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

Shantaram S Joshi, Ai G. Wu, David J. Verbik, S. M. Algarra, Michael R. Bishop, Samuel Jay Pirruccello, Patrick L. Iversen, John D. Jackson, M. Anne Kessinger, John G Sharp

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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 μg/ml) for 24-72 h showed a significant dose-dependent 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 CFU-GM 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.

Original languageEnglish (US)
Pages (from-to)815-820
Number of pages6
JournalInternational journal of oncology
Volume8
Issue number4
StatePublished - Apr 1 1996

Fingerprint

Burkitt Lymphoma
Oligonucleotides
Apoptosis
Messenger RNA
Growth
Hematopoietic Stem Cells
myb Genes
Phosphorothioate Oligonucleotides
Granulocyte-Macrophage Progenitor Cells
Propidium
Antisense Oligonucleotides
Therapeutic Uses
DNA Fragmentation
Codon
Population
Lymphoma
Electron Microscopy
Flow Cytometry
Cell Line
Polymerase Chain Reaction

Keywords

  • Antisense oligonucleotides
  • Apoptosis
  • Burkitt lymphoma
  • Raji cells
  • c-myb

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Oligonucleotides complementary to c-myb messenger RNA inhibit growth and induce apoptosis in human Burkitt lymphoma cells. / Joshi, Shantaram S; Wu, Ai G.; Verbik, David J.; Algarra, S. M.; Bishop, Michael R.; Pirruccello, Samuel Jay; Iversen, Patrick L.; Jackson, John D.; Kessinger, M. Anne; Sharp, John G.

In: International journal of oncology, Vol. 8, No. 4, 01.04.1996, p. 815-820.

Research output: Contribution to journalArticle

Joshi, Shantaram S ; Wu, Ai G. ; Verbik, David J. ; Algarra, S. M. ; Bishop, Michael R. ; Pirruccello, Samuel Jay ; Iversen, Patrick L. ; Jackson, John D. ; Kessinger, M. Anne ; Sharp, John G. / Oligonucleotides complementary to c-myb messenger RNA inhibit growth and induce apoptosis in human Burkitt lymphoma cells. In: International journal of oncology. 1996 ; Vol. 8, No. 4. pp. 815-820.
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AU - Wu, Ai G.

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AU - Algarra, S. M.

AU - Bishop, Michael R.

AU - Pirruccello, Samuel Jay

AU - Iversen, Patrick L.

AU - Jackson, John D.

AU - Kessinger, M. Anne

AU - Sharp, John G

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