The Effects of Forodesine in Murine and Human Multiple Myeloma Cells
Multiple myeloma (MM) is the second most commonly diagnosed hematological malignancy, characterized by a monoclonal proliferation of malignant cells in the bone marrow. Despite recent advances in treatment strategies, MM remains incurable and new therapeutical targets are needed. Recently forodesine...
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| Format: | Article |
| Language: | English |
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Wiley
2010-01-01
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| Series: | Advances in Hematology |
| Online Access: | http://dx.doi.org/10.1155/2010/131895 |
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| author | Liesbeth Bieghs Jo Caers Elke De Bruyne Els Van Valckenborgh Fiona Higginbotham Karin Vanderkerken Eline Menu |
| author_facet | Liesbeth Bieghs Jo Caers Elke De Bruyne Els Van Valckenborgh Fiona Higginbotham Karin Vanderkerken Eline Menu |
| author_sort | Liesbeth Bieghs |
| collection | DOAJ |
| description | Multiple myeloma (MM) is the second most commonly diagnosed hematological malignancy, characterized by a monoclonal proliferation of malignant cells in the bone marrow. Despite recent advances in treatment strategies, MM remains incurable and new therapeutical targets are needed. Recently forodesine, a purine nucleoside phosphorylase inhibitor, was found to induce apoptosis in leukemic cells of chronic lymphocytic leukemia patients by increasing the dGTP levels. We therefore tested whether forodesine was able to inhibit proliferation and/or induce apoptosis in both murine and human MM cells through a similar pathway. We found that after 48 hours of treatment with forodesine there was a slight dGTP increase in 5T33MM and RPMI-8226 MM cells associated with partial inhibition of proliferation and a limited induction of apoptosis. When investigating the pathways leading to cell cycle arrest and apoptosis, we observed an upregulation of p27, caspase 3, and BIM. We can conclude that forodesine has some effects on MM cells but not as impressive as the known effects in leukemic cells. Forodesine might be however potentiating towards other established cytotoxic drugs in MM. |
| format | Article |
| id | doaj-art-adb7fbce79014dada2119e3e212e9da5 |
| institution | Kabale University |
| issn | 1687-9104 1687-9112 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advances in Hematology |
| spelling | doaj-art-adb7fbce79014dada2119e3e212e9da52025-02-03T01:26:52ZengWileyAdvances in Hematology1687-91041687-91122010-01-01201010.1155/2010/131895131895The Effects of Forodesine in Murine and Human Multiple Myeloma CellsLiesbeth Bieghs0Jo Caers1Elke De Bruyne2Els Van Valckenborgh3Fiona Higginbotham4Karin Vanderkerken5Eline Menu6Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, BelgiumLe Departement d'Hématologie Clinique, Centre Hospitalier Universitaire de Liège, 4000 Liège, BelgiumDepartment of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, BelgiumDepartment of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, BelgiumMundipharma International Limited, Milton Road, Cambridge CB4 0GW, UKDepartment of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, BelgiumDepartment of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, BelgiumMultiple myeloma (MM) is the second most commonly diagnosed hematological malignancy, characterized by a monoclonal proliferation of malignant cells in the bone marrow. Despite recent advances in treatment strategies, MM remains incurable and new therapeutical targets are needed. Recently forodesine, a purine nucleoside phosphorylase inhibitor, was found to induce apoptosis in leukemic cells of chronic lymphocytic leukemia patients by increasing the dGTP levels. We therefore tested whether forodesine was able to inhibit proliferation and/or induce apoptosis in both murine and human MM cells through a similar pathway. We found that after 48 hours of treatment with forodesine there was a slight dGTP increase in 5T33MM and RPMI-8226 MM cells associated with partial inhibition of proliferation and a limited induction of apoptosis. When investigating the pathways leading to cell cycle arrest and apoptosis, we observed an upregulation of p27, caspase 3, and BIM. We can conclude that forodesine has some effects on MM cells but not as impressive as the known effects in leukemic cells. Forodesine might be however potentiating towards other established cytotoxic drugs in MM.http://dx.doi.org/10.1155/2010/131895 |
| spellingShingle | Liesbeth Bieghs Jo Caers Elke De Bruyne Els Van Valckenborgh Fiona Higginbotham Karin Vanderkerken Eline Menu The Effects of Forodesine in Murine and Human Multiple Myeloma Cells Advances in Hematology |
| title | The Effects of Forodesine in Murine and Human Multiple Myeloma Cells |
| title_full | The Effects of Forodesine in Murine and Human Multiple Myeloma Cells |
| title_fullStr | The Effects of Forodesine in Murine and Human Multiple Myeloma Cells |
| title_full_unstemmed | The Effects of Forodesine in Murine and Human Multiple Myeloma Cells |
| title_short | The Effects of Forodesine in Murine and Human Multiple Myeloma Cells |
| title_sort | effects of forodesine in murine and human multiple myeloma cells |
| url | http://dx.doi.org/10.1155/2010/131895 |
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