Vitamin A Does Not Enhance the Antileukemic Effect of Vincristine, Daunorubicin, and 6-Thioguanine in Acute Lymphoblastic Leukemia Cells

  • R. Pieters
  • D. R. Huismans
  • A. H. Loonen
  • K. Hählen
  • A. J. P. Veerman
Conference paper
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 36)


Retinoids, analogs of vitamin A, have been shown to inhibit growth and induce maturation in a large variety of tumor types. The results of many studies on this subject have been reviewed extensively by Lippman et al. [1,2]. In these reviews it was suggested that retinoids have synergistic activity in combination with cytostatic drugs. The data to support this suggestion are however scarce and all reports on these studies dealt with cell lines or animal models [3–7]. No studies using cells derived directly from patients have been reported as far as we know. We recently adapted the MTT assay to assess in vitro cytotoxic effects of chemotherapeutic drugs upon cells derived from leukemic patients [8,9]. With this assay combinations of resistance modifying agents with anticancer drugs were tested using cells from leukemic patients [10]. In the present study we evaluated whether vitamin A was capable of potentiating the cytotoxic effect of anticancer drugs against tumor cells obtained from patients with acute lymphoblastic leukemia (ALL).


Acute Lymphoblastic Leukemia Childhood Leukemia Cytostatic Drug Acute Lymphoblastic Leukemia Cell Multidrug Resistance Phenotype 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Lippman SM, Kessler IF, Meyskens FL (1987) Retinoids as preventive and therapeutic anticancer agents (part I). Cancer Treat Rep 71: 391PubMedGoogle Scholar
  2. 2.
    Lippman SM, Kessler IF, Meyskens FL (1987) Retinoids as preventive and therapeutic anticancer agents (part II). Cancer Treat Rep 71: 493PubMedGoogle Scholar
  3. 3.
    Akiyama S, Masuda A, Tabuki T, Kuwano M, Komiyama S (1981) Enhancement of the antitumor effect of 6-mercaptopurine by vitamin A. Jpn J Cancer Res 72: 742Google Scholar
  4. 4.
    Nakagawa M, Yamaguchi T, Veda H, Shiraishi N, Komiyama S, Akiyama S, Ogata J, Kuwano M (1985) Potentiation by vitamin A of the action of anticancer agents against murine tumors. Jpn J Cancer Res 76: 887PubMedGoogle Scholar
  5. 5.
    Nogae I, Kikuchi J, Yamaguchi T, Shiraishi N, Kuwano M (1987) Potentiation of vincristine by vitamin A against drug-resistant mouse leukaemia cells. Br J Cancer 56: 267PubMedCrossRefGoogle Scholar
  6. 6.
    Bregman MD, Peters E, Sander D, Meyskens FL (1983) Dexamethasone, prostaglandin A, and retinoic acid modulation of murine and human melanoma cells grown in soft agar. J Natl Cancer Inst 71: 927PubMedGoogle Scholar
  7. 7.
    Gaukroger JM, Wilson L, MacKie R (1985) Cytotoxicity of etretinate and vindesine. Br J Cancer 52: 369PubMedCrossRefGoogle Scholar
  8. 8.
    Pieters R, Huismans DR, Leyva A, Veerman AJP (1988) Adaptation of a rapid tetrazolium based (MTT-) assay for chemosensitivity testing in childhood leukemia. Cancer Lett 41: 323PubMedCrossRefGoogle Scholar
  9. 9.
    Pieters R, Huismans DR, Leyva A, Veerman AJP (1989) Comparison of the rapid automated MTT-assay with a dye exclusion assay for chemosensitivity testing in childhood leukemia. Br J Cancer 59: 217PubMedCrossRefGoogle Scholar
  10. 10.
    Twentyman PR, Fox NE, Rees JKH (1989) Chemosensitivity testing of fresh leukaemia cells using the MTT colorimetric assay. Br J Haematol 71: 19PubMedCrossRefGoogle Scholar
  11. 11.
    Pieters R, Loonen AH, Huismans DR, Broekema GJ, Dirven MWJ, Heyenbrok MW, Hählen K, Veerman AJP (1990) In vitro sensitivity of cells from children with leukemia using the MTT assay with improved culture conditions. Blood 76: 2327PubMedGoogle Scholar
  12. 12.
    Pieters R, Hongo T, Loonen AH, Huismans DR, Broxterman HJ, Hählen K, Veerman AJP (1992) Non-p-glycoprotein mediated multiple drug resistance in children with relapsed acute lymphoblastic leukemia. Br J Cancer 65: 691PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • R. Pieters
    • 1
  • D. R. Huismans
    • 1
  • A. H. Loonen
    • 1
  • K. Hählen
    • 2
  • A. J. P. Veerman
    • 1
  1. 1.Department of PediatricsFree University HospitalAmsterdamThe Netherlands
  2. 2.Sophia’s Children Hospital, Subdivision Haemato/OncologyErasmus UniversityRotterdamThe Netherlands

Personalised recommendations