Open Access

Induction of arginosuccinate synthetase (ASS) expression affects the antiproliferative activity of arginine deiminase (ADI) in melanoma cells

  • Authors:
    • Antonella Manca
    • Maria Cristina Sini
    • Francesco Izzo
    • Paolo A. Ascierto
    • Fabiana Tatangelo
    • Gerardo Botti
    • Giusy Gentilcore
    • Marilena Capone
    • Nicola Mozzillo
    • Carla Rozzo
    • Antonio Cossu
    • Francesco Tanda
    • Giuseppe Palmieri
  • View Affiliations

  • Published online on: March 18, 2011     https://doi.org/10.3892/or.2011.1220
  • Pages: 1495-1502
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Abstract

Arginine deiminase (ADI), an arginine-degrading enzyme, has been used in the treatment of tumours sensitive to arginine deprivation, such as malignant melanoma (MM) and hepatocellular carcinoma (HCC). Endogenous production of arginine is mainly dependent on activity of ornithine transcarbamylase (OTC) and argininosuccinate synthetase (ASS) enzymes. We evaluated the effect of ADI treatment on OTC and ASS expression in a series of melanoma cell lines. Twenty-five primary melanoma cell lines and normal fibroblasts as controls underwent cell proliferation assays and Western blot analyses in the presence or absence of ADI. Tissue sections from primary MMs (N=20) and HCCs (N=20) were investigated by immunohistochemistry for ASS expression. Overall, 21/25 (84%) MM cell lines presented a cell growth inhibition by ADI treatment; none of them presented constitutive detectable levels of the ASS protein. However, 7/21 (33%) ADI-sensitive melanoma cell lines presented markedly increased expression levels of the ASS protein following ADI treatment, with a significantly higher IC50 median value. Growth was not inhibited and the IC50 was not reached among the remaining 4/25 (16%) MM cell lines; all of them showed constitutive ASS expression. The OTC protein was found expressed in all melanoma cell lines before and after the ADI treatment. Lack of ASS immunostaining was observed in all analyzed in vivo specimens. Our findings suggest that response to ADI treatment in melanoma is significantly correlated with the ability of cells to express ASS either constitutively at basal level (inducing drug resistance) or after the treatment (reducing sensitivity to ADI).

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June 2011
Volume 25 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Manca A, Sini MC, Izzo F, Ascierto PA, Tatangelo F, Botti G, Gentilcore G, Capone M, Mozzillo N, Rozzo C, Rozzo C, et al: Induction of arginosuccinate synthetase (ASS) expression affects the antiproliferative activity of arginine deiminase (ADI) in melanoma cells. Oncol Rep 25: 1495-1502, 2011
APA
Manca, A., Sini, M.C., Izzo, F., Ascierto, P.A., Tatangelo, F., Botti, G. ... Palmieri, G. (2011). Induction of arginosuccinate synthetase (ASS) expression affects the antiproliferative activity of arginine deiminase (ADI) in melanoma cells. Oncology Reports, 25, 1495-1502. https://doi.org/10.3892/or.2011.1220
MLA
Manca, A., Sini, M. C., Izzo, F., Ascierto, P. A., Tatangelo, F., Botti, G., Gentilcore, G., Capone, M., Mozzillo, N., Rozzo, C., Cossu, A., Tanda, F., Palmieri, G."Induction of arginosuccinate synthetase (ASS) expression affects the antiproliferative activity of arginine deiminase (ADI) in melanoma cells". Oncology Reports 25.6 (2011): 1495-1502.
Chicago
Manca, A., Sini, M. C., Izzo, F., Ascierto, P. A., Tatangelo, F., Botti, G., Gentilcore, G., Capone, M., Mozzillo, N., Rozzo, C., Cossu, A., Tanda, F., Palmieri, G."Induction of arginosuccinate synthetase (ASS) expression affects the antiproliferative activity of arginine deiminase (ADI) in melanoma cells". Oncology Reports 25, no. 6 (2011): 1495-1502. https://doi.org/10.3892/or.2011.1220