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Collateral sensitivity between methylene dimethane sulfonate and halogenated methotrexate derivatives in the Yoshida

B W Fox

    Journal of the National Cancer Institute
    |April 1, 1977
    PubMed

    Insights

    Methylene dimethane sulfonate-resistant Yoshida lymphosarcoma cells showed collateral sensitivity to certain halogenated methotrexate analogs, but not to methotrexate itself. Tumor subpopulation changes may influence this drug sensitivity.

    Area of Science:

    • Oncology
    • Pharmacology
    • Cell Biology

    Background:

    • Drug resistance is a major challenge in cancer therapy.
    • Understanding collateral sensitivity can reveal new therapeutic strategies.

    Purpose of the Study:

    • To investigate collateral sensitivity in methylene dimethane sulfonate-resistant Yoshida lymphosarcoma (YMDR8) cells.
    • To examine cross-resistance patterns with methotrexate and its analogs.

    Main Methods:

    • Established methylene dimethane sulfonate-resistant cell lines (YMDR8, YMDR7, YMDR9).
    • Assessed sensitivity to methotrexate and halogenated methotrexate analogs in vitro and in vivo.
    • Analyzed tumor subpopulation changes.

    Main Results:

    • YMDR8 cells exhibited collateral sensitivity to 3'-bromomethotrexate, 3'-bromo-5'-chloromethotrexate, and 3',5'-dichloromethotrexate.
    • YMDR8 cells showed cross-resistance to methotrexate.
    • Other resistant lines (YMDR7, YMDR9) also showed collateral sensitivity to 3'-bromomethotrexate.

    Conclusions:

    • Drug-resistant cancer cell lines can display collateral sensitivity to specific chemotherapeutic agents.
    • Tumor subpopulation dynamics may play a role in the development of collateral sensitivity.
    • Halogenated methotrexates show potential as alternative treatments for resistant cancers.

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