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Deguelin suppresses cell proliferation via the inhibition of survivin expression and STAT3 phosphorylation in HTLV-1-transformed T cells.
- Source :
-
Leukemia research [Leuk Res] 2010 Mar; Vol. 34 (3), pp. 352-7. Date of Electronic Publication: 2009 Sep 24. - Publication Year :
- 2010
-
Abstract
- Adult T-cell leukemia (ATL) is an aggressive malignancy of peripheral T cells infected with human T-cell leukemia virus type 1 (HTLV-1). The prognosis of aggressive ATL patients remains poor because of its resistance to conventional chemotherapy. We examined the effect of deguelin, a naturally occurring rotenoid, on HTLV-1-transformed T-cell lines, KUT-1 and MT-2 cells. We found that deguelin suppressed cell proliferation and induced cell death in these cells. Immunoblot analysis showed the inhibition of survivin expression and signal transducers, and activators of transcription (STAT) 3 phosphorylation of both cells. We also observed the cleavage of caspase-3 and poly(ADP-ribose) polymerase (PARP) in deguelin-treated cells, indicating that deguelin induces caspase-dependent apoptosis in these cells. Furthermore, proteasome inhibitor MG132 prevented the down-regulation of survivin expression and STAT3 dephosphorylation by deguelin, suggesting that the action mechanism of deguelin involves the degradation of survivin and phosphorylated STAT3 through the ubiquitin/proteasome pathway. Our data indicate that deguelin presents a potent anti-proliferative effect in part via the down-regulation of survivin expression and STAT3 phosphorylation in HTLV-1-transformed cells. Deguelin merits further investigation as a potential chemotherapeutic agent for ATL.<br /> (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)
- Subjects :
- Apoptosis drug effects
Blotting, Western
Cell Line
Cell Transformation, Viral drug effects
Down-Regulation
Humans
Inhibitor of Apoptosis Proteins
Microtubule-Associated Proteins biosynthesis
Phosphorylation
Reverse Transcriptase Polymerase Chain Reaction
Rotenone pharmacology
STAT3 Transcription Factor metabolism
Signal Transduction drug effects
Survivin
T-Lymphocytes drug effects
T-Lymphocytes virology
Antineoplastic Agents pharmacology
Cell Proliferation drug effects
HTLV-I Infections drug therapy
Microtubule-Associated Proteins drug effects
Rotenone analogs & derivatives
STAT3 Transcription Factor drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1873-5835
- Volume :
- 34
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Leukemia research
- Publication Type :
- Academic Journal
- Accession number :
- 19781773
- Full Text :
- https://doi.org/10.1016/j.leukres.2009.09.003