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. 1994 Mar;69(3):497–501. doi: 10.1038/bjc.1994.90

Effects of the ACTH(4-9) analogue, ORG 2766, on vincristine cytotoxicity in two human lymphoma cell lines, U937 and U715.

B Kiburg 1, A A van de Loosdrecht 1, K M Schweitzer 1, G J Ossenkoppele 1, L J Müller 1, J J Heimans 1, P C Huijgens 1
PMCID: PMC1968834  PMID: 8123480

Abstract

The use of cytotoxic drug vincristine (VCR) is limited by the occurrence of peripheral neuropathy. A neurotrophic ACTH(4-9) analogue, ORG 2766, is being studied for its protective effect. Possible modulatory effects of ORG 2766 on tumour cell growth and interference with the cytotoxic efficacy of VCR were studied in two human lymphoma cell lines, U937 and U715. The effects of ORG 2766 on cell growth and survival and on VCR-mediated cytotoxicity were investigated using two MTT-based assays to study direct cytotoxic effects and to assess residual growth after pretreatment. Treatment with ORG 2766 alone had no effect on cell growth and survival. Neither did this drug affect VCR cytotoxicity. However, after 96 h pretreatment with ORG 2766 and a culture period of 7 days, a reduction in residual growth and a potentiation of VCR-induced inhibition of growth capacity was observed in U715 cells, and to some extent also in U937 cells. It is concluded that ORG 2766 has no stimulatory effects on tumour growth and does not negatively interfere with VCR-mediated cytotoxicity. Rather it enhances the cytostatic effect of VCR. It is suggested that ORG 2766 can safely be used in clinical trials investigating the ability of ORG 2766 to counteract VCR-induced neurotoxicity.

