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British Journal of Cancer logoLink to British Journal of Cancer
. 1992 Aug;66(2):281–286. doi: 10.1038/bjc.1992.257

The effects of ICRF-154 in combination with other anticancer agents in vitro.

Y Kano 1, T Narita 1, K Suzuki 1, M Akutsu 1, K Suda 1, S Sakamoto 1, Y Miura 1
PMCID: PMC1977796  PMID: 1503899

Abstract

We studied the effects of ICRF-154 in combination with 11 anticancer agents on four human leukaemia cell lines. Cells were incubated for 3 days in the presence of two drugs (ICRF-154 and one other), and cell growth inhibition was determined by MTT assay. Effects of drug combinations at the ID50 level were analysed using the isobologram method (Steel). In the lymphoblastic leukaemia cell lines, MOLT-3, HSB, and B-ALL, supra-additive effects were observed for ICRF-154 in combination with amsacrine, bleomycin, doxorubicin, and etoposide. Additive effects were observed for its combinations with cisplatin, CPT-11, cytosine arabinoside, 5-fluorouracil, mitomycin C, and vincristine. Sub-additive to protective effects were observed in combination with methotrexate. In an erythroleukaemia cell line, K-562, no drug showed supra-additive effects with ICRF-154, while sub-additive to protective effects were observed for ICRF-154 in combination with cisplatin and methotrexate. The other drugs showed additive effects with ICRF-154. These results indicate that the combined effects of ICRF-154 with other agents vary, depending on the cell line. Against lymphoid malignancies, ICRF-154 would be advantageous when administered simultaneously with many anticancer agents. Of such agents, amsacrine, bleomycin, doxorubicin, and etoposide are the most suitable, while methotrexate is least suitable for such combined treatment.

