Skip to main content
SpringerLink
Log in

N-methylformamide affects spontaneous metastases of 3LL lines and increases natural killer activity of tumor-bearing mice

  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

The antitumor activity of the polar solvent N-methylformamide (NMF) was evaluated on three lines derived from the Lewis lung carcinoma (3 LL), endowed with different metastatic potential. Two administration schedules were tested, these being repeated regimens of NM F (200 mg/kg per dose) for 12 consecutive days, starting 24 h or 6–10 days after tumor implantation (early or late treatment, respectively). The results of the present work can be summarized as follows: (1) NMF regimens did not greatly affect tumor growth behavior of 3LL lines; conversely, they markedly influenced their spontaneous colonizing ability in the lungs, either by delaying early metastatic spread or by reducing the number and size of pulmonary metastases already implanted. (2) A significant increase of NK cell activity during and after early treatment with NMF was observed in the more-metastasizing lines, thus suggesting the possibility of an immunomodulating effect of NMF.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bennett, D. C., Dexter, T. J., Ormerod, E. J., and Hart, I. R., 1986, Increased experimental metastatic capacity of a murine melanoma following induction of differentiation. Cancer Research, 46, 3239–3244.

    Google Scholar 

  2. Christensen, T. G., Burke, B., Dexter, D. L., and Zamcheck, N., 1985, Ultrastructural evidence of dimethylformamide-induced differentiation of cultured human colon carcinoma cells. Cancer, 56, 1559–1565.

    Google Scholar 

  3. Cikes, M. S., Friberg, S., and Klein, G., 1973, Progressive loss of H-2 antigens with concomitant increase of cell surface antigen(s) determined by Moloney leukemia virus in cultured murine lymphomas. Journal of the National Cancer Institute, 50, 347–362.

    Google Scholar 

  4. Dexter, D. L., Barbosa, J. A., and Calabresi, P., 1979, N,N-Dimethylformamideinduced alteration of cell culture characteristics and loss of tumorigenicity in cultured human colon carcinoma cells. Cancer Research, 39, 1020–1025.

    Google Scholar 

  5. Dukes, C. E., and Bussey, H. J. R., 1958, The spread of rectal cancer and its effect on prognosis. British Journal of Cancer, 12, 309–320.

    Google Scholar 

  6. Friedell, G. H., Bell, J. R., Burney, S. W., Soto, E. A., and Tiltman, A. J., 1976, Histopathology and classification of urinary bladder carcinoma. Urologic Clinics of North America, 3, 53–70.

    Google Scholar 

  7. Garaci, E., Mastino, A., Jezzi, T., Riccardi, C., and Favalli, C., 1987, Effect of in vivo administration of prostaglandins and interferon on natural killer activity and on B-16 melanoma growth in mice. Cellular Immunology, 106, 43–52.

    Google Scholar 

  8. Garaci, E., Mastino, A., and Favalli, C., 1988, Immunomodulatory effects of prostaglandins and thymic hormones. Advances in Immunomodulation, edited by B. Bizzini and E. Bonmassar (Rome, Milan: Pythagora Press), pp. 169–176.

    Google Scholar 

  9. Geran, R. I., Greenberg, N. H., MacDonald, M. M., Schumacher, A. M., and Abbott, B. J., 1972, Protocols for screening chemical agents and natural products against animal tumours and other biological systems. Cancer Chemotherapy Report, 3, 1–103.

    Google Scholar 

  10. Gescher, A., Gibson, N. W., Hickman, J. A., Langdon, S. P., Ross, D., and Atassi, G., 1982, N-Methylformamide: antitumor activity and metabolism in mice. British Journal of Cancer, 45, 843–850.

    Google Scholar 

  11. Gorelik, E., Wiltrout, R. H., Okumura, K., Habu, S., and Herberman, R. B., 1982, Role of NK cells in the control of metastatic spread and growth of tumor cells in mice. International Journal of Cancer, 30, 107–112.

    Google Scholar 

  12. Greco, C., Corsi, A., Caputo, M., Cavallari, A., and Calabresi, F., 1979, Cyclophosphamide and Iphosphamide against Lewis lung carcinoma: evaluation of toxic and therapeutic effects. Tumori, 65, 169–180.

    Google Scholar 

  13. Greco, C., Calabresi, F., Caputo, M., Sacchi, A., and zupi, G., 1980, Effect of bleomycin scheduling on lung metastases of 3LL and a subline of different metastatic potential. Metastasis, edited by K. Hellmann, P. Hilgard and S. Eccles (The Hague: Martinus Nijhoff), vol. 4, pp. 406–410.

    Google Scholar 

  14. Hanna, N., and Fidler, I. J., 1980, Role of natural killer cells in the destruction of circulating tumor emboli. Journal of the National Cancer Institute, 65, 801–809.

    Google Scholar 

  15. Hanna, N., 1980, Expression of metastatic potential of tumor cells in young nude mice is correlated with low levels of natural killer mediated cytotoxicity. International Journal of Cancer, 26, 675–680.

    Google Scholar 

  16. Herberman, R. B., Nunn, M. E., and Laurin, D. H., 1975, Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. I. Distribution of reactivity. International Journal of Cancer, 16, 216–221.

    Google Scholar 

  17. Herter, F. P., and Slanetz, C. A., 1982, Patterns and significance of lymphatic spread from cancer of the colon and rectum. Lymphatic System Metastasis, edited by L. Weiss, H. A. Gilbert and S. C. Ballon (Boston: G. K. Hall), pp. 275–307.