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Selected References

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  1. Alley M. C., Scudiero D. A., Monks A., Hursey M. L., Czerwinski M. J., Fine D. L., Abbott B. J., Mayo J. G., Shoemaker R. H., Boyd M. R. Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res. 1988 Feb 1;48(3):589–601. [PubMed] [Google Scholar]
  2. Bender R. A., Castle M. C., Margileth D. A., Oliverio V. T. The pharmacokinetics of [3H]-vincristine in man. Clin Pharmacol Ther. 1977 Oct;22(4):430–435. doi: 10.1002/cpt1977224430. [DOI] [PubMed] [Google Scholar]
  3. Bunt A. H. Paracrystalline inclusions in optic nerve terminals following intraocular injection of vinblastine. Brain Res. 1973 Apr 13;53(1):29–39. doi: 10.1016/0006-8993(73)90764-6. [DOI] [PubMed] [Google Scholar]
  4. Carlsson J., Nilsson K., Westermark B., Pontén J., Sundström C., Larsson E., Bergh J., Påhlman S., Busch C., Collins V. P. Formation and growth of multicellular spheroids of human origin. Int J Cancer. 1983 May 15;31(5):523–533. doi: 10.1002/ijc.2910310502. [DOI] [PubMed] [Google Scholar]
  5. De Koning P., Gispen W. H. Org.2766 improves functional and electrophysiological aspects of regenerating sciatic nerve in the rat. Peptides. 1987 May-Jun;8(3):415–422. doi: 10.1016/0196-9781(87)90003-9. [DOI] [PubMed] [Google Scholar]
  6. Donoso J. A., Green L. S., Heller-Bettinger I. E., Samson F. E. Action of the vinca alkaloids vincristine, vinblastine, and desacetyl vinblastine amide on axonal fibrillar organelles in vitro. Cancer Res. 1977 May;37(5):1401–1407. [PubMed] [Google Scholar]
  7. Ferguson P. J., Phillips J. R., Selner M., Cass C. E. Differential activity of vincristine and vinblastine against cultured cells. Cancer Res. 1984 Aug;44(8):3307–3312. [PubMed] [Google Scholar]
  8. Gerritsen van der Hoop R., de Koning P., Boven E., Neijt J. P., Jennekens F. G., Gispen W. H. Efficacy of the neuropeptide ORG.2766 in the prevention and treatment of cisplatin-induced neurotoxicity in rats. Eur J Cancer Clin Oncol. 1988 Apr;24(4):637–642. doi: 10.1016/0277-5379(88)90293-3. [DOI] [PubMed] [Google Scholar]
  9. Gout P. W., Noble R. L., Bruchovsky N., Beer C. T. Vinblastine and vincristine--growth-inhibitory effects correlate with their retention by cultured Nb 2 node lymphoma cells. Int J Cancer. 1984 Aug 15;34(2):245–248. doi: 10.1002/ijc.2910340216. [DOI] [PubMed] [Google Scholar]
  10. Jackson D. V., Jr, Bender R. A. Cytotoxic thresholds of vincristine in a murine and a human leukemia cell line in vitro. Cancer Res. 1979 Nov;39(11):4346–4349. [PubMed] [Google Scholar]
  11. Jackson D. V., Jr, McMahan R. A., Pope E. K., Case L. D., Cooper M. R., Kaplon M. K., Richards F., 2nd, Stuart J. J., White D. R., Zekan P. J. Clinical trial of folinic acid to reduce vincristine neurotoxicity. Cancer Chemother Pharmacol. 1986;17(3):281–284. doi: 10.1007/BF00256700. [DOI] [PubMed] [Google Scholar]
  12. Jackson D. V., Jr, Pope E. K., McMahan R. A., Cooper M. R., Atkins J. N., Callahan R. D., Paschold E. H., Grimm R. A., Hopkins J. O., Muss H. B. Clinical trial of pyridoxine to reduce vincristine neurotoxicity. J Neurooncol. 1986;4(1):37–41. doi: 10.1007/BF02158000. [DOI] [PubMed] [Google Scholar]
  13. Jackson D. V., Jr, Sethi V. S., Spurr C. L., McWhorter J. M. Pharmacokinetics of vincristine in the cerebrospinal fluid of humans. Cancer Res. 1981 Apr;41(4):1466–1468. [PubMed] [Google Scholar]
  14. Jackson D. V., Wells H. B., Atkins J. N., Zekan P. J., White D. R., Richards F., 2nd, Cruz J. M., Muss H. B. Amelioration of vincristine neurotoxicity by glutamic acid. Am J Med. 1988 Jun;84(6):1016–1022. doi: 10.1016/0002-9343(88)90306-3. [DOI] [PubMed] [Google Scholar]
  15. Legha S. S. Vincristine neurotoxicity. Pathophysiology and management. Med Toxicol. 1986 Nov-Dec;1(6):421–427. doi: 10.1007/BF03259853. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Murry R., McLane J. A., Gruener G. Effects of ORG 2766, a neurotrophic ACTH4-9 analogue, in neuroblastoma cells. Ann N Y Acad Sci. 1993 May 28;679:270–275. doi: 10.1111/j.1749-6632.1993.tb18307.x. [DOI] [PubMed] [Google Scholar]
