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Cancer Chemotherapy and Pharmacology

, Volume 10, Issue 3, pp 161–166 | Cite as

Interactions of human leukocyte interferon with vinca alkaloids and other chemotherapeutic agents against human tumors in clonogenic assay

  • Matti S. Aapro
  • David S. Alberts
  • Sydney E. Salmon
Original Articles Interferon Vinblastine Clonogenic Assay

Summary

Purified human leukocyte interferon produced by recombinant techniques (IFN-αA) was tested in vitro with chemotherapeutic drugs, vinblastine (VLB), vincristine (VCR), vindesine (VDS), vinzolidine (VZL), cis-platinum (PLAT), doxorubicin (DOXO), etoposide (VP-16), and melphalan (MEL).

The activity of these agents alone or in combination was tested against various human tumor cell lines, using a modified soft agar clonogenic assay. Three human tumor cell lines (myeloma, RPMI 8226; breast, MCF-7; and colon, WiDR) showed sensitivity to these agents at clinically achievable drug concentrations. Statistically significant synergistic activity against in vitro colony formation was observed with the combination of VLB and IFN-αA. An additive or sub-additive effect was usually observed with the other agents tested. Continuous exposure of the 8226 myeloma cell line to both IFN-αA and PLAT showed evidence of a more significant potentiation. It is hypothesized that the synergistic effect observed between VLB and IFN-αA is due to some of their common mechanisms of action.

