A novel immunosuppressive agent FTY720 induced Akt dephosphorylation in leukemia cells
Y Matsuoka, Y Nagahara, M Ikekita… - British journal of …, 2003 - Wiley Online Library
Y Matsuoka, Y Nagahara, M Ikekita, T Shinomiya
British journal of pharmacology, 2003•Wiley Online LibraryOur previous studies revealed that the immunosuppressive agent, FTY720, mainly induces
mitochondria‐involved apoptosis in some types of cancer cells, since Bcl‐2 overexpression
prevents the FTY720‐induction of apoptotic stimuli. Furthermore, FTY720 induces G0/G1
cell cycle arrest. The present study further examines the correlation between intracellular
signaling kinases with FTY720‐induced mitochondria‐involved apoptosis. Human T cell
leukemia Jurkat was exposed to FTY720. Dephosphorylation of Akt occurred in a time‐and …
mitochondria‐involved apoptosis in some types of cancer cells, since Bcl‐2 overexpression
prevents the FTY720‐induction of apoptotic stimuli. Furthermore, FTY720 induces G0/G1
cell cycle arrest. The present study further examines the correlation between intracellular
signaling kinases with FTY720‐induced mitochondria‐involved apoptosis. Human T cell
leukemia Jurkat was exposed to FTY720. Dephosphorylation of Akt occurred in a time‐and …
- Our previous studies revealed that the immunosuppressive agent, FTY720, mainly induces mitochondria‐involved apoptosis in some types of cancer cells, since Bcl‐2 overexpression prevents the FTY720‐induction of apoptotic stimuli. Furthermore, FTY720 induces G0/G1 cell cycle arrest. The present study further examines the correlation between intracellular signaling kinases with FTY720‐induced mitochondria‐involved apoptosis.
- Human T cell leukemia Jurkat was exposed to FTY720. Dephosphorylation of Akt occurred in a time‐ and concentration‐dependent manner. FTY720 also induced Bad (Ser136) and ribosomal p70S6 kinase (p70S6k) (Thr389) dephosphorylation.
- FTY720‐induced Akt dephosphorylation was not because of Akt upstream phosphatidylinositol 3′‐kinase (PI 3‐kinase) pathway inhibition.
- FTY720 also induced Akt dephosphorylation in human B cell leukemia BALL‐1. BALL‐1 cells were resistant to FTY720‐induced apoptosis.
- Okadaic acid (OA) inhibited the FTY720‐induced dephosphorylation of Akt and p70S6k, suggesting that FTY720 promotes Ser/Thr protein phosphatase (PP) activity.
- OA partially inhibited FTY720‐induced caspase‐3 activation.
- PP2A or PP2A‐like phosphatase was temporarily activated in cells exposed to FTY720. In addition, FTY720 activated purified PP2A (ABC).
- Overall, the results suggest that FTY720 activated PP2A or PP2A‐like phosphatase and dephosphorylated Akt pathway factors resulting in the enhancement of apoptosis via mitochondria.
British Journal of Pharmacology (2003) 138, 1303–1312. doi:10.1038/sj.bjp.0705182
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