Cyclosporin A and FK506 reverse anthracycline resistance by altering the cell cycle

M. Yamamoto, H. Baba, T. Kusumoto, Y. Sakaguchi, Yoshihiko Maehara, M. Kuwano, K. Sugimachi

Research output: Contribution to journalArticle

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Abstract

We investigated the effect of cyclosporin A (CsA) or FK506 on the cytotoxicity of anthracyclines against a human laryngeal cancer cell line, KB cells, and a multidrug resistance cell line, VJ-300 cells. CsA and FK506 enhanced the cytotoxicity of anthracyclines, especially in the VJ-300 cells. The intracellular concentrations of epirubicin (EPIR), daunomycin (DM), adriamycin (ADM) and THP-adriamycin (THP) were increased by the addition of CsA or FK506 in VJ-300, but not in KB cells. The intracellular accumulation of EPIR was most increased when CsA or FK506 was concomitantly administered with the drug. We also asked whether CsA or FK506 might influence the cycle of KB or VJ-300 cells. The population of cells in each phase of the cell cycle was little changed in both KB and VJ-300 cells when 0.3 μM ADM was administered for 24 h. Both CsA and FK506 significantly increased the ADM-induced accumulation of VJ-300 cells in G2M phase, in comparison with findings with KB cells. Thus, the reversal of MDR by CsA or FK506 is related to increased intracellular concentrations of cytotoxic drugs and, as a result, the increased G2M accumulates in MDR cells. Among of anthracyclines, EPIR was most effective when concomitantly combined with CsA or FK506 in VJ-300 cells.

Original languageEnglish
Pages (from-to)570-577
Number of pages8
JournalAnti-cancer drugs
Volume6
Issue number4
DOIs
Publication statusPublished - Jan 1 1995

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Anthracyclines
Tacrolimus
Cyclosporine
Cell Cycle
KB Cells
Epirubicin
Doxorubicin
Cell Line
Daunorubicin
Laryngeal Neoplasms
Multiple Drug Resistance
Pharmaceutical Preparations
Population

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research

Cite this

Yamamoto, M., Baba, H., Kusumoto, T., Sakaguchi, Y., Maehara, Y., Kuwano, M., & Sugimachi, K. (1995). Cyclosporin A and FK506 reverse anthracycline resistance by altering the cell cycle. Anti-cancer drugs, 6(4), 570-577. https://doi.org/10.1097/00001813-199508000-00010

Cyclosporin A and FK506 reverse anthracycline resistance by altering the cell cycle. / Yamamoto, M.; Baba, H.; Kusumoto, T.; Sakaguchi, Y.; Maehara, Yoshihiko; Kuwano, M.; Sugimachi, K.

In: Anti-cancer drugs, Vol. 6, No. 4, 01.01.1995, p. 570-577.

Research output: Contribution to journalArticle

Yamamoto, M, Baba, H, Kusumoto, T, Sakaguchi, Y, Maehara, Y, Kuwano, M & Sugimachi, K 1995, 'Cyclosporin A and FK506 reverse anthracycline resistance by altering the cell cycle', Anti-cancer drugs, vol. 6, no. 4, pp. 570-577. https://doi.org/10.1097/00001813-199508000-00010
Yamamoto M, Baba H, Kusumoto T, Sakaguchi Y, Maehara Y, Kuwano M et al. Cyclosporin A and FK506 reverse anthracycline resistance by altering the cell cycle. Anti-cancer drugs. 1995 Jan 1;6(4):570-577. https://doi.org/10.1097/00001813-199508000-00010
Yamamoto, M. ; Baba, H. ; Kusumoto, T. ; Sakaguchi, Y. ; Maehara, Yoshihiko ; Kuwano, M. ; Sugimachi, K. / Cyclosporin A and FK506 reverse anthracycline resistance by altering the cell cycle. In: Anti-cancer drugs. 1995 ; Vol. 6, No. 4. pp. 570-577.
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