Keywords

Alkaloid Myeloma Etoposide Myeloma Cell Vinblastine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Alberts DS, Chen HSG, Salmon SE (1980) In vitro drug assay: pharmacologic considerations. In: Salmon SE (ed) Cloning of human tumor stem cells. Alan R Liss, New York, pp 197–207Google Scholar
  2. 2.
    Alberts DS, Salmon SE, Chen HSG, Moon TE, Young L, Surwit EA (1981) Pharmacologic studies of anticancer drugs using the human tumor stem cell assay. Cancer Chemother Pharmacol 6:253–264Google Scholar
  3. 3.
    Ambrus JL, Biddle W, Montagna RA, Leong SS, Horoszewicz J, Gastpar H, Ambrus CM (1982) Potentiation of interferon effect in tissue culture and nu/nu mice by pyrimido-pyrimidine derivatives. (Abstract) Proc Am Assoc Cancer Res, p 189Google Scholar
  4. 4.
    Baron S, Kleyn KM, Russell JK, Blalock JE (1981) Retinoic acid: enhancement of a tumor and inhibition of interferon's antitumor action. J Natl Cancer Inst 67:95–98Google Scholar
  5. 5.
    Blum RH, Frei E III, Holland JF (1982) Principles of dose, schedule and combination chemotherapy. In: Holland JF, Frei E III (eds) Cancer medicine, 2nd edn, Lea & Febiger, Philadelphia, pp 730–752Google Scholar
  6. 6.
    Bourgeade MF, Chany C, Merigan TC (1980) Type I and II interferons: differential antiviral actions in transformed cells. J Gen Virol 46:449–454Google Scholar
  7. 7.
    Bradley EC, Ruscetti FW (1981) Effect of fibroblast, lymphoid and myeloid interferons on human tumor colony formation in vitro. Cancer Res 41:244–249Google Scholar
  8. 8.
    Brostrom LA (1980) The combined effect of interferon and methotrexate on human osteosarcoma and lymphoma cell lines. Cancer Lett 10:83–90Google Scholar
  9. 9.
    Cesario TC, Slater LM (1980) Diminished antiviral effect of human interferon in the presence of therapeutic concentrations of antineoplastic agents. Infect Immun 27:842–845Google Scholar
  10. 10.
    Chirigos MA, Pearson JW (1973) Cure of murine leukemia with drug and interferon treatment. J Natl Cancer Inst 51:1367–1368Google Scholar
  11. 11.
    Drewinko B, Loo TL, Brown B, Gottlieb JA, Freireich EJ (1976) Combination chemotherapy in vitro with adriamycin. Observations of additive, antagonistic, and synergistic effects when used in two-drug combinations on cultured human lymphoma cells. Cancer Biochem Biophys 1:187–195Google Scholar
  12. 12.
    Epstein LB (1979) The comparative biology of immune and classical interferons. In: Cohen S, Pick E, Oppenheim JJ (eds) Biology of the lymphokines. Academic Press, New York, pp 443–514Google Scholar
  13. 13.
    Epstein LB, Shen JT, Abele JS, Reese CC (1980a) Sensitivity of human ovarian carcinoma cells to interferon and other antitumor agents as assessed by an in vitro semisolid agar technique. Ann NY Acad Sci 3509:228–244Google Scholar
  14. 14.
    Epstein LB, Shen JT, Abele JS, Reese CC (1980b) Further experience in testing the sensitivity of human ovarian carcinoma cells to interferon in an in vitro semisolid agar culture system: comparison of solid and ascitic forms of the tumor. Prog Clin Biol Res 48:277–290Google Scholar
  15. 15.
    Evinger M, Rubinstein M, Pestka S (1980) Growth-inhibitory and antiviral activity of purified leukocyte interferon. Ann NY Acad Sci 350:399–404Google Scholar
  16. 16.
    Fleischmann WR (1982) Potentiation of the direct anticellular activity of mouse interferons: mutual synergism and interferon concentration dependence. Cancer Res 42:869–875Google Scholar
  17. 17.
    Friedman RM (1980) Interferon: Interactioins with cell surfaces. In: Gresser I (ed) Interferon 1979, vol 1. Academic Press, London, pp 53–72Google Scholar
  18. 18.
    Gerfaux J, Rousset S, Chany-Fournier F, Chany C (1981) Interferon effect on collagen and fibronectin distribution in the extracellular matrix of murine sarcoma virus-transformed cells. Cancer Res 41:3629–3634Google Scholar
  19. 19.
    Goeddel DV, Yelverton E, Ullrich A, Heyneker HL, Miozzari G, Holmes W, Seeburg PH, Dull T, May L, Stebbing N, Crea R, Maeda S, McCandliss R, Sloma A, Tabor JM, Gross M, Familletti PC, Pestka S (1980) Human leukocyte interferon produced by E. coli is biologically active. Nature 287:411–416Google Scholar
  20. 20.
    Gresser I, Tovey MG (1978) Antitumor effects of interferon. Biochim Biophys Acta 516:231–247Google Scholar
  21. 21.
    Gresser I, Maury C, Brouty-Boye D (1972) Mechanism of the antitumor effect of interferon in mice. Nature 239:167–168Google Scholar
  22. 22.
