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Suramin: an anticancer drug with unique biological effects

Conclusion and perspectives

At present the primary mechanism(s) of suramin action is not known. It is possible that several of the factors mentioned in this review are of importance for the drug's antitumor activity and even that different mechanisms are of importance for different cell types. An improved knowledge about the relative importance of the many different biologic effects of suramin is essential to the establishment of better drug combinations and to the development of suramin derivatives with an improved therapeutic index. The development and characterization of suramin-resistant cells would be a major step in this direction.

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References

  1. Betsholtz C, Johnsson A, Heldin CH, Westermark B (1986) Efficient reversion of simian sarcoma virus transformation and inhibition of growth factor-induced mitogenesis by suramin. Proc Natl Acad Sci USA 83:6440

    Google Scholar 

  2. Bojanowski K, Lelievre S, Markovits J, Couprie J, Jacquemin-Sablon A, Larsen AK (1992) Suramin is an inhibitor of DNA topoisomerase II in vitro and in Chinese hamster sarcoma cells. Proc Natl Acad Sci USA 89:3025

    Google Scholar 

  3. Butler SJ, Kelly CH, McKenzie FR, Guild SB, Wakelam MJO, Milligan G (1988) Differential effects of suramin on the coupling of receptors to individual species of pertussis-toxin-sensitive guaninenucleotide-binding proteins. Biochem J 251:201

    Google Scholar 

  4. Calcaterra NB, Vicario LR, Roveri OA (1988) Inhibition by suramin of mitochondrial ATP synthesis. Biochem Pharmacol 37:2521

    Google Scholar 

  5. Cheson BD, Levine AM, Mildvan D, Kaplan LD, Wolfe P, Rios A, Groopman JE, Gill P, Volberding PA, Poiesz BJ, Gottlieb MS, Holden H, Volsky DJ, Silver SS, Hawkins MJ (1987) Suramin therapy in AIDS and related disorders. Report of the US Suramin Working Group. JAMA 258:1347

    Google Scholar 

  6. Coffey RJ, Leof EB, Shipley GD, Moses HL (1987) Suramin inhibition of growth factor receptor binding and mitogenicity in AKR-2B cells. J Cell Physiol 132:143

    Google Scholar 

  7. Constantopoulos G, Rees S, Cragg BG, Barranger JA, Brady RO (1980) Experimental animal model for mucopolysaccharidoses: suramin-induced glycosaminoglycan and sphingolipid accumulation in the rat. Proc Natl Acad Sci USA 77:3700

    Google Scholar 

  8. Constantopoulos G, Rees S, Cragg BG, Barranger JA, Brady RO (1981) Effect of suramin on the activities of degradative enzymes of sphingolipids in rats. Res Commun Chem Pathol Pharmacol 32:87

    Google Scholar 

  9. De Clercq E (1979) Suramin: a potent inhibitor of the reverse transcriptase of RNA tumor viruses. Cancer Lett 8:9

    Google Scholar 

  10. Educational book (1991) Novel targets for cancer therapy, American Society of Clinical Oncology, p 189

  11. Fantini J, Rognoni JB, Roccabianca M, Pommier G, Marvaldi J (1989) Suramin inhibits cell growth and glycolytic activity and triggers differentiation of human colic adrenocarcinoma cell clone HT29-D4. J Biol Chem 264:10282

    Google Scholar 

  12. Fantini J, Guo X-J, Marvaldi J, Rougon G (1990) Suramin inhibits proliferation of rat glioma cells and alters N-CAM cell surface expression. Int J Cancer 45:554

    Google Scholar 

  13. Fortes PAG Ellory JC, Lew VL (1973) Suramin: a potent ATPase inhibitor which acts on the inside surface of the sodium pump. Biochim Biophys Acta 318:262

    Google Scholar 

  14. Hawking F (1978) Suramin: with special reference to onchocerciasis. Adv Pharmacol Chemother 15:289

    Google Scholar 

  15. Hensey CE, Boscoboinik D, Azzi A (1989) Suramin, an anticancer drug, inhibits protein kinase C and induces differentiation in neuroblastoma cell clone NB2A. FEBS Lett 258:156

    Google Scholar 

  16. Hosang M (1985) Suramin binds to platelet-derived growth factor and inhibits its biological activity. J Cell Biochem 29:265

    Google Scholar 

  17. Huang JS, Huang SS, Kuo MD (1986) Bovine brain-derived growth factor. Purification and characterization of its interaction with responsive cells. J Biol Chem 261:11600

