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Genistein-induced apoptosis via Akt signaling pathway in anaplastic large-cell lymphoma

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Authors
Park, Sung-Shin; Kim, Yong-Nyun; Jeon, Yoon Kyung; Kim, Young A; Kim, Ji Eun; Kim, Heejung; Kim, Chul Woo
Issue Date
2005-05-10
Publisher
Springer Verlag
Citation
Cancer Chemother Pharmacol 56:271.
Keywords
Anaplastic large cell lymphomaGenisteinApoptosisAktCaspase
Abstract
More than half of anaplastic large-cell lymphoma
(ALCL) are associated with chromosomal
translocation t(2;5)(p23;q35) that leads to the expression
of nucleophosmin-anaplastic lymphoma kinase (NPMALK)
oncoprotein. NPM-ALK activates the antiapoptotic
phosphatidylinositol-3 kinase/Akt (PI3K/Akt) signaling
pathway, which plays a critical role in cell
survival and apoptosis. Inhibition of the PI3K/Akt
pathway has been considered as a therapeutic target for
cancer where PI3K/Akt activation is a causative factor.
Genistein, a natural isoflavonoid found in soy products,
has been shown to inhibit cell growth and induce
apoptosis in a wide variety of cell lines. Here, we demonstrated
that treatment of two t(2;5) ALCL cell lines,
SUDHL-1 and Karpas299, with genistein induced
apoptosis in a time- and dose-dependent manner. Concurrently,
these cells exhibited a decrease in Akt protein
levels and subsequent downregulation of Akt activity
(Akt phosphorylation). Furthermore, genistein treatment
induced mitochondrial membrane potential
change, caspase-3 activation and PARP cleavage. From
these results, we conclude that inhibition of the Akt
signaling pathway and induction of apoptosis by genistein
could be used as a new treatment modality for the
prevention and/or treatment of t(2;5) ALCL and other
hematopoietic malignancies.
ISSN
0344-5704 (print)
1432-0843 (online)
Language
English
URI
http://hdl.handle.net/10371/10349
DOI
https://doi.org/10.1007/s00280-004-0974-z
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College of Medicine/School of Medicine (의과대학/대학원)Pathology (병리학전공)Journal Papers (저널논문_병리학전공)
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