Alterations of c-myc Expression by Antisense Oligodeoxynucleotides Enhance the Induction of Apoptosis in HL-60 Cells

Shinya Kimura, Kouichi Hirakawa, Taira Maekawa, Tatsuo Abe, Akira Murakami

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    Abstract

    This study was designed using c-myc antisense oligodeoxynucleoside phosphorothioate (AS PS-ODN) to evaluate how alterations of c-myc expression in HL-60 human myeloid leukemia cells could influence the induction of apoptosis. Unexpectedly both the continuous down-regulation of c-myc expression caused by exposure to c-myc AS PS-ODN and up-regulation after its withdrawal influenced apoptosis. We found that continuous suppression of c-myc expression by 10 um c-myc AS PS-ODN could decrease the proliferation of HL-60 cells to approximately 60% of the control growth after 3 days of suspension culture, and when assessed morphologically the percentage of cells undergoing apoptosis was 3.5%. Evidence either of cell cycle arrest or cell cycle prolongation was not detected. It is likely that apoptosis induced by the sustained down-regulation of c-myc expression with AS PS-ODN treatment was solely sufficient to explain the inhibition of cell proliferation. Up-regulation of c-myc expression was observed within 1 h after c-myc AS PS-ODN withdrawal. This up-regulation further enhanced induction of apoptosis and involved up to 32% of the cells. These results suggest that while the continuous suppression of c-myc expression caused a constant effect on the induction of apoptosis, its abrupt up-regulation could rapidly drive a considerable number of HL-60 cells into the apoptotic pathway.

    Original languageEnglish (US)
    Pages (from-to)1379-1384
    Number of pages6
    JournalCancer research
    Volume55
    Issue number6
    StatePublished - Mar 15 1995

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    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

    Cite this

    Kimura, S., Hirakawa, K., Maekawa, T., Abe, T., & Murakami, A. (1995). Alterations of c-myc Expression by Antisense Oligodeoxynucleotides Enhance the Induction of Apoptosis in HL-60 Cells. Cancer research, 55(6), 1379-1384.