Cell-cycle-dependent pharmacology of methotrexate in HL-60

Atsushi Yamauchi, Takanobu Ichimiya, Kouichi Inoue, Yukie Taguchi, Naoya Matsunaga, Satoru Koyanagi, Tatsuo Fukagawa, Hironori Aramaki, Shun Higuchi, Shigehiro Ohdo

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14 Citations (Scopus)

Abstract

The role of the susceptibility of cells and the pharmacokinetics of MTX on the time-dependent change of methotrexate (MTX) pharmacologic action in HL-60 (human leukemia cell) was investigated from the viewpoints of the rhythm of DNA synthesis. The highest activity of MTX was observed at the time when DNA synthesis, dihydrofolate reductase (DHFR) activity, DHFR content, and DHFR mRNA content increased and the lowest activity was observed at the time when they decreased. There were significant time-dependent changes in MTX efflux. The result corresponded to the rhythm in MTX activity. The present study suggests that the time-dependent change of MTX activity is caused by a change in the sensitivity of cells and the pharmacokinetics of the drug. Therefore, the choice of dosing time associated with cell rhythmicity may help to achieve rational chronotherapeutics, increasing therapeutic effects.

Original languageEnglish
Pages (from-to)335-341
Number of pages7
JournalJournal of Pharmacological Sciences
Volume99
Issue number4
DOIs
Publication statusPublished - Dec 27 2005

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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    Yamauchi, A., Ichimiya, T., Inoue, K., Taguchi, Y., Matsunaga, N., Koyanagi, S., Fukagawa, T., Aramaki, H., Higuchi, S., & Ohdo, S. (2005). Cell-cycle-dependent pharmacology of methotrexate in HL-60. Journal of Pharmacological Sciences, 99(4), 335-341. https://doi.org/10.1254/jphs.FP0050761