Modulation of methotrexate resistance by genistein in murine leukemia L1210 cells.

  • Authors:
    • Y Xuan
    • M P Hacker
    • T R Tritton
    • A Bhushan
  • View Affiliations

  • Published online on: March 1, 1998     https://doi.org/10.3892/or.5.2.419
  • Pages: 419-440
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Abstract

We have previously shown that methotrexate (MTX) transport is impaired in murine L1210 cells selected for cisplatin (DDP) resistance (L1210/DDP) and that the decreased MTX uptake may be due to an altered 66 kDa membrane protein. We have further hypothesized that tyrosine phosphorylation is necessary for the function of this protein. To determine the importance of tyrosine phosphorylation we studied the effect of genistein, a tyrosine kinase inhibitor, on methotrexate sensitivity, uptake and tyrosine phosphorylation of the 66 kDa protein in L1210/0 cells. After 5 h of treatment with 50 microM genistein, methotrexate uptake was decreased by nearly 50% and the cells were protected from methotrexate cytotoxicity. Immunoblotting of whole cell lysates with a phosphotyrosine monoclonal antibody demonstrated that genistein treatment decreased phosphorylation of the 66 kDa membrane protein. We concluded that phosphorylation of a 66 kDa protein may be critical for methotrexate transport and that genistein protects L1210/0 cells from methotrexate toxicity.

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March 1998
Volume 5 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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APA
Xuan, Y., Hacker, M., Tritton, T., & Bhushan, A. (1998). Modulation of methotrexate resistance by genistein in murine leukemia L1210 cells.. Oncology Reports, 5, 419-440. https://doi.org/10.3892/or.5.2.419
MLA
Xuan, Y., Hacker, M., Tritton, T., Bhushan, A."Modulation of methotrexate resistance by genistein in murine leukemia L1210 cells.". Oncology Reports 5.2 (1998): 419-440.
Chicago
Xuan, Y., Hacker, M., Tritton, T., Bhushan, A."Modulation of methotrexate resistance by genistein in murine leukemia L1210 cells.". Oncology Reports 5, no. 2 (1998): 419-440. https://doi.org/10.3892/or.5.2.419