    Gresser I, Maury C, Tovey M (1978) Efficacy of combined interferon cyclophosphamide therapy after diagnosis of lymphoma in AKR mice. Eur J Cancer 14:97–99Google Scholar
  23. 23.
    Gutterman JU, Fein S, Quesada J, Horning SJ, Levine JF, Alexanian R, Bernhardt L, Kramer M, Spiegel H, Colburn W, Trown P, Merigan T, Dziewanowska Z (1982) Recombinant leukocyte A interferon: pharmacokinetics, single-dose tolerance and biologic effects in cancer patients. Ann Intern Med 96:549–556Google Scholar
  24. 24.
    Hamburger AW, Salmon SE (1977) Primary bioassay of human tumor stem cells. Science 197:461–463Google Scholar
  25. 25.
    Havell EA, Vilcek J (1975) Inhibition of interferon secretion by vinblastine. J Cell Biol 64:716–719Google Scholar
  26. 26.
    Horning SJ, Levine JF, Miller RA, Rosenberg SA, Merigan TC (1982) Clinical and immunologic effects of recombinant leukocyte A interferon in eight patients with advanced cancer. JAMA 247:1718–1722Google Scholar
  27. 27.
    Ito M, Buffett RF (1981) Cytocidal effects of purified human fibroblast interferon on tumor cells in vitro. J Natl Cancer Inst 66:819–825Google Scholar
  28. 28.
    Maeda S, McCandliss R, Gross M, Sloma A, Familletti PC, Tabor JM, Evinger M, Levy WP, Pestka S (1980) Construction and identification of bacterial plasmids containing nucleotide sequence for human leukocyte interferon. Proc Natl Acad Sci USA 77:7010–7013Google Scholar
  29. 29.
    Momparler RL (1980) In vitro systems for evaluation of combination chemotherapy. Pharmacol Ther 8:21–35Google Scholar
  30. 30.
    Owellen RJ, Hartke CA, Dickerson RM, Hains FO (1976) Inhibition of tubulin-microtubule polymerization by drugs of the vinca alkaloid class. Cancer Res 36:1499–1502Google Scholar
  31. 31.
    Paul J (1975) Cell and tissue culture, 5th edn. Churchill-Livingston, London, p 95Google Scholar
  32. 32.
    Pfeffer LM, Wang E, Tamm I (1980) Interferon effects on microfilament organizatioin, cellular fibronectin distribution and cell motility in human fibroblasts. J Cell Biol 85:9–17Google Scholar
  33. 33.
    Salmon SE (ed) (1980a) Cloning of human tumor stem cells. Alan R Liss, New YorkGoogle Scholar
  34. 34.
    Salmon SE (1980b) Applications of the human tumor stem cell assay to new drug evaluation and screening. In: Salmon SE (ed) Cloning of human tumor stem cells. Alan R Liss, New York, p 291Google Scholar
  35. 35.
    Salmon SE, Durie BGM, Young L, Liu R, Trown PW, Stebbing N. (1983) Effects of cloned human leukocyte interferons in the human tumor stem cell assay. J Clin Oncol 1(3):217–225Google Scholar
  36. 36.
    Schabel FM, Laster WR, Trader MW, Mowshowitz SL, Smith GD (1982) Anticancer activity of mouse interferon alone and in combination with cis-dichlorodiammineplatinum II or mitomycin-C against leukemia P388 in mice. (Abstract) Proc Am Assoc Cancer Res, p 190Google Scholar
  37. 37.
    Slater LM, Wetzel MW, Cesario T (1981) Combined inteferon-antimetabolite therapy of murine L1210 leukemia. Cancer 48:5–9Google Scholar
  38. 38.
    Staehelin T, Hobbs DS, Kung HF, Lai CY, Pestka S (1981) Purification and characterization of recombinant human leukocyte interferon (IFLrA) with monoclonal antibodies. J Biol Chem 256:9750–9754Google Scholar
  39. 39.
    Steel GG (1979) Terminology in the description of drug-radiation interactions. Int J Rad/Onc Biol Phys 5:1145–1150Google Scholar
  40. 40.
    Tsuruo T, Iida H, Tsukagoshi S, Sakurai Y (1981) Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res 41:1967–1972Google Scholar
  41. 41.
    Valeriote F, Lin HS (1975) Synergistic interaction of anticancer agents: a cellular perspective. Cancer Chem Rep 59:895–900Google Scholar
  42. 42.
    Von Hoff DD, Casper J, Bradley E Jones D, Makuch R (1981) Association between human tumor colony forming assay results and response of an individual patient's tumor to chemotherapy. Am J Med 70:1027–1032Google Scholar
  43. 43.
    Von Hoff DD, Gutterman JU, Portnoy B, Coltman CA (1982). Activity of human leukocyte interferon in a human tumor cloning system. Cancer Chemother Pharmacol 8:99–103Google Scholar
  44. 44.
    Wilson L, Bamburg JR, Mizel SB, Grisham LM, Creswell KM (1974) Interaction of drugs with microtubule proteins. Fed Proc 33(2):158–166Google Scholar

Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • Matti S. Aapro
    • 1
  • David S. Alberts
    • 1
  • Sydney E. Salmon
    • 1
  1. 1.Section of Hematology and Oncology, Department of Medicine and the Cancer CenterUniversity of Arizona College of MedicineTucsonUSA

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