The effect of 3-aminobenzamide, inhibitor of poly(ADP-ribose) polymerase, on human osteosarcoma cells

  • Authors:
    • Anna De Blasio
    • Maria T. Musmeci
    • Michela Giuliano
    • Marianna Lauricella
    • Sonia Emanuele
    • Antonella D'Anneo
    • Barbara Vassallo
    • Giovanni Tesoriere
    • Renza Vento
  • View Affiliations

  • Published online on: December 1, 2003     https://doi.org/10.3892/ijo.23.6.1521
  • Pages: 1521-1528
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Abstract

This study demonstrates that in human osteosarcoma cells treatment with 3-aminobenzamide (3-AB), a potent inhibitor of poly(ADP-ribose) polymerase (PARP), induces morphological and biochemical features of differentiation, the duration of which depends on whether or not the normal RB gene is expressed. In Saos-2 cells expressing a non-functional Rb protein, 3-AB treatment induced the formation of transient, short dendritic-like protrusions. In RB-transfected-Saos-2 cells (a clone previously generated in our laboratory that shows stable expression of wild-type Rb protein), 3-AB induced marked and prolonged changes with the formation of long dendritic-like protrusions and the appearance of stellate (osteocyte-like) cells. In MG-63 cells producing a wild-type Rb protein, 3-AB treatment had more marked effects, with a larger number of cells assuming the stellate appearance of osteocytes, which were connected to each other via junctions resembling small channels. Regardless of cell type, at some point after 3-AB treatment the differentiative attempt failed and the cells died. Death was apoptotic, as demonstrated by chromatin condensation and fragmentation, specific cleavage of PARP and Lamin-B, processing of caspase-3 and the appearance of Bax immunoreactive species. Enzymatic assay and RT-PCR of alkaline phosphatase (ALP) - an enzyme whose levels markedly decrease when osteoblasts undergo terminal differentiation into osteocytes - showed that 3-AB treatment markedly lowered ALP expression. Simultaneously, 3-AB treatment markedly increased the expression of CD44, a transmembrane multifunctional adhesion molecule and sensitive marker of osteocytic differentiation. This study hypothesizes a cross-talk between pRb and PARP and suggests that PARP may be a useful target for anticancer drugs.

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December 2003
Volume 23 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
De Blasio A, Musmeci MT, Giuliano M, Lauricella M, Emanuele S, D'Anneo A, Vassallo B, Tesoriere G and Vento R: The effect of 3-aminobenzamide, inhibitor of poly(ADP-ribose) polymerase, on human osteosarcoma cells. Int J Oncol 23: 1521-1528, 2003.
APA
De Blasio, A., Musmeci, M.T., Giuliano, M., Lauricella, M., Emanuele, S., D'Anneo, A. ... Vento, R. (2003). The effect of 3-aminobenzamide, inhibitor of poly(ADP-ribose) polymerase, on human osteosarcoma cells. International Journal of Oncology, 23, 1521-1528. https://doi.org/10.3892/ijo.23.6.1521
MLA
De Blasio, A., Musmeci, M. T., Giuliano, M., Lauricella, M., Emanuele, S., D'Anneo, A., Vassallo, B., Tesoriere, G., Vento, R."The effect of 3-aminobenzamide, inhibitor of poly(ADP-ribose) polymerase, on human osteosarcoma cells". International Journal of Oncology 23.6 (2003): 1521-1528.
Chicago
De Blasio, A., Musmeci, M. T., Giuliano, M., Lauricella, M., Emanuele, S., D'Anneo, A., Vassallo, B., Tesoriere, G., Vento, R."The effect of 3-aminobenzamide, inhibitor of poly(ADP-ribose) polymerase, on human osteosarcoma cells". International Journal of Oncology 23, no. 6 (2003): 1521-1528. https://doi.org/10.3892/ijo.23.6.1521