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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2009.1
- 수록면
- 665 - 677 (13page)
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The JNK inhibitor SP600125 strongly inhibits cell proliferation
in many human cancer cells by blocking
cell-cycle progression and inducing apoptosis. Despite
extensive study, the mechanism by which SP600125
inhibits mitosis-related effects in human leukemia
cells remains unclear. We investigated the effects of
SP600125 on the inhibition of cell proliferation and the
cell cycle, and on microtubule dynamics in vivo and in
vitro. Treatment of synchronized leukemia cells with
varying concentrations of SP600125 results in significant
G2/M cell cycle arrest with elevated p21 levels,
phosphorylation of histone H3 within 24 h, and endoreduplication
with elevated Cdk2 protein levels after 48
h. SP600125 also induces significant abnormal microtubule
dynamics in vivo. High concentrations of
SP600125 (200 μM) were required to disorganize microtubule
polymerization in vitro. Additionally, SP600125-
induced delayed apoptosis and cell death was accompanied
by significant poly ADP-ribose polymerase
(PARP) cleavage and caspase-3 activity in the late
phase (at 72 h). Endoreduplication showed a greater increase
in ectopic Bcl-2-expressing U937 cells at 72 h
than in wild-type U937 cells without delayed apoptosis.
These results indicate that Bcl-2 suppresses apoptosis
and SP600125-induced G2/M arrest and endoreduplication.
Therefore, we suggest that SP600125 induces
mitotic arrest by inducing abnormal spindle microtubule
dynamics.
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등록된 정보가 없습니다.
참고문헌 (23)
참고문헌 신청
Andreassen PR / 1996 / Chemical induction of mitotic checkpoint override in mammalian cells results in aneuploidy following a transient tetraploid state / Mutat Res 372 : 181
Bates S / 1998 / Cell cycle arrest and DNA endoreduplication following p21Waf1/Cip1 expression / Oncogene 17 : 1691 ~ 1703
Cantero G / 2006 / Cisplatin-induced endoreduplication in CHO cells: DNA damage and inhibition of topoisomerase II / Mutat Res 599 : 160 ~ 166
Chang BD / 2000 / p21Waf1/Cip1/Sdi1-induced growth arrest is associated with depletion of mitosis-control proteins and leads to abnormal mitosis and endoreduplication in reco
Cortes F / 2004 / Toward a comprehensive model for induced endoreduplication / Life Sci 76 : 121 ~ 135
Bates S / 1998 / Cell cycle arrest and DNA endoreduplication following p21Waf1/Cip1 expression / Oncogene 17 : 1691 ~ 1703
Cantero G / 2006 / Cisplatin-induced endoreduplication in CHO cells: DNA damage and inhibition of topoisomerase II / Mutat Res 599 : 160 ~ 166
Chang BD / 2000 / p21Waf1/Cip1/Sdi1-induced growth arrest is associated with depletion of mitosis-control proteins and leads to abnormal mitosis and endoreduplication in reco
Cortes F / 2004 / Toward a comprehensive model for induced endoreduplication / Life Sci 76 : 121 ~ 135
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