Polyamine-depletion induces p27(Kip1) and enhances dexamethasone-induced G1 arrest and apoptosis in human T lymphoblastic leukemia cells

Sang Hyun Choi; Seong Woo Kim; Dong Hee Choi; Bon Hong Min; Boe Gwun Chun

doi:10.1016/S0145-2126(99)00161-7

Polyamine-depletion induces p27(Kip1) and enhances dexamethasone-induced G₁ arrest and apoptosis in human T lymphoblastic leukemia cells

Sang Hyun Choi, Seong Woo Kim, Dong Hee Choi, Bon Hong Min, Boe Gwun Chun

Research output: Contribution to journal › Article › peer-review

28 Citations (Scopus)

Abstract

Glucocorticoid-induced apoptosis is preceded by G₁ arrest and supposed to be up-regulated by polyamine-depletion, which also induces G₁ arrest. In CEM leukemia cells, dexamethasone showed an antileukemic effect by inducing G₁ arrest and apoptosis. DFMO, which depleted cellular polyamines by inhibiting ornithine decarboxylase, induced G₁ arrest but without apoptosis, though it enhanced dexamethasone-induced G₁ arrest and apoptosis. The G₁ arrest was associated with hypophosphorylation of pRb. Dexamethasone inhibited the increase of mutated p53 expression but had little effect on p21(Waf1/Cip1) expression. The p27(Kip1) level was increased by dexamethasone or/and DFMO in line with the kinetics of G₁ arrest. Therefore, the up-regulation of dexamethasone-induced apoptosis by polyamine-depletion may be associated with additive down-regulation of G₁ progression via the p27(Kip1)-pRb pathway.

Original language	English
Pages (from-to)	119-127
Number of pages	9
Journal	Leukemia Research
Volume	24
Issue number	2
DOIs	https://doi.org/10.1016/S0145-2126(99)00161-7
Publication status	Published - 2000 Feb

Keywords

Apoptosis
CEM leukemia cells
DL-α-Difluoromethylornithine
Dexamethasone
G arrest
p27(Kip1)
pRb

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/S0145-2126(99)00161-7

Cite this

@article{62575fae8efd43718da5351f7442252d,

title = "Polyamine-depletion induces p27(Kip1) and enhances dexamethasone-induced G1 arrest and apoptosis in human T lymphoblastic leukemia cells",

abstract = "Glucocorticoid-induced apoptosis is preceded by G1 arrest and supposed to be up-regulated by polyamine-depletion, which also induces G1 arrest. In CEM leukemia cells, dexamethasone showed an antileukemic effect by inducing G1 arrest and apoptosis. DFMO, which depleted cellular polyamines by inhibiting ornithine decarboxylase, induced G1 arrest but without apoptosis, though it enhanced dexamethasone-induced G1 arrest and apoptosis. The G1 arrest was associated with hypophosphorylation of pRb. Dexamethasone inhibited the increase of mutated p53 expression but had little effect on p21(Waf1/Cip1) expression. The p27(Kip1) level was increased by dexamethasone or/and DFMO in line with the kinetics of G1 arrest. Therefore, the up-regulation of dexamethasone-induced apoptosis by polyamine-depletion may be associated with additive down-regulation of G1 progression via the p27(Kip1)-pRb pathway.",

keywords = "Apoptosis, CEM leukemia cells, DL-α-Difluoromethylornithine, Dexamethasone, G arrest, p27(Kip1), pRb",

author = "Choi, {Sang Hyun} and Kim, {Seong Woo} and Choi, {Dong Hee} and Min, {Bon Hong} and Chun, {Boe Gwun}",

note = "Funding Information: S.-H. Choi provided the concept, design, study materials, analysis, interpretation and statistical input. In addition Dr Choi drafted the article and gave final approval. S.-W. Kim provided data analysis and interpretation. D.-H. Choi gave technical support and B.-G. Chun provided assistance in the concept and design, critical revision, helped with the funding and gave final approval. We would like to thank Marion Merrell Dow (Cincinnati, OH) for providing DFMO. This work was supported by the Medical Science Fund from the Medical Science Research Center at Korea University in 1997. ",

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AU - Choi, Sang Hyun

AU - Kim, Seong Woo

AU - Choi, Dong Hee

AU - Min, Bon Hong

AU - Chun, Boe Gwun

N1 - Funding Information: S.-H. Choi provided the concept, design, study materials, analysis, interpretation and statistical input. In addition Dr Choi drafted the article and gave final approval. S.-W. Kim provided data analysis and interpretation. D.-H. Choi gave technical support and B.-G. Chun provided assistance in the concept and design, critical revision, helped with the funding and gave final approval. We would like to thank Marion Merrell Dow (Cincinnati, OH) for providing DFMO. This work was supported by the Medical Science Fund from the Medical Science Research Center at Korea University in 1997.

PY - 2000/2

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N2 - Glucocorticoid-induced apoptosis is preceded by G1 arrest and supposed to be up-regulated by polyamine-depletion, which also induces G1 arrest. In CEM leukemia cells, dexamethasone showed an antileukemic effect by inducing G1 arrest and apoptosis. DFMO, which depleted cellular polyamines by inhibiting ornithine decarboxylase, induced G1 arrest but without apoptosis, though it enhanced dexamethasone-induced G1 arrest and apoptosis. The G1 arrest was associated with hypophosphorylation of pRb. Dexamethasone inhibited the increase of mutated p53 expression but had little effect on p21(Waf1/Cip1) expression. The p27(Kip1) level was increased by dexamethasone or/and DFMO in line with the kinetics of G1 arrest. Therefore, the up-regulation of dexamethasone-induced apoptosis by polyamine-depletion may be associated with additive down-regulation of G1 progression via the p27(Kip1)-pRb pathway.

AB - Glucocorticoid-induced apoptosis is preceded by G1 arrest and supposed to be up-regulated by polyamine-depletion, which also induces G1 arrest. In CEM leukemia cells, dexamethasone showed an antileukemic effect by inducing G1 arrest and apoptosis. DFMO, which depleted cellular polyamines by inhibiting ornithine decarboxylase, induced G1 arrest but without apoptosis, though it enhanced dexamethasone-induced G1 arrest and apoptosis. The G1 arrest was associated with hypophosphorylation of pRb. Dexamethasone inhibited the increase of mutated p53 expression but had little effect on p21(Waf1/Cip1) expression. The p27(Kip1) level was increased by dexamethasone or/and DFMO in line with the kinetics of G1 arrest. Therefore, the up-regulation of dexamethasone-induced apoptosis by polyamine-depletion may be associated with additive down-regulation of G1 progression via the p27(Kip1)-pRb pathway.

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