    Google Scholar 

  18. Jamis-Dow CA, Weiss GH, Merino MJ, Cooper MR, Lenehan WM, Myers CE (1991) Suramin selectively localizes to vascular endothelial cells: a possible basis for the antiangiogenesis activity of suramin. Proc Am Assoc Cancer Res 32:495

    Google Scholar 

  19. Jindal HK, Anderson CW, Davis RG, Vishwanatha JK (1990) Suramin affects DNA synthesis in HeLa cells by inhibition of DNA polymerases. Cancer Res 50:7754

    Google Scholar 

  20. Kielian MC, Cohn ZA (1982) Intralysosomal accumulation of polyanions: II. Polyanion internalization and its influence on lysosomal pH and membrane fluidity. J Cell Biol 93:875

    Google Scholar 

  21. Kielian MC, Steinman RM, Cohn ZA (1982) Intralysosomal accumulation of polyanions: I. Fusion of pinocytic and phagocytic vacuoles with secondary lysosomes. J Cell Biol 93:866

    Google Scholar 

  22. Kopp R, Pfeiffer A (1990) Suramin alters phosphoinositide synthesis and inhibits growth factor receptor binding in HT 29 cells. Cancer Res 50:6490

    Google Scholar 

  23. Layton D, Azzi A (1974) Suramin: a potent inhibitor of the calcium transport in sarcoplasmic reticulum. Biochem Biophys Res Commun 59:322

    Google Scholar 

  24. Mahoney CW, Azzi A, Huang KP (1990) Effects of suramin, an anti-human immunodeficiency virus reverse transcriptase agent, on protein kinase C. J Biol Chem 265:5424

    Google Scholar 

  25. McDonald K, Horne I, Stein CA, LaRocca RV, Myers CE (1988) Circulating glycosaminoglycan anticoagulants associated with suramin treatment. Blood 71:273

    Google Scholar 

  26. Mitsuya H, Popovic M, Yarchoan R, Matsushita S, Gauo RC, Broder S (1984) Suramin protection of T cells in vitro against infectivity and cytopathic effect of HTLV-III. Science 226:172

    Google Scholar 

  27. Moriyama Y, Nelson N (1988) Inhibition of vacuolar H+-ATPases by fusidic acid and suramin. FEBS Lett 234:383

    Google Scholar 

  28. Nakajima M, DeChavigny A, Johnson CE, Hamada JI, Stein CA, Nicolson GL (1991) Suramin. A potent inhibitor of melanoma heparanase and invasion. J Biol Chem 266:9661

    Google Scholar 

  29. Ono K, Nakane H, Fukushima M (1988) Differential inhibition of various deoxyribonucleic and ribonucleic acid polymerases by suramin. Eur J Biochem 172:349

    Google Scholar 

  30. Pollak M, Richard M (1990) Suramin blockade of insulin like growth factor I-stimulated proliferation of human osteosarcoma cells. J Natl Cancer Inst 82:1349

    Google Scholar 

  31. Rago R, Mitchen J, Cheng A-L, Oberley T, Wilding G (1991) Disruption of cellular energy balance by suramin in intact human prostatic carcinoma cells, a likely antiproliferative mechanism. Cancer Res 51:6629

    Google Scholar 

  32. Spigelman Z, Dowers A, Kennedy S, Disorbon D, O'Brien M, Barr R, McCaffrey R (1987) Antiproliferative effects of suramin on lymphoid cells. Cancer Res 47:4694

    Google Scholar 

  33. Stein CA, LaRocca RV, Thomas N, McAtee N, Myers CE (1989) Suramin: an anticancer drug with a unique mechanism of action. J Clin Oncol 7:499

    Google Scholar 

  34. Waring MJ (1965) The effects of antimicrobial agents on ribonucleic acid polymerase. Mol Pharmacol 1:1

    Google Scholar 

  35. Williams LT, Tremble PM, Lavin MF, Sunday ME (1984) Plateletderived growth factor receptors form a high affinity state in membrane preparations. J Biol Chem 259:5287

    Google Scholar 

  36. Zabrenetzky VS, Kohn EC, Roberts DD (1990) Suramin inhibits laminin- and thrombospondin-mediated melanoma cell adhesion and migration and binding of these adhesive proteins to sulfatide. Cancer Res 50:5937

    Google Scholar 

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Larsen, A.K. Suramin: an anticancer drug with unique biological effects. Cancer Chemother. Pharmacol. 32, 96–98 (1993). https://doi.org/10.1007/BF00685609

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  • DOI: https://doi.org/10.1007/BF00685609

Keywords

  • Cancer Research
  • Biologic Effect
  • Antitumor Activity
  • Anticancer Drug
  • Drug Combination