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Selected References

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  1. Adams R. A., Flowers A., Davis B. J. Direct implantation and serial transplantation of human acute lymphoblastic leukemia in hamsters, SB-2. Cancer Res. 1968 Jun;28(6):1121–1125. [PubMed] [Google Scholar]
  2. Chou T. C., Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 1984;22:27–55. doi: 10.1016/0065-2571(84)90007-4. [DOI] [PubMed] [Google Scholar]
  3. Creaven P. J., Allen L. M., Alford D. A. The bioavailability in man of ICRF-159 a new oral antineoplastic agent. J Pharm Pharmacol. 1975 Dec;27(12):914–918. doi: 10.1111/j.2042-7158.1975.tb10247.x. [DOI] [PubMed] [Google Scholar]
  4. Creighton A. M., Hellmann K., Whitecross S. Antitumour activity in a series of bisdiketopiperazines. Nature. 1969 Apr 26;222(5191):384–385. doi: 10.1038/222384a0. [DOI] [PubMed] [Google Scholar]
  5. Del Bino G., Darzynkiewicz Z. Camptothecin, teniposide, or 4'-(9-acridinylamino)-3-methanesulfon-m-anisidide, but not mitoxantrone or doxorubicin, induces degradation of nuclear DNA in the S phase of HL-60 cells. Cancer Res. 1991 Feb 15;51(4):1165–1169. [PubMed] [Google Scholar]
  6. Fischer V. W., Wang G. M., Hobart N. H. Mitigation of an anthracycline-induced cardiomyopathy by pretreatment with razoxane: a quantitative morphological assessment. Virchows Arch B Cell Pathol Incl Mol Pathol. 1986;51(4):353–361. doi: 10.1007/BF02899044. [DOI] [PubMed] [Google Scholar]
  7. Hellmann K., Newton K. A., Whitmore D. N., Hanham I. W., Bond J. V. Preliminary clinical assessment of I.C.R.F. 159 in acute leukaemia and lymphosarcoma. Br Med J. 1969 Mar 29;1(5647):822–824. doi: 10.1136/bmj.1.5647.822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Herman E. H., Witiak D. T., Hellmann K., Waravdekar V. S. Biological properties of ICRF-159 and related bis(dioxopiperazine) compounds. Adv Pharmacol Chemother. 1982;19:249–290. doi: 10.1016/s1054-3589(08)60025-3. [DOI] [PubMed] [Google Scholar]
  9. Hsiang Y. H., Hertzberg R., Hecht S., Liu L. F. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J Biol Chem. 1985 Nov 25;260(27):14873–14878. [PubMed] [Google Scholar]
  10. Ishida R., Miki T., Narita T., Yui R., Sato M., Utsumi K. R., Tanabe K., Andoh T. Inhibition of intracellular topoisomerase II by antitumor bis(2,6-dioxopiperazine) derivatives: mode of cell growth inhibition distinct from that of cleavable complex-forming type inhibitors. Cancer Res. 1991 Sep 15;51(18):4909–4916. [PubMed] [Google Scholar]
  11. Johnson D. H., Greco F. A., Strupp J., Hande K. R., Hainsworth J. D. Prolonged administration of oral etoposide in patients with relapsed or refractory small-cell lung cancer: a phase II trial. J Clin Oncol. 1990 Oct;8(10):1613–1617. doi: 10.1200/JCO.1990.8.10.1613. [DOI] [PubMed] [Google Scholar]
  12. Kano Y., Ohnuma T., Okano T., Holland J. F. Effects of vincristine in combination with methotrexate and other antitumor agents in human acute lymphoblastic leukemia cells in culture. Cancer Res. 1988 Jan 15;48(2):351–356. [PubMed] [Google Scholar]
  13. Kano Y., Sakamoto S., Kasahara T., Akutsu M., Inoue Y., Miura Y. Effects of amsacrine in combination with other anticancer agents in human acute lymphoblastic leukemia cells in culture. Leuk Res. 1991;15(11):1059–1066. doi: 10.1016/0145-2126(91)90112-7. [DOI] [PubMed] [Google Scholar]
  14. Kano Y., Suzuki K., Akutsu M., Suda K., Inoue Y., Yoshida M., Sakamoto S., Miura Y. Effects of CPT-11 in combination with other anti-cancer agents in culture. Int J Cancer. 1992 Feb 20;50(4):604–610. doi: 10.1002/ijc.2910500420. [DOI] [PubMed] [Google Scholar]
  15. Kubonishi I., Daibata M., Yano S., Isobe M., Kurosawa N., Nagumo H., Ogita Z., Ohyashiki J. H., Toyama K., Miyoshi I. Establishment of a new Epstein-Barr virus nuclear antigen-positive B-cell line, BALL-2, with t(8;14) (q24;q32) chromosome abnormality from B-cell acute lymphoblastic leukemia, L2. Am J Hematol. 1991 Jul;37(3):179–185. doi: 10.1002/ajh.2830370309. [DOI] [PubMed] [Google Scholar]
