In vitro and in vivo activity of 4-thio-uridylate against JY cells, a model for human acute lymphoid leukemia
- Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary)
- Department of Pharmacology and Pharmacotherapy, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary)
- Cell Biology and Signaling Research Group of the Hungarian Academy of Sciences, Department of Biophysics and Cell Biology, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary)
- 3rd Department of Internal Medicine, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary)
- Department of Pediatrics, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary)
- Coordinating Department of Surgical Techniques, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary)
- Department of Dermatology, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032 (Hungary)
Highlights: {yields} s{sup 4}UMP a naturally occurring thiolated nucleotide, effectively inhibited the proliferation of JY cells in vitro and in vivo. {yields} s{sup 4}UMP decreased the cell number and colony forming activity of leukemia cells in SCID mice. {yields} The effect of s{sup 4}UMP was undetectable on the bone marrow of healthy mice. {yields} The biochemical changes of the treated cells suggested that s{sup 4}UMP induced apoptosis. -- Abstract: We have previously reported the in vitro anti-proliferative effect of 4-thio-uridylate (s{sup 4}UMP) on OCM-1 uveal melanoma cells. Here, we assessed the efficacy of s{sup 4}UMP on JY cells. Treatment of JY cells with s{sup 4}UMP suppressed their colony forming activity and induced apoptosis; healthy human bone marrow granulocyte-macrophage progenitor cells were 14-fold less sensitive to the nucleotide. In vivo effectiveness of s{sup 4}UMP was determined using xenograft SCID mouse model. s{sup 4}UMP decreased the cell number and colony forming activity of the total cell content of the femur of SCID mice transplanted with JY cells without affecting the bone marrow of healthy mice. These results suggest that s{sup 4}UMP alone or in combination with other clinically approved anti-leukemic remedies should be further explored as a potential novel therapeutic agent.
- OSTI ID:
- 22204995
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 410, Issue 3; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Hemopoietic stem-cell compartment of the SCID mouse: Double-exponential survival curve after [gamma] irradiation
The orphan nuclear receptor EAR-2 (NR2F6) inhibits hematopoietic cell differentiation and induces myeloid dysplasia in vivo