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Cytomodulation of interleukin-2 effect by l-2-oxothiazolidine-4-carboxylate on human malignant melanoma

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Abstract

Glutathione (GSH), the most prevalent intracellular non-protein thiol, plays an important role in the interleukin-2 (IL-2)-induced proliferative activity of normal and tumour cells expressing IL-2 receptor (IL-2R). In the present study, we investigate the effect of IL-2 on proliferation of the human melanoma A375 cell line, and the possible selective cytomodulation effect of this cytokine by l-2-oxothiazolidine-4-carboxylate (OTZ) on these melanoma cells and on human peripheral blood mononuclear cells (PBMCs). We found that recombinant IL-2 (rIL-2) significantly increased the proliferation rate of A375 melanoma cells, which was associated with an increase in GSH levels, the enhancement of IL-2Rα expression and the endogenous production of IL-2 in these tumour cells. In contrast, OTZ decreased GSH content and the proliferation rate of A375 cells, and abrogated the growth-promoting effects of rIL-2. Thus, compared to cells treated with rIL-2, pre-treatment with OTZ reduced IL-2Rα expression, and also decreased the consumption of rIL-2 and the endogenous secretion of IL-2 by these tumour cells. With regard to PBMCs, the combination of OTZ plus rIL-2 resulted in a more rapid and greater increase of IL-2Rα expression than rIL-2 alone, with the proliferation rate being similar in the first 24 h, but with a lower PBMC′ count found thereafter compared to rIL-2 treatment alone. These results suggest that OTZ plays a crucial role in obtaining a selective cytomodulation of rIL-2, enabling it to exert its growth-promoting effect on normal cells, but not on melanoma cells, thereby possibly improving biochemotherapy with rIL-2.

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Acknowledgements

We are grateful to A. Iglesias for assistance with flow cytometry. This work was supported by the University of the Basque Country (project 9/U.P.V. 00077.327-15830/2004), F.I.S (PI030452) and the Jesús Gangoiti Barrera Foundation.

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Authors and Affiliations

  1. Department of Surgery, Radiology and Physical Medicine, School of Medicine and Dentistry, University of the Basque Country, Leioa, 48940, Vizcaya, Spain

    Pedro Bilbao & Teodoro Palomares

  2. Department of Cell Biology and Histology, School of Medicine and Dentistry, University of the Basque Country, Leioa, 48940, Vizcaya, Spain

    Maite del Olmo, Ana Alonso-Varona & Begoña Castro

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  1. Maite del Olmo
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  2. Ana Alonso-Varona
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Correspondence to Teodoro Palomares.

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Olmo, M.d., Alonso-Varona, A., Castro, B. et al. Cytomodulation of interleukin-2 effect by l-2-oxothiazolidine-4-carboxylate on human malignant melanoma. Cancer Immunol Immunother 55, 948–957 (2006). https://doi.org/10.1007/s00262-005-0087-5

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