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. 1986 May;53(5):585–594. doi: 10.1038/bjc.1986.100

The in vitro effects and cross-resistance patterns of some novel anthracyclines.

P R Twentyman, N E Fox, K A Wright, P Workman, M J Broadhurst, J A Martin, N M Bleehen
PMCID: PMC2001391  PMID: 3459509

Abstract

A range of new anthracyclines, structurally related to adriamycin (ADM), has been synthesised and studied in vitro. Three compounds described in this paper (Ro 31-1215; Ro 31-1741; Ro 31-2035) are all 4-demethoxyanthracyclines. In the mouse mammary tumour cell line, EMT6/Ca/VJAC, using a 1 h drug exposure followed by colony formation as the response endpoint, we found Ro 31-1215 and Ro 31-1741 to be 2-3 x and 4-7 x more potent then ADM, whilst Ro 31-2035 was 3-4 x less potent. For continuous drug exposure and suppression of population growth as the endpoint, the potency of Ro 31-1741 was similar to that of ADM, whereas that of Ro 31-1215 was 1.5-2 x higher and that of Ro 31-2035 was 10-20 x lower. The potency ratios for continuous drug exposure of a human small cell lung cancer line were similar to those for continuous exposure of EMT6. Variants of the two cell lines selected for resistance to ADM were also studied. These variants also showed considerable resistance to Ro 31-1741 and Ro 31-2035 but much less resistance to Ro 31-1215 (a 9-methyl derivative). A variant of EMT6 made resistant to Ro 31-1215 by continuous growth in this drug was more resistant to ADM than it was to Ro 31-1215. Human cells resistant to ADM contained 6 x less ADM after 24 h exposure than did the parent line, whereas the ratio of drug content for Ro 31-1215 was only 2.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baillie-Johnson H., Twentyman P. R., Fox N. E., Walls G. A., Workman P., Watson J. V., Johnson N., Reeve J. G., Bleehen N. M. Establishment and characterisation of cell lines from patients with lung cancer (predominantly small cell carcinoma). Br J Cancer. 1985 Oct;52(4):495–504. doi: 10.1038/bjc.1985.220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Davis H. L., Davis T. E. Daunorubicin and adriamycin in cancer treatment: an analysis of their roles and limitations. Cancer Treat Rep. 1979 May;63(5):809–815. [PubMed] [Google Scholar]
  3. Giavazzi R., Scholar E., Hart I. R. Isolation and preliminary characterization of an Adriamycin-resistant murine fibrosarcoma cell line. Cancer Res. 1983 May;43(5):2216–2222. [PubMed] [Google Scholar]
  4. Hill B. T., Dennis L. Y., Li X. T., Whelan R. D. Identification of anthracycline analogues with enhanced cytotoxicity and lack of cross-resistance to adriamycin using a series of mammalian cell lines in vitro. Cancer Chemother Pharmacol. 1985;14(3):194–201. doi: 10.1007/BF00258115. [DOI] [PubMed] [Google Scholar]
  5. Hubbard S. M., Barkes P., Young R. C. Adriamycin therapy for advanced ovarian carcinoma recurrent after chemotherapy. Cancer Treat Rep. 1978 Sep;62(9):1375–1377. [PubMed] [Google Scholar]
  6. Kaye S., Merry S. Tumour cell resistance to anthracyclines--a review. Cancer Chemother Pharmacol. 1985;14(2):96–103. doi: 10.1007/BF00434344. [DOI] [PubMed] [Google Scholar]
  7. Robert J., Illiadis A., Hoerni B., Cano J. P., Durand M., Lagarde C. Pharmacokinetics of adriamycin in patients with breast cancer: correlation between pharmacokinetic parameters and clinical short-term response. Eur J Cancer Clin Oncol. 1982 Aug;18(8):739–745. doi: 10.1016/0277-5379(82)90072-4. [DOI] [PubMed] [Google Scholar]
  8. Schabel F. M., Jr, Skipper H. E., Trader M. W., Laster W. R., Jr, Griswold D. P., Jr, Corbett T. H. Establishment of cross-resistance profiles for new agents. Cancer Treat Rep. 1983 Oct;67(10):905–922. [PubMed] [Google Scholar]
  9. Schwartz H. S. A fluorometric assay for daunomycin and adriamycin in animal tissues. Biochem Med. 1973 Jun;7(3):396–404. doi: 10.1016/0006-2944(73)90060-4. [DOI] [PubMed] [Google Scholar]
  10. Skovsgaard T., Danø K., Nissen N. I. Chemosensitizers counteracting acquired resistance to anthracyclines and vinca alkaloids in vivo. A new treatment principle. Cancer Treat Rev. 1984 Mar;11 (Suppl A):63–72. doi: 10.1016/0305-7372(84)90044-6. [DOI] [PubMed] [Google Scholar]
  11. Tsuruo T., Iida H., Tsukagoshi S., Sakurai Y. Potentiation of vincristine and Adriamycin effects in human hemopoietic tumor cell lines by calcium antagonists and calmodulin inhibitors. Cancer Res. 1983 May;43(5):2267–2272. [PubMed] [Google Scholar]
  12. Zenebergh A., Baurain R., Trouet A. Cellular pharmacokinetics of aclacinomycin A in cultured L1210 cells. Comparison with daunorubicin and doxorubicin. Cancer Chemother Pharmacol. 1982;8(2):243–249. doi: 10.1007/BF00255491. [DOI] [PubMed] [Google Scholar]

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