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 J. Pirruccello, Patrick L. Iversen, John D. Jackson, M. Anne Kessinger, J. Graham Sharp

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11 Scopus citations

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

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Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Joshi, S. S., Wu, A. G., Verbik, D. J., Algarra, S. M., Bishop, M. R., Pirruccello, S. J., Iversen, P. L., Jackson, J. D., Kessinger, M. A., & Sharp, J. G. (1996). Oligonucleotides complementary to c-myb messenger RNA inhibit growth and induce apoptosis in human Burkitt lymphoma cells. International journal of oncology, 8(4), 815-820.