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 Citations (Scopus)

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
StatePublished - Nov 15 2002
Externally publishedYes

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Antimony Sodium Gluconate
Protein Tyrosine Phosphatases
Neoplasms
Phosphoric Monoester Hydrolases
Tyrosine
Phosphorylation
Cell Line
Nude Mice
Chromatography
Melanoma

ASJC Scopus subject areas

  • Immunology

Cite this

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.

Anticancer activity of sodium stibogluconate in synergy with IFNs. / Yi, Taolin; Pathak, Manas K.; Lindner, Daniel J.; Ketterer, Michael E; Farver, Carol; Borden, Ernest C.

In: Journal of Immunology, Vol. 169, No. 10, 15.11.2002, p. 5978-5985.

Research output: Contribution to journalArticle

Yi, T, Pathak, MK, Lindner, DJ, Ketterer, ME, Farver, C & Borden, EC 2002, 'Anticancer activity of sodium stibogluconate in synergy with IFNs', Journal of Immunology, vol. 169, no. 10, pp. 5978-5985.
Yi T, Pathak MK, Lindner DJ, Ketterer ME, Farver C, Borden EC. Anticancer activity of sodium stibogluconate in synergy with IFNs. Journal of Immunology. 2002 Nov 15;169(10):5978-5985.
Yi, Taolin ; Pathak, Manas K. ; Lindner, Daniel J. ; Ketterer, Michael E ; Farver, Carol ; Borden, Ernest C. / Anticancer activity of sodium stibogluconate in synergy with IFNs. In: Journal of Immunology. 2002 ; Vol. 169, No. 10. pp. 5978-5985.
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