  18. Müller L. J., Moorer-van Delft C. M., Boer H. H. The ACTH/MSH(4-9) analogue ORG 2766 stimulates microtubule formation in axons of central neurons of the snail Lymnaea stagnalis. Peptides. 1992 Jul-Aug;13(4):769–774. doi: 10.1016/0196-9781(92)90185-6. [DOI] [PubMed] [Google Scholar]
  19. Müller L. J., Moorer-van Delft C. M., Roubos E. W. Snail neurons as a possible model for testing neurotoxic side effects of antitumor agents: paracrystal formation by Vinca alkaloids. Cancer Res. 1988 Dec 15;48(24 Pt 1):7184–7188. [PubMed] [Google Scholar]
  20. Nilsson K., Sundström C. Establishment and characteristics of two unique cell lines from patients with lymphosarcoma. Int J Cancer. 1974 Jun 15;13(6):808–823. doi: 10.1002/ijc.2910130609. [DOI] [PubMed] [Google Scholar]
  21. Rosenthal S., Kaufman S. Vincristine neurotoxicity. Ann Intern Med. 1974 Jun;80(6):733–737. doi: 10.7326/0003-4819-80-6-733. [DOI] [PubMed] [Google Scholar]
  22. Schweitzer C. M., van de Loosdrecht A. A., Jonkhoff A. R., Ossenkoppele G. J., Huijgens P. C., Dräger A. M., Broekhoven M. G., Langenhuijsen M. M. Spectrophotometric determination of clonogenic capacity of leukemic cells in a semisolid microtiter culture system. Exp Hematol. 1993 Apr;21(4):573–578. [PubMed] [Google Scholar]
  23. Takanari H., Yosida T., Morita J., Izutsu K., Ito T. Instability of pleomorphic tubulin paracrystals artificially induced by Vinca alkaloids in tissue-cultured cells. Biol Cell. 1990;70(1-2):83–90. doi: 10.1016/0248-4900(90)90363-8. [DOI] [PubMed] [Google Scholar]
  24. Yamashita Y., Nara N., Aoki N. The effects of vincristine and doxorubicin on the clonogenic cells of a human lung cancer cell line in methylcellulose and suspension culture. Jpn J Cancer Res. 1989 Mar;80(3):277–282. doi: 10.1111/j.1349-7006.1989.tb02305.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. de Koning P., Neijt J. P., Jennekens F. G., Gispen W. H. Org.2766 protects from cisplatin-induced neurotoxicity in rats. Exp Neurol. 1987 Sep;97(3):746–750. doi: 10.1016/0014-4886(87)90132-4. [DOI] [PubMed] [Google Scholar]
  26. van Kooten B., van Diemen H. A., Groenhout K. M., Huijgens P. C., Ossenkoppele G. J., Nauta J. J., Heimans J. J. A pilot study on the influence of a corticotropin (4-9) analogue on Vinca alkaloid-induced neuropathy. Arch Neurol. 1992 Oct;49(10):1027–1031. doi: 10.1001/archneur.1992.00530340043016. [DOI] [PubMed] [Google Scholar]
  27. van Tellingen O., Sips J. H., Beijnen J. H., Bult A., Nooijen W. J. Pharmacology, bio-analysis and pharmacokinetics of the vinca alkaloids and semi-synthetic derivatives (review). Anticancer Res. 1992 Sep-Oct;12(5):1699–1715. [PubMed] [Google Scholar]
  28. van de Loosdrecht A. A., Nennie E., Ossenkoppele G. J., Beelen R. H., Langenhuijsen M. M. Cell mediated cytotoxicity against U 937 cells by human monocytes and macrophages in a modified colorimetric MTT assay. A methodological study. J Immunol Methods. 1991 Jul 26;141(1):15–22. doi: 10.1016/0022-1759(91)90205-t. [DOI] [PubMed] [Google Scholar]
  29. van der Hoop R. G., Brakkee J. H., Kapelle A., Samson M., de Koning P., Gispen W. H. A new approach for the evaluation of recovery after peripheral nerve damage. J Neurosci Methods. 1988 Dec;26(2):111–116. doi: 10.1016/0165-0270(88)90159-8. [DOI] [PubMed] [Google Scholar]
  30. van der Hoop R. G., Vecht C. J., van der Burg M. E., Elderson A., Boogerd W., Heimans J. J., Vries E. P., van Houwelingen J. C., Jennekens F. G., Gispen W. H. Prevention of cisplatin neurotoxicity with an ACTH(4-9) analogue in patients with ovarian cancer. N Engl J Med. 1990 Jan 11;322(2):89–94. doi: 10.1056/NEJM199001113220204. [DOI] [PubMed] [Google Scholar]

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