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Suramin Inhibits Not Only Tumor Growth and Metastasis but Also Angiogenesis in Experimental Pancreatic Cancer

  • Published:
Journal of Gastrointestinal Surgery

Abstract

Suramin inhibits the proliferation of several human tumors in vivo and in vitro. In this study, the effects of Suramin on proliferation and angiogenesis were investigated in human pancreatic cancer cell lines and in an orthotopic nude mouse model of human pancreatic cancer. The effects of Suramin on proliferation, viability, cell cycle, and apoptosis were studied in five human pancreatic cancer cell lines. Suramin inhibited the proliferation of pancreatic cancer cells in a dose-dependent manner and reduced viability at high concentrations. Cell cycle analysis revealed a decreased S-phase fraction in most cell lines, whereas the apoptotic fraction was not notably different. In vivo treatment with Suramin significantly reduced pancreatic tumor size (MiaPaCa-2, −74%; AsPC-1, −41%; and Capan-1, −49%) and metastatic spread (MiaPaCa-2, −79%; AsPC-1, −34%; and Capan, −38%). As a parameter for angiogenic activity, vascular endothelial growth factor (VEGF) secretion was measured, revealing reduced VEGF concentrations under Suramin treatment in both cell culture medium and ascites. Also, microvessel density quantified in primary tumors was reduced in animals treated with Suramin. Therefore, Suramin inhibits the proliferation of human pancreatic cancer in vitro and in vivo. The therapeutic effects seem to involve cell cycle kinetics and may be in part related to the antiangiogenic action of the drug.

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References

  1. Parker SL, Tong T, Bolden S, Wingo PA. Cancer statistics, 1997. CA Cancer J Clin 1997;47(1):5–27.

    PubMed  CAS  Google Scholar 

  2. Kabbinavar F, Hurwitz HI, Fehrenbacher L, Meropol NJ, Novotny WF, Lieberman G, et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 2003;21(1):60–65.

    Article  PubMed  CAS  Google Scholar 

  3. Fiedler W, Mesters R, Tinnefeld H, Loges S, Staib P, Duhrsen U, et al. A phase 2 clinical study of SU5416 in patients with refractory acute myeloid leukemia. Blood 2003;102(8):2763–2767.

    Article  PubMed  CAS  Google Scholar 

  4. Hawking F. Suramin: with special reference to onchocerciasis. Adv Pharmacol Chemother 1978;15:289–322.

    Article  PubMed  CAS  Google Scholar 

  5. Coffey RJ Jr, Leof EB, Shipley GD, Moses HL. Suramin inhibition of growth factor receptor binding and mitogenicity in AKR-2B cells. J Cell Physiol 1987;132(1):143–148.

    Article  PubMed  CAS  Google Scholar 

  6. Vogelzang NJ, Karrison T, Stadler WM, Garcia J, Cohn H, Kugler J, et al. A phase II trial of Suramin monthly × 3 for hormone-refractory prostate carcinoma. Cancer 2004;100(1):65–71.

    Article  PubMed  CAS  Google Scholar 

  7. Gagliardi A, Hadd H, Collins DC. Inhibition of angiogenesis by Suramin. Cancer Res 1992;52(18):5073–5075.

    PubMed  CAS  Google Scholar 

  8. Pesenti E, Sola F, Mongelli N, Grandi M, Spreafico F. Suramin prevents neovascularisation and tumour growth through blocking of basic fibroblast growth factor activity. Br J Cancer 1992;66(2):367–372.

    PubMed  CAS  Google Scholar 

  9. Ingber D, Fujita T, Kishimoto S, Sudo K, Kanamaru T, Brem H, et al. Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth. Nature 1990;348(6301):555–557.

    Article  PubMed  CAS  Google Scholar 

  10. Hotz HG, Reber HA, Hotz B, Yu T, Foitzik T, Buhr HJ, et al. An orthotopic nude mouse model for evaluating pathophysiology and therapy of pancreatic cancer. Pancreas 2003;26(4):e89–e98.

    Article  PubMed  Google Scholar 

  11. Walz TM, Abdiu A, Wingren S, Smeds S, Larsson SE, Wasteson A. Suramin inhibits growth of human osteosarcoma xenografts in nude mice. Cancer Res 1991;51(13):3585–3589.

    PubMed  CAS  Google Scholar 

  12. Weidner N. Tumoural vascularity as a prognostic factor in cancer patients: the evidence continues to grow. J Pathol 1998;184(2):119–122.

    Article  PubMed  CAS  Google Scholar 

  13. La Rocca RV, Stein CA, Myers CE. Suramin: prototype of a new generation of antitumor compounds. Cancer Cells 1990;2(4):106–115.

    PubMed  Google Scholar 

  14. Choe G, Kim WH, Park JG, Kim YI. Effect of Suramin on differentiation of human stomach cancer cell lines. J Korean Med Sci 1997;12(5):433–442.

    PubMed  CAS  Google Scholar 

  15. Shin R, Naomoto Y, Kamikawa Y, Tanaka N, Orita K. Effect of Suramin on human esophageal cancer cells in vitro and in vivo. Scand J Gastroenterol 1997;32(8):824–828.

