Anticancer activity of sodium stibogluconate in synergy with IFNs

Taolin Yi, Manas K. Pathak, Daniel J. Lindner, Michael E. Ketterer, Carol Farver, Ernest C. Borden

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Cancer cell resistance limits the efficacy of IFNs. In this study, we show that sodium stibogluconate (SSG) and IFN-α synergized to overcome IFN-α resistance in various human cancer cell lines in culture and eradicated IFN-α-refractory WM9 human melanoma tumors in nude mice with no obvious toxicity. SSG enhanced IFN-α-induced Stat1 tyrosine phosphorylation, inactivated intracellular SHP-1 and SHP-2 that negatively regulate IFN signaling, and induced cellular protein tyrosine phosphorylation in cancer cell lines. These effects are consistent with inactivation of phosphatases as the basis of SSG anticancer activity. Characterization of SSG by chromatography revealed that only selective compounds in SSG were effective protein tyrosine phosphatase inhibitors. These observations suggest the potential of SSG as a clinically usable protein tyrosine phosphatase inhibitor in cancer treatment and provide insights for developing phosphatase-targeted therapeutics.

Original languageEnglish (US)
Pages (from-to)5978-5985
Number of pages8
JournalJournal of Immunology
Volume169
Issue number10
DOIs
StatePublished - Nov 15 2002
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Yi, T., Pathak, M. K., Lindner, D. J., Ketterer, M. E., Farver, C., & Borden, E. C. (2002). Anticancer activity of sodium stibogluconate in synergy with IFNs. Journal of Immunology, 169(10), 5978-5985. https://doi.org/10.4049/jimmunol.169.10.5978