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[Search for new MDR modifier possessing taxane skeleton]

J Kobayashi1

  • 1Faculty of Pharmaceutical Sciences, Hokkaido University.

Nihon Rinsho. Japanese Journal of Clinical Medicine
|May 1, 1997
PubMed
Summary
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New taxoids from Japanese yew show potential in cancer treatment. Some compounds inhibit microtubule depolymerization and overcome multidrug resistance (MDR) in tumor cells by affecting P-glycoprotein.

Area of Science:

  • Natural Product Chemistry
  • Pharmacology
  • Oncology

Background:

  • Taxus cuspidata (Japanese yew) is a source of taxoids, including paclitaxel (Taxol).
  • Multidrug resistance (MDR) is a major challenge in cancer chemotherapy, often mediated by P-glycoprotein.
  • Taxol and its analogs are effective chemotherapeutics but can be subject to MDR.

Purpose of the Study:

  • To isolate and characterize new taxoids from Taxus cuspidata.
  • To evaluate the effects of novel taxoids on microtubule stability.
  • To investigate the potential of these compounds in overcoming MDR in tumor cells.

Main Methods:

  • Isolation and structural elucidation of taxoids from Taxus cuspidata stems and leaves.
  • Assessment of CaCl2-induced microtubule depolymerization.

Related Experiment Videos

  • Measurement of vincristine accumulation in multidrug-resistant tumor cells.
  • Inhibition assays for azidopine binding to P-glycoprotein.

    • Main Results:

    • Two novel non-taxol-type taxoids reduced microtubule depolymerization.
    • Seven non-taxol-type taxoids enhanced vincristine accumulation in MDR cells, comparable to verapamil.
    • These compounds competitively inhibited azidopine binding to P-glycoprotein, suggesting interaction with this efflux pump.

    Conclusions:

    • Non-taxol-type taxoids from Taxus cuspidata possess distinct biological activities.
    • These compounds demonstrate potential for overcoming P-glycoprotein-mediated multidrug resistance.
    • Further investigation of these taxoids could lead to novel therapeutic strategies for resistant cancers.