Skip to main content
Log in

Decreased retention of vinca alkaloids in chronic lymphatic leukemia cells from refractory patients

  • Original Articles
  • Vinca Alkaloids, Leukemic Cells
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Summary

Uptake and retention of vincristine (VCR), vinblastine (VB), and vindesine (VD) in isolated mononuclear cells from six healthy donors and in leukemic cells from 12 patients with chronic lymphatic leukemia (CLL) were studied: Three patients responded to VCR-containing regimens, whereas 4 patients were or became refractory and five patients did not receive VCR.

Incubation of leukemic or normal cells with 1 μg/ml vinca alkaloid for 1–24 h showed a steady state level after 1–2 h. Normal cells both took up and retained significantly more drug than those from patients, both responding and refractory.

Cells from VCR-refractory patients had a significantly (P<0.01) lower drug retention than those from patients responding to or not receiving VCR. In contrast, the difference in uptake was not statistically significant.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bleyer WA, Frisby SA, Olivero VT (1975) Uptake and binding of vincristine by murine leukemia cells. Biochem Pharmacol 24:633

    Google Scholar 

  2. Carter SK, Livingston RB (1976) Plant products in cancer chemotherapy. Cancer Treat Rep 60:1141

    Google Scholar 

  3. Csuka O, Sugar J, Palyi I, Somfai-Relle S (1980) The mode of action of vinca alkaloids. Oncology [Suppl 1]37:83

    Google Scholar 

  4. Danks MK, Beck WT (1983) Studies of resistance and crossresistance to vincristine, VM-26 and VP-16-213 in human leukemic cells. Proc Am Assoc Cancer Res p 282

  5. Dano K (1976) Cross-resistance between anthracyclines and vinca alkaloids: development of resistance to vincristine and vinblastine. Acta Pathol Microbiol Scand [A] [Suppl]256:39

    Google Scholar 

  6. Ferguson P, Phillips R, Selner M, Cass C (1983) Differential activity of vinca alkaloids against cultured cells. Proc Am Assoc Cancer Res p 286

  7. Hill BT, Whelan RD (1982) Establishment of vincristineresistant and vindesine-resistant lines of murine lymphoblasts in vitro and characterization of their patterns of cross-resistance and drug sensitivities. Cancer Chemother Pharmacol 8: 163

    Google Scholar 

  8. Inaba M, Fujikura R, Sakurai Y (1981a) Active efflux common to vincristine and daunorbicin in vincristine-resistant P3888 leukemia. Biochem Pharmacol 30:1863

    Google Scholar 

  9. Inaba M, Fujikura R, Tsukagoshi S, Sakurai Y (1981b) Restored in vitro sensitivity of adriamycinand vincristine-resistant P388 leukemia with reserpine. Biochem Pharmacol 30: 2191

    Google Scholar 

  10. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265

    CAS  PubMed  Google Scholar 

  11. Mathé G, Misset JL, De Vassal F, Gouveia J, Haya M, Machover D, Belpomme D, Pico JL, Schwarzenberg L, Ribaud P, Musset M, Jasmin CI, De Luca L (1978) Phase II clinical trial with vindesine for remission induction induction in acute leukemia, blastic crisis of chronic myeloid leukemia, lymphosarcoma, and Hodgkin's disease: Absence of cross resistance with vincristine. Cancer Treat Rep 62:805

    Google Scholar 

  12. Meyers MB, Kreis W, Degnan TJ, Biedler JL (1983) Mechanisms of resistance to vincristine in Chinese hamster lung cells. Proc Am Assoc Cancer Res p 42.

  13. Skovsgaard T (1978) Mechanism of cross-resistance between vincristine and daunorubicin in Ehrlich ascites tumor cells. Cancer Res 38:4722

    Google Scholar 

  14. Tapiero H, Fourcade A, Goldschmidt E, Zwingelstein G (1983) Mechanisms of resistance to anthracyclines. Current drugs and methods of cancer treatment. Mathé G, Mihich E, Reizenstein P (eds), Masson Publishing USA Inc. p 181

  15. Tsuruo T, Iida H, Tsukagoshi S, Sakurai Y (1981) Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res 41:1967

    CAS  PubMed  Google Scholar 

  16. Tsuruo T, Iida H, Tsukagoshi S, Sakurai Y (1983) Circumvention of vincristine and adriamycin resistance in vitro and in vivo by calcium influx blockers. Proc Am Assoc Cancer Res p 279

  17. Wilkoff LJ, Dulmadge EA (1981) Cultured leukemia P 388 cells resistant to vincristine (P 388/VCR): cross resistance to vinblastine (NSC 49842), vindesine (NSC 245467) and bis (N-ethylidene vindesine) disulfide, disulfate (NSC 277096). Proc Am Assoc Cancer Res p 239

  18. Yanovich S, Taub RN (1983) Differences in daunomycin uptake and retention in sensitive (s) and resistant (r) murine leukemia cells as determined by digitized video fluorescence microscopy (OVFM): Identification of uptake heterogeneity. Proc Am Assoc Cancer Res p 258

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by the Swedish Cancer Society and the Swedish Medical Research Council

Visiting scientist on leave from Dept of Internal Medicine, Hacettepe University, Ankara, Turkey

Rights and permissions

Reprints and permissions

About this article

Cite this article

Beksac, M., Peterson, C. & Reizenstein, P. Decreased retention of vinca alkaloids in chronic lymphatic leukemia cells from refractory patients. Cancer Chemother. Pharmacol. 15, 72–75 (1985). https://doi.org/10.1007/BF00257299

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00257299

Keywords

Navigation