HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yi, T. Articles by Borden, E. C. Search for Related Content PubMed PubMed Citation Articles by Yi, T. Articles by Borden, E. C.

Anticancer Activity of Sodium Stibogluconate in Synergy with IFNs¹

Taolin Yi^2,*,, Manas K. Pathak^*, Daniel J. Lindner, Michael E. Ketterer, Carol Farver and Ernest C. Borden^*,

^* Department of Cancer Biology, Lerner Research Institute, Taussig Cancer Center, and Department of Pathology, Cleveland Clinic Foundation, Cleveland, OH 44195; and Department of Chemistry, Northern Arizona University Flagstaff, AZ 86011

Cancer cell resistance limits the efficacy of IFNs. In this study, we show that sodium stibogluconate (SSG) and IFN- synergized to overcome IFN- resistance in various human cancer cell lines in culture and eradicated IFN--refractory WM9 human melanoma tumors in nude mice with no obvious toxicity. SSG enhanced IFN--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.

This article has been cited by other articles:

				K. El Fadili, M. Imbeault, N. Messier, G. Roy, B. Gourbal, M. Bergeron, M. J. Tremblay, D. Legare, and M. Ouellette Modulation of Gene Expression in Human Macrophages Treated with the Anti-Leishmania Pentavalent Antimonial Drug Sodium Stibogluconate Antimicrob. Agents Chemother., February 1, 2008; 52(2): 526 - 533. [Abstract] [Full Text] [PDF]

				J. Mookerjee Basu, A. Mookerjee, P. Sen, S. Bhaumik, P. Sen, S. Banerjee, K. Naskar, S. K. Choudhuri, B. Saha, S. Raha, et al. Sodium Antimony Gluconate Induces Generation of Reactive Oxygen Species and Nitric Oxide via Phosphoinositide 3-Kinase and Mitogen-Activated Protein Kinase Activation in Leishmania donovani-Infected Macrophages. Antimicrob. Agents Chemother., May 1, 2006; 50(5): 1788 - 1797. [Abstract] [Full Text] [PDF]

				K. Fan, M. Zhou, M. K. Pathak, D. J. Lindner, C. Z. Altuntas, V. K. Tuohy, E. C. Borden, and T. Yi Sodium Stibogluconate Interacts with IL-2 in Anti-Renca Tumor Action via a T Cell-Dependent Mechanism in Connection with Induction of Tumor-Infiltrating Macrophages J. Immunol., November 15, 2005; 175(10): 7003 - 7008. [Abstract] [Full Text] [PDF]

				D.-R. Hwang, R.-K. Lin, G.-Z. Leu, T.-Y. Lin, T.-W. Lien, M.-C. Yu, C.-T. Yeh, and J. T.-A. Hsu Inhibition of Hepatitis C Virus Replication by Antimonial Compounds Antimicrob. Agents Chemother., October 1, 2005; 49(10): 4197 - 4202. [Abstract] [Full Text] [PDF]

				P. Chen, M. Levis, P. Brown, K.-T. Kim, J. Allebach, and D. Small FLT3/ITD Mutation Signaling Includes Suppression of SHP-1 J. Biol. Chem., February 18, 2005; 280(7): 5361 - 5369. [Abstract] [Full Text] [PDF]

				D. E. Spaner Amplifying cancer vaccine responses by modifying pathogenic gene programs in tumor cells J. Leukoc. Biol., August 1, 2004; 76(2): 338 - 351. [Abstract] [Full Text] [PDF]