  16. LOEWE S. The problem of synergism and antagonism of combined drugs. Arzneimittelforschung. 1953 Jun;3(6):285–290. [PubMed] [Google Scholar]
  17. Lozzio C. B., Lozzio B. B. Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood. 1975 Mar;45(3):321–334. [PubMed] [Google Scholar]
  18. Minowada J., Onuma T., Moore G. E. Rosette-forming human lymphoid cell lines. I. Establishment and evidence for origin of thymus-derived lymphocytes. J Natl Cancer Inst. 1972 Sep;49(3):891–895. [PubMed] [Google Scholar]
  19. Monti E., Sinha B. K. Potentiation of doxorubicin cytotoxicity by (+)-1,2-bis-(3,5-dioxopiperazinyl-1-yl) propane (ICRF-187) in human leukemic HL-60 cells. Cancer Commun. 1990;2(4):145–149. doi: 10.3727/095535490820874551. [DOI] [PubMed] [Google Scholar]
  20. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
  21. Narita T., Koide Y., Yaguchi S., Kimura S., Izumisawa Y., Takase M., Inaba M., Tsukagoshi S. Antitumor activities and schedule dependence of orally administered MST-16, a novel derivative of bis(2,6-dioxopiperazine). Cancer Chemother Pharmacol. 1991;28(4):235–240. doi: 10.1007/BF00685528. [DOI] [PubMed] [Google Scholar]
  22. Narita T., Yaguchi S., Komatsu T., Takase M., Hoshino A., Inaba M., Tsukagoshi S. Antitumor activity of MST-16, a novel derivative of bis(2,6-dioxopiperazine), in murine tumor models. Cancer Chemother Pharmacol. 1990;26(3):193–197. doi: 10.1007/BF02897198. [DOI] [PubMed] [Google Scholar]
  23. Ohno R., Yamada K., Hirano M., Shirakawa S., Tanaka M., Oguri T., Kodera Y., Mitomo Y., Ikeda Y., Yokomaku S. Phase II study: treatment of non-Hodgkin's lymphoma with an oral antitumor derivative of bis(2,6-dioxopiperazine). J Natl Cancer Inst. 1992 Mar 18;84(6):435–438. doi: 10.1093/jnci/84.6.435. [DOI] [PubMed] [Google Scholar]
  24. Sampi K., Ogawa M., Maekawa T., Takaku F., Kuraishi Y., Ota K., Hirano M., Hoshino A., Shirakawa S., Kimura I. [Phase II study of VP-16 (capsule) in malignant lymphomas. A cooperative study]. Gan To Kagaku Ryoho. 1985 Feb;12(2):314–319. [PubMed] [Google Scholar]
  25. Sharpe H. B., Field E. O., Hellmann K. Mode of action of the cytostatic agent "ICRF 159". Nature. 1970 May 9;226(5245):524–526. doi: 10.1038/226524a0. [DOI] [PubMed] [Google Scholar]
  26. Steel G. G., Peckham M. J. Exploitable mechanisms in combined radiotherapy-chemotherapy: the concept of additivity. Int J Radiat Oncol Biol Phys. 1979 Jan;5(1):85–91. doi: 10.1016/0360-3016(79)90044-0. [DOI] [PubMed] [Google Scholar]
  27. Tanabe K., Ikegami Y., Ishida R., Andoh T. Inhibition of topoisomerase II by antitumor agents bis(2,6-dioxopiperazine) derivatives. Cancer Res. 1991 Sep 15;51(18):4903–4908. [PubMed] [Google Scholar]
  28. Tewey K. M., Chen G. L., Nelson E. M., Liu L. F. Intercalative antitumor drugs interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II. J Biol Chem. 1984 Jul 25;259(14):9182–9187. [PubMed] [Google Scholar]
  29. Valeriote F., Lin H. s. Synergistic interaction of anticancer agents: a cellular perspective. Cancer Chemother Rep. 1975 Sep-Oct;59(5):895–900. [PubMed] [Google Scholar]
  30. Wadler S., Green M. D., Muggia F. M. Synergistic activity of doxorubicin and the bisdioxopiperazine (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane (ICRF 187) against the murine sarcoma S180 cell line. Cancer Res. 1986 Mar;46(3):1176–1181. [PubMed] [Google Scholar]
  31. Woodman R. J., Cysyk R. L., Kline I., Gang M., Venditti J. M. Enhancement of the effectiveness of daunorubicin (NSC-82151) or adriamycin (NSC-123127) against early mouse L1210 leukemia with ICRF-159 (NSC-129943). Cancer Chemother Rep. 1975 Jul-Aug;59(4):689–695. [PubMed] [Google Scholar]
  32. Yang L., Rowe T. C., Liu L. F. Identification of DNA topoisomerase II as an intracellular target of antitumor epipodophyllotoxins in simian virus 40-infected monkey cells. Cancer Res. 1985 Nov;45(11 Pt 2):5872–5876. [PubMed] [Google Scholar]

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