Oligonucleotides complementary to c-myb messenger RNA inhibit growth and induce apoptosis in human Burkitt lymphoma cells

A 24-mer (antisense) phosphorothioate oligonucleotide (ODN) corresponding to the codons 2-9 of the c-myb gene was evaluated for its effects on the growth of a human Burkitt lymphoma cell line (Raji) in vitro. Raji cells incubated with different concentrations of c-myb antisense ODN (5-15 M-g/ml) for...

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Autores: Joshi, S.S. (Shantaram S.)|||/items/585ea42f-51c4-4488-8ed4-13e9a0f5adea, Wu, AI.G. (AI G.)|||/items/e7c13550-8fb3-4464-9ef9-50d8534c266b, Verbik, D.J. (David J.)|||/items/e91ddc84-74a0-48c4-96a4-e0a973041baa, Martin-Algarra, S. (Salvador)|||/items/2fba8e8b-e087-4ab0-82e3-a4d157f1e0cc, Bishop, M.R. (Michael R.)|||/items/e3a08487-8583-406c-b9c9-c974f883f7e2, Pirruccello, S.J. (Samuel J.)|||/items/71e413df-5b6f-4c23-b232-7fbf5781e3d8, Iversen, P. L. (Patrick L.)|||/items/728d217d-c98a-4500-8f8e-7d970e177b0e, Jackson, J.D. (John D.)|||/items/e606fbfc-f4f6-4de3-9cd1-995e5cfe53b6, Kessinger, A. (Anne)|||/items/acbc9f8a-7b0c-4143-bc1d-b9677d504681, Graham-Sharp, J. (J.)|||/items/fed833a2-8a01-449c-b2c6-6c2653721d81
Tipo de recurso: artículo
Fecha de publicación:1996
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/68915
Acceso en línea:https://hdl.handle.net/10171/68915
Access Level:acceso abierto
Palabra clave:Burkitt lymphoma
Raji cells
c-myb
Antisense oligonucleotides
Apoptosis
Descripción
Sumario:A 24-mer (antisense) phosphorothioate oligonucleotide (ODN) corresponding to the codons 2-9 of the c-myb gene was evaluated for its effects on the growth of a human Burkitt lymphoma cell line (Raji) in vitro. Raji cells incubated with different concentrations of c-myb antisense ODN (5-15 M-g/ml) for 24-72 h showed a significant dosedependent decrease in growth. The same concentrations of control (sense) or scrambled c-myb phosphorothioate ODNs did not inhibit Raji cell growth. The c-myb antisense ODN, but not the control ODNs, significantly decreased c-myb mRNA levels in treated cells as determined by RT-PCR. Additionally, the c-myb antisense ODN induced apoptosis of Raji cells as demonstrated by i) flow cytometry to enumerate the A0 (apoptotic cell population) population of propidium iodide stained cells; ii) electron microscopy to evaluate the cell morphology; and iii) DNA fragmentation pattern. Thus, an antisense c-myb ODN causes significant growth inhibition of Burkitt lymphoma cells, and one mechanism of growth inhibition is the induction of apoptosis of the lymphoma cells. In addition, antisense c-myb ODN did not reduce CFUGM or BFU-e colony-forming ability of normal hematopoietic stem/progenitor cells. Because the inhibition is sequence-specific and Burkitt lymphoma cell selective, evaluation of the therapeutic effects of c-myb antisense ODN against Burkitt lymphoma is warranted.