Thallium acetate induces C6 glioma cell apoptosis

Chee Fah Chia, Soul-Chin Chen, Chin Shyang Chen, Chuen Ming Shih, Horng Mo Lee, Chih Hsiung Wu

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Thallium acetate is a known neurotoxic agent. In this study, we investigated the mechanisms by which thallium acetate induces cell cycle arrest and cell apoptosis in cultured LC6 glioma cells. Exposure of C6 glioma cells to thallium acetate decreased cell viability as demonstrated by the MTT assay. Incubation of thallium acetate arrested cell cycle progression at the G 2/M phase and caused cellular apoptosis at 300 μM as determined by trypan blue exclusion and flow cytometric analysis. The G2/M arrest was associated with a decrease in expression of CDK2 protein and an upregulation of p53 and the CDK inhibitor p21Cip1, but not p27Kip1. Thallium acetate did not alter the protein levels of cyclin A and B; cyclin D1, D2, and D3; and CDK4 expression in C6 glioma cells. Incubation of C6 glioma cells with thallium acetate upregulated the expression of proapoptotic proteins Bad and Apaf and downregulated the expression of anti-apoptotic proteins Bcl-xL and Bcl-2. In conclusion, these data suggest that thallium acetate inhibits cell cycle progression at G2/M phase by suppressing CDK activity through the p53-mediated induction of the CDK inhibitor p21Cip1. Impairment of cell cycle progression may trigger the activation of a mitochondrial pathway and shifts the balance in the Bcl-2 family toward the proapoptotic members, promoting the formation of the apoptosome and, consequently, apoptosis.

Original languageEnglish
Pages (from-to)523-530
Number of pages8
JournalAnnals of the New York Academy of Sciences
Volume1042
DOIs
Publication statusPublished - 2005

Fingerprint

Glioma
Apoptosis
Cells
Cell Cycle
Cell Division
bcl-Associated Death Protein
Apoptosomes
Cyclin D3
Cyclin D2
Cyclin-Dependent Kinase 2
Cyclin B
Cyclin A
Apoptosis Regulatory Proteins
Trypan Blue
G2 Phase
Cyclin D1
Cell Cycle Checkpoints
thallium acetate
Assays
Cell Survival

Keywords

  • C6 glioma cells
  • GM arrest
  • Mitochondria
  • p21
  • p27
  • Thallium acetate

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

Thallium acetate induces C6 glioma cell apoptosis. / Chia, Chee Fah; Chen, Soul-Chin; Chen, Chin Shyang; Shih, Chuen Ming; Lee, Horng Mo; Wu, Chih Hsiung.

In: Annals of the New York Academy of Sciences, Vol. 1042, 2005, p. 523-530.

