Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1995 Feb;114(3):715–719. doi: 10.1111/j.1476-5381.1995.tb17197.x

Interaction between methotrexate and indomethacin on a human normal haemopoietic cell line.

S J Hollingsworth 1, N P Shankley 1, E M Anderson 1, A Bennett 1
PMCID: PMC1510021  PMID: 7735697

Abstract

1. The interaction between methotrexate and indomethacin has been examined, at a physiological folate concentration (20 nM), on a human normal lymphoblast-like cell line (RPMI 1788) in vitro. 2. Indomethacin (1 microgram ml-1) increased the reduction of lymphoblast growth caused by methotrexate (10-80 ng ml-1). 3. Indomethacin (0.1 and 1 microgram ml-1) potentiated the cytotoxicity of methotrexate (20 and 40 ng ml-1) after 4 days in culture. 4. Indomethacin (0.4 micrograms ml-1) reduced the accumulation of tritium in lymphoblasts incubated with [3H]-methotrexate after 30 min; therefore initial drug accumulation was not responsible for the potentiation seen after 4 days. 5. If indomethacin increases the killing of human cancer cells by methotrexate in vivo, with a smaller potentiation on lymphoblasts, this combination may be beneficial in treating human malignancy.

Full text

PDF
715

Selected References

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

  1. Bennett A., Gaffen J. D., Chambers E. Cyclo-oxygenase inhibitors and cell killing by cytotoxic drugs. Adv Prostaglandin Thromboxane Leukot Res. 1989;19:427–430. [PubMed] [Google Scholar]
  2. Bennett A., Gaffen J. D., Melhuish P. B., Stamford I. F. Studies on the mechanism by which indomethacin increases the anticancer effect of methotrexate. Br J Pharmacol. 1987 May;91(1):229–235. doi: 10.1111/j.1476-5381.1987.tb09003.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Daly H., Boyle J., Roberts C., Scott G. Interaction between methotrexate and non-steroidal anti-inflammatory drugs. Lancet. 1986 Mar 8;1(8480):557–557. doi: 10.1016/s0140-6736(86)90910-4. [DOI] [PubMed] [Google Scholar]
  4. Day R. O., Graham G. G., Champion G. D., Lee E. Anti-rheumatic drug interactions. Clin Rheum Dis. 1984 Aug;10(2):251–275. [PubMed] [Google Scholar]
  5. Dong H., Lee C. M., Huang W. L., Peng S. X. Cardiovascular effects of substituted tetrahydroisoquinolines in rats. Br J Pharmacol. 1992 Sep;107(1):262–268. doi: 10.1111/j.1476-5381.1992.tb14496.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ellison N. M., Servi R. J. Acute renal failure and death following sequential intermediate-dose methotrexate and 5-FU: a possible adverse effect due to concomitant indomethacin administration. Cancer Treat Rep. 1985 Mar;69(3):342–343. [PubMed] [Google Scholar]
  7. Gaffen J. D., Bennett A., Barer M. R. A new method for studying cell growth in suspension, and its use to show that indomethacin enhances cell killing by methotrexate. J Pharm Pharmacol. 1985 Apr;37(4):261–263. doi: 10.1111/j.2042-7158.1985.tb05056.x. [DOI] [PubMed] [Google Scholar]
  8. Henderson G. B., Zevely E. M., Huennekens F. M. Cyclic adenosine 3':5'-monophosphate and methotrexate transport in L1210 cells. Cancer Res. 1978 Mar;38(3):859–861. [PubMed] [Google Scholar]
  9. Hewitt H. B., Blake E. R., Walder A. S. A critique of the evidence for active host defence against cancer, based on personal studies of 27 murine tumours of spontaneous origin. Br J Cancer. 1976 Mar;33(3):241–259. doi: 10.1038/bjc.1976.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Huang C. C., Moore G. E. Chromosomes of 14 hematopoietic cell lines derived from peripheral blood of persons with and without chromosome anomalies. J Natl Cancer Inst. 1969 Nov;43(5):1119–1128. [PubMed] [Google Scholar]
  11. Jansen G., Westerhof G. R., Jarmuszewski M. J., Kathmann I., Rijksen G., Schornagel J. H. Methotrexate transport in variant human CCRF-CEM leukemia cells with elevated levels of the reduced folate carrier. Selective effect on carrier-mediated transport of physiological concentrations of reduced folates. J Biol Chem. 1990 Oct 25;265(30):18272–18277. [PubMed] [Google Scholar]
  12. Jurásková V. The cytotoxic effect of methotrexate as evaluated by colony-forming activity of hemopoietic and tumor cells. Neoplasma. 1988;35(5):583–589. [PubMed] [Google Scholar]
  13. Maiche A. G. Acute renal failure due to concomitant action of methotrexate and indomethacin. Lancet. 1986 Jun 14;1(8494):1390–1390. doi: 10.1016/s0140-6736(86)91706-x. [DOI] [PubMed] [Google Scholar]
  14. Nierenberg D. W. Competitive inhibition of methotrexate accumulation in rabbit kidney slices by nonsteroidal anti-inflammatory drugs. J Pharmacol Exp Ther. 1983 Jul;226(1):1–6. [PubMed] [Google Scholar]
  15. Schrøder H. Methotrexate kinetics in myeloid bone marrow cells and peripheral neutrophils. Cancer Chemother Pharmacol. 1987;19(1):42–46. doi: 10.1007/BF00296254. [DOI] [PubMed] [Google Scholar]
  16. Seideman P., Sollevi A., Fredholm B. B. Additive renal effects of indomethacin and dipyridamole in man. Br J Clin Pharmacol. 1987 Mar;23(3):323–330. doi: 10.1111/j.1365-2125.1987.tb03052.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Singh R. R., Malaviya A. N., Pandey J. N., Guleria J. S. Fatal interaction between methotrexate and naproxen. Lancet. 1986 Jun 14;1(8494):1390–1390. doi: 10.1016/s0140-6736(86)91707-1. [DOI] [PubMed] [Google Scholar]
  18. Sirotnak F. M. Obligate genetic expression in tumor cells of a fetal membrane property mediating "folate" transport: biological significance and implications for improved therapy of human cancer. Cancer Res. 1985 Sep;45(9):3992–4000. [PubMed] [Google Scholar]
  19. Thyss A., Milano G., Kubar J., Namer M., Schneider M. Clinical and pharmacokinetic evidence of a life-threatening interaction between methotrexate and ketoprofen. Lancet. 1986 Feb 1;1(8475):256–258. doi: 10.1016/s0140-6736(86)90786-5. [DOI] [PubMed] [Google Scholar]
  20. Von Hoff D. D., Penta J. S., Helman L. J., Slavik M. Incidence of drug-related deaths secondary to high-dose methotrexate and citrovorum factor administration. Cancer Treat Rep. 1977 Jul;61(4):745–748. [PubMed] [Google Scholar]
  21. Walder C. E., Thiemermann C., Vane J. R. NG-hydroxy-L-arginine prevents the haemodynamic effects of nitric oxide synthesis inhibition in the anaesthetized rat. Br J Pharmacol. 1992 Oct;107(2):476–480. doi: 10.1111/j.1476-5381.1992.tb12770.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Williams L. H., Udupa K. B., Lipschitz D. A. Long-term bone marrow culture as a model for host toxicity: the effect of methotrexate on hematopoiesis and adherent layer function. Exp Hematol. 1988 Jan;16(1):80–87. [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES