Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Antitumor activity of new anthracycline analogues in combination with interferon alfa

  • 26 Accesses

  • 5 Citations

Summary

Combinations of recombinant interferon alfa2 (IFN-α2) with doxorubicin, 4′-epidoxorubicin, 4′-deoxydoxorubicin, or 4-demethoxydaunorubicin were tested for antiproliferative activity against a panel of human tumor cell lines in a human tumor clonogenic assay. The histologies of the cell lines were ovary, cervix, breast, and melanoma. Each of the cytotoxic compounds showed dose-dependent antiproliferative effects against each of the cell lines, and the results indicated that doxorubicin derivatives were consistently more potent than the parent drug. In all instances, 4-demethoxydaunorubicin was the most potent derivative, requiring 2–20 times less drug to inhibit 70% of tumor colony formation. Combinations of IFN-α2, with doxorubicin or its derivatives may show additive or synergistic antiproliferative activity against certain tumor cell lines. The ovarian carcinoma cell line, BG-1, responded synergistically to each of the four compounds in combination with IFN-α2. The cervical carcinoma cell line, CaSki, and the breast carcinoma line, MCF-7, responded to the combinations in a manner best described as additive. In the melanoma line, SK-Mel-28, the drugs were found to be subadditive or even antagonistic. While the potency of the anthracyline derivatives ranked consistently across the different cell lines, the synergistic interaction with IFN-α2 is a cell line-specific phenomenon unrelated to sensitivity to either anthracyclines or interferon.

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

References

  1. 1.

    Arcamone R (1985) Properties of antitumor anthracylines and new developments in their application. Cancer Res 45: 5995

  2. 2.

    Capranico G, Dasdia T, Zunino F (1985) Comparison of doxorubicin-induced DNA damage in doxorubicin-sensitive and-resistant P388 murine leukemia cells. Int J Cancer 37: 227

  3. 3.

    Carey T, Takahashi T, Resnick LA, Oettgen HF, Old LJ (1976) Cell surface antigens of human malignant melanoma: mixed hemadsorption assays for humoral immunity to cultured autologous melanoma cells. Proc Natl Cancer Inst 45: 107

  4. 4.

    Cersosimo RJ, Hong WK (1986) Epirubicin: a review of the pharmacology, clinical activity, and adverse effects of an adriamycin analogue. J Clin Oncol 4: 425

  5. 5.

    Cummings J, McArdle CS (1986) Studies on the in vivo disposition of adriamycin in human tumors which exhibit different responses to the drug. Br J Cancer 53: 835

  6. 6.

    Di Marco A, Zunino F, Silvestrini R, Gambarucci G, Gambetto RA (1971) Interaction of some daunomycin derivatives with deoxyribonucleic acid and their biological activity. Biochem Pharmacol 20: 1323

  7. 7.

    Garewal HS, Robertone A, Salmon SE, Jones SE, Alberts DS, Brooks B (1984) Phase I trial of esorubicin (4′-deoxydoxorubicin). J Clin Oncol 2: 1043

  8. 8.

    Goldin A, Vendetti JM, Geran R (1985) The effectiveness of the anthracycline analog 4′-epidoxorubicin in the treatment of experimental tumors: a review. Invest New Drugs 3: 3

  9. 9.

    Hamburger AW, Salmon SE (1977) Primary bioassay of human tumor stem cells. Science 197: 461

  10. 10.

    Kangas L, Cantell K, Gronroos M, Maenpaa J, Perila M (1985) Antitumor effects of interferons, cytostatic drugs and their combinations in subrenal capsule assay (SRCA). Ann Chir Gynaecol [Suppl] 199: 60

  11. 11.

    Namba M, Yamamoto S, Tanaka H, Kanamori T, Nobuhara M, Kimoto T (1984) In vitro and in vivo studies on potentiation of cytotoxic effects of anticancer drugs or cobalt-60 gamma rays by interferon on human neoplastic cells. Cancer 54: 2262

  12. 12.

    Patillo RA, Husso RO, Story MT, Ruckert ACF, Shalaby MR, Mattingly RF (1977) Tumor antigen and human chorionic gonadotropin in CaSki cells: a new epidermoid cervical cancer line. Science 196: 1456

  13. 13.

    Pommier Y, Schwartz RE, Zwelling LA, Kerrigan D, Mattern MR, Charcosset JY, Jacquemin-Sablon A, Kohn KW (1986) Reduced formation of protein-associated DNA strand breaks in Chinese hamster cells resistant to topoisomerase II inhibitors. Cancer Res 46: 611

  14. 14.

    Salmon SE, Hamburger AW, Soehnlen B, Durie BGM, Alberts DS, Moon TE (1978) Quantitation of differential sensitivity of human tumor stem cells to anticancer drugs. N Engl J Med 298: 1321

  15. 15.

    Salmon SE, Liu R, Casazza AM (1981) Evaluation of new anthracycline analogs with the human tumor stem cell assay. Cancer Chemother Pharmacol 6: 103

  16. 16.

    Salmon SE, Young L, Leibowitz J, Thomson S, Einsphar J, Tong T, Moon TE (1984) Evaluation of an automated image analysis system for counting human tumor colonies. Int J Cell Cloning 2: 142

  17. 17.

    Sessa C, Bosia L, Kaplan S, Pusterla C, Varini M, Cavalli F (1984) Phase I trial of 4′-deoxydoxorubicin given weekly. Invest New Drugs 2: 369

  18. 18.

    Shoemaker RH, Wohpert-DeFilippes MK, Kern DH, Lieber MM, Makuch RW, Melnick NR, Miller WT, Salmon SE, Simon RM, Venditti JM, VonHoff DD (1985) Application of a human tumor colony forming assay to new drug screening. Cancer Res 45: 2145

  19. 19.

    Sigfried JM, Sartorelli AC, Tritton TR (1983) Evidence for the lack of relationship between inhibition of nucleic acid synthesis and cytotoxicity of adriamycin. Cancer Biochem Biophys 6: 137

  20. 20.

    Soule HD, Vasquez J, Long A, Albert S, Brennan M (1973) A human cell line from a pleural effusion derived from a breast carcinoma. J Natl Cancer Inst 51: 1409

  21. 21.

    Twentyman PR, Fox NE, Wright KA, Workman P, Broadhurst MJ, Martin JA, Bleehen NM (1986) The in vitro effects and cross-resistance patterns of some novel anthracyclines. Br J Cancer 53: 585

  22. 22.

    Welander CE, Morgan TM, Homesley HD, Trotta PP, Spiegel RJ (1985) Combined recombinant interferon alpha 2 and cytotoxic agents studied in a clonogenic assay. Int J Cancer 35: 721

Download references

Author information

Additional information

Supported by a grant from Farmitalia Carlo Erba, Milan, Italy

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Berens, M.E., Saito, T., Welander, C.E. et al. Antitumor activity of new anthracycline analogues in combination with interferon alfa. Cancer Chemother. Pharmacol. 19, 301–306 (1987). https://doi.org/10.1007/BF00261477

Download citation

Keywords

  • Melanoma
  • Doxorubicin
  • Carcinoma Cell Line
  • Ovarian Carcinoma
  • Human Tumor Cell Line