Bcl-2 inhibits calcineurin-mediated Fas ligand expression in antitumor drug-treated baby hamster kidney cells

Siro Simizu, Futoshi Shibasaki, Hiroyuki Osada

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


It is well known that human leukemia cells, such as HL-60 and U937 are sensitive to antitumor drugs, but human normal lung fibroblasts, such as WI-38 cells are resistant to the drugs. However, the mechanisms of the different responses to apoptosis in these cell lines remain unclear. We report here that an increase of Fas and Fas ligand (FasL) expression was required for antitumor drug-induced apoptosis in WI-38 and baby hamster kidney (BHK) cells, but not in HL-60 cells. Then, we used BHK cells transfected with the bcl-2 gene to investigate the involvement of complex formation of Bcl-2 and calcineurin. Calcineurin was imported to the nucleus in response to the drug treatment. Overexpression of Bcl-2 and cyclosporin A treatment inhibited the nuclear import and FasL expression, and as a result, both inhibited apoptosis. Although a caspase inhibitor, z-Asp-CH2-DCB, suppressed the drug-induced apoptosis, it failed to inhibit the drug-induced expression of Fas and FasL. These findings suggest that initially the Fas/FasL system is activated by calcineurin-dependent transcription followed by activation of the downstream caspase cascade resulting in antitumor drug-induced apoptosis in BHK cells, but not in HL-60 cells. Furthermore, Bcl-2 inhibits the nuclear import of calcineurin and suppresses calcineurin-mediated FasL expression during antitumor drug-induced apoptosis.

Original languageEnglish
Pages (from-to)706-714
Number of pages9
JournalJapanese Journal of Cancer Research
Issue number7
Publication statusPublished - 2000
Externally publishedYes


  • Bcl-2
  • Calcineurin
  • Fas
  • Pironetin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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