant activation of pRB and decreased expression of Cyclin D1 in cells treated with the defensin compared to untreated control cells, while the expression of p53 remains unaffected. The study of intracellular localization of hBD-2 in these cells has revealed that exogeneously added defensin molecules enter the cells, are distributed throughout the cytoplasm and could be detected in cell nuclei. The model study using A549 cells treated with 1,25-(OH)2D3 has shown similar cell growth suppression effect of native endogenously produced hBD-2. Conclusion: The results of our study suggest that in malignant epithelial cells hBD-2 may control cell growth via arrest of G1/S transition and activation of pRB.
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| first_indexed | 2025-11-24T23:49:18Z |
| format | Article |
| fulltext | |
| id | nasplib_isofts_kiev_ua-123456789-138664 |
| institution | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| issn | 1812-9269 |
| language | English |
| last_indexed | 2025-11-24T23:49:18Z |
| publishDate | 2011 |
| publisher | Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| record_format | dspace |
| spelling | Zhuravel, E. Shestakova, T. Efanova, O. Yusefovich, Yu. Kytvin, D. Soldatkina, M. Pogrebnoy, P. 2018-06-19T11:14:50Z 2018-06-19T11:14:50Z 2011 Human beta-defensin-2 controlS cell cycle in malignant epithelial cells: in vitro study / E. Zhuravel, T. Shestakova, O. Efanova, Yu. Yusefovich, D. Lytvin, M. Soldatkina, P. Pogrebnoy // Experimental Oncology. — 2011. — Т. 33, № 3. — С. 114-120. — Бібліогр.: 29 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/138664 Aim: In the present research we analyze the mechanism of human beta-defensin-2 (hBD-2) influence on cultured malignant epithelial cell growth. Materials and Methods: The analysis of a concentration-dependent effect of recombinant hBD-2 (rec-hBD-2) on cell growth patterns and cell cycle distribution has been performed in vitro with 2 cell lines (human lung adenocarcinoma A549 cells and human epidermoid carcinoma A431 cells) using MTT test, flow cytometry and direct cell counting. To study intracellular localization of hBD-2 immunocytofluorescent and immunocytochemical analyses were applied, and effect of hBD-2 on signal cascades involved in cell cycle regulation has been studied by Western blotting. Results: According to our data, rec-hBD-2 exerts a concentration-dependent effect on the viability of cultured A549 and A431 cells. It causes proproliferative effect at concentrations below 1 nM, significant suppression of cell proliferation at concentration range from 10 nM to 1 µM (p<0.05), and cell death at higher concentrations. Using flow cytometry we have demonstrated that hBD-2 dependent growth suppression is realized via cell cycle arrest at G1/S phase (p<0.05). Also, we have registered significant activation of pRB and decreased expression of Cyclin D1 in cells treated with the defensin compared to untreated control cells, while the expression of p53 remains unaffected. The study of intracellular localization of hBD-2 in these cells has revealed that exogeneously added defensin molecules enter the cells, are distributed throughout the cytoplasm and could be detected in cell nuclei. The model study using A549 cells treated with 1,25-(OH)2D3 has shown similar cell growth suppression effect of native endogenously produced hBD-2. Conclusion: The results of our study suggest that in malignant epithelial cells hBD-2 may control cell growth via arrest of G1/S transition and activation of pRB. We express our sincere gratitude to Dr. N.N. Khranovskaya and Dr.O.V. Skachkova (National Cancer Institute, Kyiv, Ukraine) for qualified help in flow cytometry analysis, Dr.V.M. Pushkarev (V.P.Komissarenko Institute of Endocrinology and Metabolism, Kyiv, Ukraine) for expertized guidance in analysis of cell cycle regulation, Dr. V. Kashuba (Karolinska Institute, Sweden) for kindly provided A549 cells, and Dr.L.Apukhovska,Palladin Institute of Biochemistry, Kyiv, Ukraine for kindly provided metabolites of vitamin D3. en Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України Experimental Oncology Original contributions Human beta-defensin-2 controlS cell cycle in malignant epithelial cells: in vitro study Article published earlier |
| spellingShingle | Human beta-defensin-2 controlS cell cycle in malignant epithelial cells: in vitro study Zhuravel, E. Shestakova, T. Efanova, O. Yusefovich, Yu. Kytvin, D. Soldatkina, M. Pogrebnoy, P. Original contributions |
| title | Human beta-defensin-2 controlS cell cycle in malignant epithelial cells: in vitro study |
| title_full | Human beta-defensin-2 controlS cell cycle in malignant epithelial cells: in vitro study |
| title_fullStr | Human beta-defensin-2 controlS cell cycle in malignant epithelial cells: in vitro study |
| title_full_unstemmed | Human beta-defensin-2 controlS cell cycle in malignant epithelial cells: in vitro study |
| title_short | Human beta-defensin-2 controlS cell cycle in malignant epithelial cells: in vitro study |
| title_sort | human beta-defensin-2 controls cell cycle in malignant epithelial cells: in vitro study |
| topic | Original contributions |
| topic_facet | Original contributions |
| url | https://nasplib.isofts.kiev.ua/handle/123456789/138664 |
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