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Chronic exposure to agmatine results in the selection of agmatine-resistant hepatoma cells

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An Erratum to this article was published on 22 February 2012

Abstract

During our study of the cytostatic effect of agmatine, we were able to isolate an agmatine resistant clone from a parental hepatoma cell line, HTC. These cells, called Agres, had slower growth rate than the parental cells when cultured in normal medium. The modification in polyamine content induced by agmatine was much lower in these cells and ornithine decarboxylase, S-adenosylmethionine decarboxylase and spermidine/spermine acetyltransferase activities were much less affected. By investigating the mechanism responsible for these modifications, it was shown that agmatine and polyamines were not taken up by Agres cells. Their resistance to the antiproliferative effects of agmatine may thus arise from a lack of the polyamine transport system. Moreover, Agres cells were able to take up both glutamic acid and arginine at a rate significantly higher than that detected for HTC cells, most likely to provide components for compensatory increase of PA synthesis. These results emphasize the importance of polyamine transport for cell growth.

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Abbreviations

DFMO:

Difluoromethylornithine

MGBG:

Methylglyoxal bisguanylhydrazone

ODC:

Ornithine decarboxylase

PUT:

Putrescine

SAMDC:

S-adenosylmethionine decarboxylase

SPD:

Spermidine

SPM:

Spermine

SSAT:

Spermidine/spermine acetyltransferase

HTC:

Rat hepatoma cells

PA:

Polyamines

ECL:

Enhanced chemiluminescence

Agres:

Agmatine resistant cell line

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Acknowledgments

This work was partially supported by Istituto Superiore di Sanità “Project Italy-USA”, by Istituto Pasteur–Fondazione Cenci Bolognetti, by funds MIUR-PRIN (Cofin) and by Fondazione Bossolasco (Torino).

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Authors and Affiliations

  1. Department of Experimental Medicine and Oncology, University of Torino, via Michelangelo 27B, 10126, Turin, Italy

    Bandino Andrea, Bravoco Vittoria, Busletta Chiara, Compagnone Alessandra, Cravanzola Carlo, Meli Floriana, Parola Maurizio & Colombatto Sebastiano

  2. Department of Biological Chemistry, University of Padua, Viale G. Colombo 3, 35121, Padua, Italy

    Battaglia Valentina

  3. Department of Biochemical Sciences, Institute Biology and Molecular Pathology, Istituto Pasteur–Fondazione Cenci Bolognetti, SAPIENZA University of Rome and CNR, Piazzale Aldo Moro 5, 00185, Rome, Italy

    Agostinelli Enzo

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  1. Bandino Andrea
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Correspondence to Colombatto Sebastiano.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00726-012-1241-y.

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Andrea, B., Valentina, B., Vittoria, B. et al. Chronic exposure to agmatine results in the selection of agmatine-resistant hepatoma cells. Amino Acids 42, 769–774 (2012). https://doi.org/10.1007/s00726-011-0993-0

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  • DOI: https://doi.org/10.1007/s00726-011-0993-0

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