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The Hidden Side of Disodium Cromolyn: from Mast Cell Stabilizer to an Angiogenic Factor and Antitumor Agent

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Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Scattered data suggested that disodium cromolyn, well known as a mast cell stabilizer shows some effects on tumor cells and tumor-associated newly formed vascular networks. Most of these studies used tumor cell lines assessed by in vitro studies. Nor disodium cromolyn effects on melanoma cell lines were studied yet, neither its influence on recruited tumor blood vessels or angiogenic growth factors expression. We designed here a study regarding disodium cromolyn effects on A375 melanoma tumor cells implanted on chick embryo chorioallantoic membrane (CAM) and on blood vessels recruited by the experimental melanoma in the absence of mast cells, knowing that within CAM, the existence of mast cells are not certified yet. We also assessed the role of disodium cromolyn on the expression of several angiogenic growth factors. Disodium cromoglycate differentially acts on tumor cells and blood vessels. Extensive necrotic areas of experimental melanoma together with an increased number of peritumor blood vessels were observed in treated specimens as compared with untreated tumors. Disodium cromolyn inhibited VEGF and PDGF-BB expression, and had no effects on EG VEGF expression between treated and non treated specimens in a mast cells free microenvironment. Our results sustain the direct antitumor effects of sodium cromolyn and suggest the involvement of several growth factors in the recruitment of tumor vessels by A375 melanoma tumor cells. The expression of growth factors is differentially influenced by sodium cromolyn treatment.

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Acknowledgments

This work was supported in part by internal funds from Victor Babes University of Medicine and Pharmacy Timisoara, Romania. Special thanks to Stefana Avram and to Professor Cristina Adriana Dehelean both from Faculty of Pharmacy of Victor Babes University of Medicine and Pharmacy Timisoara, Romania for valuable technical support in experimental model and for providing us A375 melanoma cells.

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  1. Department of Microscopic Morphology/Histology, Angiogenesis Research Center, “Victor Babes” University of Medicine and Pharmacy, Pta Eftimie Murgu 2, Timisoara, 300041, Romania

    Anca Maria Cimpean & Marius Raica

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  1. Anca Maria Cimpean
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  2. Marius Raica
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Correspondence to Anca Maria Cimpean.

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Cimpean, A.M., Raica, M. The Hidden Side of Disodium Cromolyn: from Mast Cell Stabilizer to an Angiogenic Factor and Antitumor Agent. Arch. Immunol. Ther. Exp. 64, 515–522 (2016). https://doi.org/10.1007/s00005-016-0408-8

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  • DOI: https://doi.org/10.1007/s00005-016-0408-8

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