Regulation of subcellular location and activity of Cdc2-cyclinb1 is involved in bendamustine-induced G2 arrest

Bendamustine is a multifunctional alkylating agent for the treatment of multiple myeloma, with the G2/M arrest-induction ability in human multiple myeloma RPMI-8226 cells, but the mechanism remains ambiguous. In this study, we found bendamustine caused the G2 arrest in 24 h, regulated the phosphoryl...

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Detalles Bibliográficos
Autores principales: Lin, Guan-Yu, He, Ling-Juan, Yan, Yan, Wang, Duo-Duo, Zhuang, Kai-Zan, Zhu, Hong, Yang, Bo
Formato: Articulo
Lenguaje:Inglés
Publicado: 2012
Materias:
Farmacia
Bendamustine
Cdc2-CyclinB1 complex
G2 arrest
RPMI-8226
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/25754
http://www.latamjpharm.org/resumenes/31/7/LAJOP_31_7_1_18.pdf
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-25754
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Farmacia
Bendamustine
Cdc2-CyclinB1 complex
G2 arrest
RPMI-8226
spellingShingle Farmacia
Bendamustine
Cdc2-CyclinB1 complex
G2 arrest
RPMI-8226
Lin, Guan-Yu
He, Ling-Juan
Yan, Yan
Wang, Duo-Duo
Zhuang, Kai-Zan
Zhu, Hong
Yang, Bo
Regulation of subcellular location and activity of Cdc2-cyclinb1 is involved in bendamustine-induced G2 arrest
topic_facet Farmacia
Bendamustine
Cdc2-CyclinB1 complex
G2 arrest
RPMI-8226
description Bendamustine is a multifunctional alkylating agent for the treatment of multiple myeloma, with the G2/M arrest-induction ability in human multiple myeloma RPMI-8226 cells, but the mechanism remains ambiguous. In this study, we found bendamustine caused the G2 arrest in 24 h, regulated the phosphorylation status of Cdc2, and blocked the nuclear import of Cdc2-CyclinB1 complex. Pretreatment with ATM/ATR inhibitor caffeine or p38 MAPK inhibitor SB203580 suppressed the phosphorylation of Cdc2 at Thr14/Tyr15 or attenuate the blockade of nuclear import, respectively; however, neither of these two inhibitors nor the combination imposed significant effects on Bendamustine-triggered G2 arrest. Bendamustine-induced blockade of the nuclear translocation dissipated after 48 h, after which, the G2 arrest was maintained through the inhibitory phosphorylation of Cdc2. Taken together, our research suggested that two or more pathways and mechanisms which regulated the cell cycle in a time-dependent manner were involved in the G2 arrest invoked by bendamustine.
format Articulo
Articulo
author Lin, Guan-Yu
He, Ling-Juan
Yan, Yan
Wang, Duo-Duo
Zhuang, Kai-Zan
Zhu, Hong
Yang, Bo
author_facet Lin, Guan-Yu
He, Ling-Juan
Yan, Yan
Wang, Duo-Duo
Zhuang, Kai-Zan
Zhu, Hong
Yang, Bo
author_sort Lin, Guan-Yu
title Regulation of subcellular location and activity of Cdc2-cyclinb1 is involved in bendamustine-induced G2 arrest
title_short Regulation of subcellular location and activity of Cdc2-cyclinb1 is involved in bendamustine-induced G2 arrest
title_full Regulation of subcellular location and activity of Cdc2-cyclinb1 is involved in bendamustine-induced G2 arrest
title_fullStr Regulation of subcellular location and activity of Cdc2-cyclinb1 is involved in bendamustine-induced G2 arrest
title_full_unstemmed Regulation of subcellular location and activity of Cdc2-cyclinb1 is involved in bendamustine-induced G2 arrest
title_sort regulation of subcellular location and activity of cdc2-cyclinb1 is involved in bendamustine-induced g2 arrest
publishDate 2012
url http://sedici.unlp.edu.ar/handle/10915/25754
http://www.latamjpharm.org/resumenes/31/7/LAJOP_31_7_1_18.pdf
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