    PubMed  CAS  Google Scholar 

  16. Fujiuchi S, Ohsaki Y, Kikuchi K. Suramin inhibits the growth of non-small-cell lung cancer cells that express the epidermal growth factor receptor. Oncology 1997;54(2):134–140.

    Article  PubMed  CAS  Google Scholar 

  17. Takano S, Gately S, Engelhard H, Tsanaclis AM, Brem S. Suramin inhibits glioma cell proliferation in vitro and in the brain. J Neuro-oncol 1994;21(3):189–201.

    Article  CAS  Google Scholar 

  18. Qiao L, Pizzolo JG, Melamed MR. Effects of Suramin on expression of proliferation associated nuclear antigens in DU-145 prostate carcinoma cells. Biochem Biophys Res Commun 1994;201(2):581–588.

    Article  PubMed  CAS  Google Scholar 

  19. Bocci G, Danesi R, Benelli U, Innocenti F, Di Paolo A, Fogli S, et al. Inhibitory effect of Suramin in rat models of angiogenesis in vitro and in vivo. Cancer Chemother Pharmacol 1999;43(3):205–212.

    Article  PubMed  CAS  Google Scholar 

  20. Zeng J, Mei W, Huang H, Li X, Kong P. Inhibitory effect of angiogenesis inhibitor TNP-470 on human ACHN renal cell carcinoma. J Huazhong Univ Sci Technolog Med Sci 2002;22(4):331–333.

    Article  PubMed  CAS  Google Scholar 

  21. Arisawa C, Kageyama Y, Kawakami S, Kihara K. TNP-470 combined with nicardipine suppresses in vivo growth of PC-3, a human prostate cancer cell line. Urol Oncol 2002;7(6):229–234.

    Article  PubMed  CAS  Google Scholar 

  22. Logothetis CJ, Wu KK, Finn LD, Daliani D, Figg W, Ghaddar H, et al. Phase I trial of the angiogenesis inhibitor TNP-470 for progressive androgen-independent prostate cancer. Clin Cancer Res 2001;7(5):1198–1203.

    PubMed  CAS  Google Scholar 

  23. Cattelan AM, Trevenzoli M, Aversa SM. Recent advances in the treatment of AIDS-related Kaposi’s sarcoma. Am J Clin Dermatol 2002;3(7):451–462.

    Article  PubMed  Google Scholar 

  24. Kruger EA, Figg WD. TNP-470: an angiogenesis inhibitor in clinical development for cancer. Expert Opin Investig Drugs 2000;9(6):1383–1396.

    Article  PubMed  CAS  Google Scholar 

  25. Hotz HG, Reber HA, Hotz B, Sanghavi PC, Yu T, Foitzik T, et al. Angiogenesis inhibitor TNP-470 reduces human pancreatic cancer growth. J Gastrointest Surg 2001;5(2):131–138.

    Article  PubMed  CAS  Google Scholar 

  26. Waltenberger J, Mayr U, Frank H, Hombach V. Suramin is a potent inhibitor of vascular endothelial growth factor. A contribution to the molecular basis of its antiangiogenic action. J Mol Cell Cardiol 1996;28(7):1523–1529.

    Article  PubMed  CAS  Google Scholar 

  27. Garcia-Schurmann JM, Schulze H, Haupt G, Pastor J, Allolio B, Senge T. Suramin treatment in hormone- and chemotherapy-refractory prostate cancer. Urology 1999;53(3):535–541.

    Article  PubMed  CAS  Google Scholar 

  28. Marchetti D, Reiland J, Erwin B, Roy M. Inhibition of heparanase activity and heparanase-induced angiogenesis by Suramin analogues. Int J Cancer 2003;104(2):167–174.

    Article  PubMed  CAS  Google Scholar 

  29. Meyers MO, Gagliardi AR, Flattmann GJ, Su JL, Wang YZ, Woltering EA. Suramin analogs inhibit human angiogenesis in vitro. J Surg Res 2000;91(2):130–134.

    Article  PubMed  CAS  Google Scholar 

  30. Song S, Yu B, Wei Y, Wientjes MG, Au JL. Low-dose Suramin enhanced paclitaxel activity in chemotherapy-naive and paclitaxel-pretreated human breast xenograft tumors. Clin Cancer Res 2004;10(18 Pt 1):6058–6065.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Charité - Medical School Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany

    Sarah Bhargava, Birgit Hotz, Heinz J. Buhr & Hubert G. Hotz

  2. Department of Surgery, UCLA School of Medicine, Los Angeles, CA, USA

    O. Joe Hines & Howard A. Reber

Authors
  1. Sarah Bhargava
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  2. Birgit Hotz
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  3. O. Joe Hines
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  4. Howard A. Reber
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  5. Heinz J. Buhr
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  6. Hubert G. Hotz
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Corresponding author

Correspondence to Hubert G. Hotz.

Additional information

Supported by the R.S. Hirshberg Foundation and the Deutsche Forschungsgemeinschaft (Grant HO 1843/2-1 & 1843/3-1).

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Bhargava, S., Hotz, B., Hines, O.J. et al. Suramin Inhibits Not Only Tumor Growth and Metastasis but Also Angiogenesis in Experimental Pancreatic Cancer. J Gastrointest Surg 11, 171–178 (2007). https://doi.org/10.1007/s11605-006-0081-z

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  • DOI: https://doi.org/10.1007/s11605-006-0081-z

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