    Google Scholar 

  18. Iwakawa, M., Tofilon, P. J., Hunter, N., Stephens, L. C., and Milas, L., 1987, Antitumor and antimetastatic activity of the differentiating agent N-methylformamide in murine tumor systems. Clinical and Experimental Metastasis, 5(4), 289–300.

    Google Scholar 

  19. Kennedy, G. L., 1986, Biological effects of acetamide, formamide and their monomethyl and dimethyl derivatives. CRC Critical Reviews in Toxicology, 17 (2), 129–182.

    Google Scholar 

  20. Langdon, S. P., Hickman, J. A., Gescher, A., Stevens, M. F. G., Chubb, D., and Vickers, L. M., 1985, N-Methylformamide (NSC 3051): a potential candidate for combination chemotherapy. European Journal of Cancer and Clinical Oncology, 21 (6), 745–752.

    Google Scholar 

  21. Marx, L. J., 1987, Human trials of new cancer therapy begin. Science, 236, 778–779.

    Google Scholar 

  22. Meitner, P. A., Crabtree, G. W., Kajiji, S. M., and Calabresi, P., 1985, N-Methylformamide (NMF) delays metastasis of human pancreas cancer (HPC) in a nude mouse model. Proceeding of the American Association of Cancer Research, 26, 37.

    Google Scholar 

  23. Parhar, R. S., and Lala, P. K., 1985, Changes in the host natural killer cell population in mice during tumor development. II. The mechanism of suppression of NK activity. Cellular Immunology, 93, 265–279.

    Google Scholar 

  24. Planting, A. S., Klijn, J. G. M., Verweij, J., and Stoter, G., 1987, Phase II study on oral N-Methylformamide in metastatic colorectal cancer. Cancer Treatment Reports, 71 (12), 1293–1294.

    Google Scholar 

  25. Rowinsky, E. K., Noe, D. A., Orr, D. W., Grochow, L. B., Ettinger, D. S., and Donehower, R. C., 1988, Clinical pharmacology of oral and i.v. N-methylformamide: a pharmacologic basis for lack of clinical antineoplastic activity. Journal of the National Cancer Institute, 80, 671–678.

    Google Scholar 

  26. Sartorelli, A. C., 1985, Malignant cell differentiation as a potential therapeutic approach. British Journal of Cancer, 52, 293–302.

    Google Scholar 

  27. Spremulli, E. N., and Dexter, D. L., 1984, Polar solvents: a novel class of antineoplastic agents. Journal of Clinical Oncology, 2 (3), 227–241.

    Google Scholar 

  28. Sternberg, C. N., Yagoda, A., Scher, I., and Hollander, P., 1986, Phase II trial of N-methylformamide for advanced renal cell carcinoma. Cancer Treatment Reports, 70, 681–682.

    Google Scholar 

  29. Takenaga, K., 1984, Enhancement of lung-colonizing ability of cloned low-metastatic Lewis lung carcinoma cells by treatment with highly polar compound. International Journal of Cancer, 34, 83–89.

    Google Scholar 

  30. Thorn, R. M., and Herney, C. S., 1976, Kinetic analysis of target cell destruction by effector T cell. Delineation of parameters related to the frequency and lytic efficiency of killer cells. Journal of Immunology, 117, 2213–2219.

    Google Scholar 

  31. Tofilon, P. J., Vines, C. M., and Milas, L., 1986, N-methylformamide-mediated enhancement of in vitro tumor cell chemosensitivity. Cancer Chemotherapy and Pharmacology, 17, 269–273.

    Google Scholar 

  32. Tofilon, P. J., Vines, C. M., and Milas, L., 1987, The effects of N-methylformamide on artificial and spontaneous metastases from a murine hepatocarcinoma. British Journal of Cancer, 55, 239–243.

    Google Scholar 

  33. Zupi, G., Mauro, F., and Sacchi, A., 1980, Cloning in vitro and in vivo of Lewis lung carcinoma: properties and characteristics. British Journal of Cancer, 41 (suppl. IV), 309–311.

    Google Scholar 

  34. Zupi, G., Cavallari, A., Greco, C., and Sacchi, A., 1984, Lewis lung carcinoma lines with different metastatic behaviour: response to ICRF-159. Anticancer Research, 4, 91–95.

    Google Scholar 

  35. Zupi, G., Marangolo, M., Arancia, G., Greco, C., Laudonio, N., Iosi, F., Formisano, G., and Malorni, W., 1988, Modulation of the cytotoxic effect of 5-Fluorouracyl by N-methylformamide on a human colon carcinoma cell line. Cancer Research, 48, 6193–6200.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Experimental Chemotherapy Laboratory, Regina Elena Institute for Cancer Research, Rome, Italy

    C. Greco, D. Del Bufalo & G. Zupi

  2. Medical Physics and Expert Systems Laboratory, Regina Elena Institute for Cancer Research, Rome, Italy

    D. Giannarelli

  3. Medical Oncology Unit, City Hospital of Ravenna, Italy

    M. Marangolo

  4. Experimental Medicine Institute, National Council of Research, Rome, Italy

    M. P. Fuggetta

  5. Experimental Medicine and Biochemical Science Department, School of Medicine, II University of Rome, Italy

    C. Greco & E. Bonmassar

Authors
  1. C. Greco
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Del Bufalo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Giannarelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Marangolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. P. Fuggetta
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E. Bonmassar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G. Zupi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Greco, C., Del Bufalo, D., Giannarelli, D. et al. N-methylformamide affects spontaneous metastases of 3LL lines and increases natural killer activity of tumor-bearing mice. Clin Exp Metast 8, 153–163 (1990). https://doi.org/10.1007/BF00117788

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00117788

Keywords

Search

Navigation