FTY720, a novel immunosuppressive agent, induces apoptosis in human glioma cells

Y. Sonoda, D. Yamamoto, S. Sakurai, M. Hasegawa, Eriko Yokota, T. Momoi, T. Kasahara

Research output: Contribution to journalArticle

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Abstract

FTY720, a metabolite from Isaria sinclairii, has been developed to be a potent immunosuppressive drug with induction of apoptosis in T cells and several cell lines. We investigated whether FTY720 induces apoptosis in human glioma cell lines, since they are relatively resistant to multiple apoptotic stimuli. In human glioma cells including T98G, FTY720 induced apoptosis with ED50 between 1 to 10 μg/ml, while etoposide did not induce apoptosis at the same doses. Among the caspase family proteases, mainly caspase-6 was activated during the apoptosis by FTY720 but not etoposide. In addition, FTY720 caused tyrosine dephosphorylation of FAK and did not activate a FAK-PI3-kinase survival pathway. This was confirmed also by the observation that orthovanadate prevented FTY720-induced dephosphorylation of FAK and inhibited FTY720-induced cell death. We assumed that FTY720 induced FAK dephosphorylation and cut off the FAK-PI3-kinase pathway resulting in the induction of apoptosis via caspase-6 activation in these glioma cells.

Original languageEnglish
Pages (from-to)282-288
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume281
Issue number2
DOIs
Publication statusPublished - 2001

Fingerprint

Immunosuppressive Agents
Glioma
Apoptosis
Caspase 6
Etoposide
Phosphatidylinositol 3-Kinases
Cells
Cell Line
Vanadates
T-cells
Fingolimod Hydrochloride
Cell death
Caspases
Metabolites
Tyrosine
Peptide Hydrolases
Cell Death
Chemical activation
T-Lymphocytes
Survival

Keywords

  • Apoptosis
  • Caspase-6
  • Etoposide
  • FAK
  • FTY720
  • Glioma
  • PI3-kinase
  • Survival pathway

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

FTY720, a novel immunosuppressive agent, induces apoptosis in human glioma cells. / Sonoda, Y.; Yamamoto, D.; Sakurai, S.; Hasegawa, M.; Yokota, Eriko; Momoi, T.; Kasahara, T.

In: Biochemical and Biophysical Research Communications, Vol. 281, No. 2, 2001, p. 282-288.

Research output: Contribution to journalArticle

Sonoda, Y. ; Yamamoto, D. ; Sakurai, S. ; Hasegawa, M. ; Yokota, Eriko ; Momoi, T. ; Kasahara, T. / FTY720, a novel immunosuppressive agent, induces apoptosis in human glioma cells. In: Biochemical and Biophysical Research Communications. 2001 ; Vol. 281, No. 2. pp. 282-288.
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AU - Yamamoto, D.

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AU - Hasegawa, M.

AU - Yokota, Eriko

AU - Momoi, T.

AU - Kasahara, T.

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