Research output: Contribution to journalArticle

Chia, Chee Fah ; Chen, Soul-Chin ; Chen, Chin Shyang ; Shih, Chuen Ming ; Lee, Horng Mo ; Wu, Chih Hsiung. / Thallium acetate induces C6 glioma cell apoptosis. In: Annals of the New York Academy of Sciences. 2005 ; Vol. 1042. pp. 523-530.
@article{85eb0c208d6f4cdb8b101e9a771dcb78,
title = "Thallium acetate induces C6 glioma cell apoptosis",
abstract = "Thallium acetate is a known neurotoxic agent. In this study, we investigated the mechanisms by which thallium acetate induces cell cycle arrest and cell apoptosis in cultured LC6 glioma cells. Exposure of C6 glioma cells to thallium acetate decreased cell viability as demonstrated by the MTT assay. Incubation of thallium acetate arrested cell cycle progression at the G 2/M phase and caused cellular apoptosis at 300 μM as determined by trypan blue exclusion and flow cytometric analysis. The G2/M arrest was associated with a decrease in expression of CDK2 protein and an upregulation of p53 and the CDK inhibitor p21Cip1, but not p27Kip1. Thallium acetate did not alter the protein levels of cyclin A and B; cyclin D1, D2, and D3; and CDK4 expression in C6 glioma cells. Incubation of C6 glioma cells with thallium acetate upregulated the expression of proapoptotic proteins Bad and Apaf and downregulated the expression of anti-apoptotic proteins Bcl-xL and Bcl-2. In conclusion, these data suggest that thallium acetate inhibits cell cycle progression at G2/M phase by suppressing CDK activity through the p53-mediated induction of the CDK inhibitor p21Cip1. Impairment of cell cycle progression may trigger the activation of a mitochondrial pathway and shifts the balance in the Bcl-2 family toward the proapoptotic members, promoting the formation of the apoptosome and, consequently, apoptosis.",
keywords = "C6 glioma cells, GM arrest, Mitochondria, p21, p27, Thallium acetate",
author = "Chia, {Chee Fah} and Soul-Chin Chen and Chen, {Chin Shyang} and Shih, {Chuen Ming} and Lee, {Horng Mo} and Wu, {Chih Hsiung}",
year = "2005",
doi = "10.1196/annals.1338.064",
language = "English",
volume = "1042",
pages = "523--530",
journal = "Annals of the New York Academy of Sciences",
issn = "0077-8923",
publisher = "Blackwell Publishing Ltd",

}

TY - JOUR

T1 - Thallium acetate induces C6 glioma cell apoptosis

AU - Chia, Chee Fah

AU - Chen, Soul-Chin

AU - Chen, Chin Shyang

AU - Shih, Chuen Ming

AU - Lee, Horng Mo

AU - Wu, Chih Hsiung

PY - 2005

Y1 - 2005

N2 - Thallium acetate is a known neurotoxic agent. In this study, we investigated the mechanisms by which thallium acetate induces cell cycle arrest and cell apoptosis in cultured LC6 glioma cells. Exposure of C6 glioma cells to thallium acetate decreased cell viability as demonstrated by the MTT assay. Incubation of thallium acetate arrested cell cycle progression at the G 2/M phase and caused cellular apoptosis at 300 μM as determined by trypan blue exclusion and flow cytometric analysis. The G2/M arrest was associated with a decrease in expression of CDK2 protein and an upregulation of p53 and the CDK inhibitor p21Cip1, but not p27Kip1. Thallium acetate did not alter the protein levels of cyclin A and B; cyclin D1, D2, and D3; and CDK4 expression in C6 glioma cells. Incubation of C6 glioma cells with thallium acetate upregulated the expression of proapoptotic proteins Bad and Apaf and downregulated the expression of anti-apoptotic proteins Bcl-xL and Bcl-2. In conclusion, these data suggest that thallium acetate inhibits cell cycle progression at G2/M phase by suppressing CDK activity through the p53-mediated induction of the CDK inhibitor p21Cip1. Impairment of cell cycle progression may trigger the activation of a mitochondrial pathway and shifts the balance in the Bcl-2 family toward the proapoptotic members, promoting the formation of the apoptosome and, consequently, apoptosis.

AB - Thallium acetate is a known neurotoxic agent. In this study, we investigated the mechanisms by which thallium acetate induces cell cycle arrest and cell apoptosis in cultured LC6 glioma cells. Exposure of C6 glioma cells to thallium acetate decreased cell viability as demonstrated by the MTT assay. Incubation of thallium acetate arrested cell cycle progression at the G 2/M phase and caused cellular apoptosis at 300 μM as determined by trypan blue exclusion and flow cytometric analysis. The G2/M arrest was associated with a decrease in expression of CDK2 protein and an upregulation of p53 and the CDK inhibitor p21Cip1, but not p27Kip1. Thallium acetate did not alter the protein levels of cyclin A and B; cyclin D1, D2, and D3; and CDK4 expression in C6 glioma cells. Incubation of C6 glioma cells with thallium acetate upregulated the expression of proapoptotic proteins Bad and Apaf and downregulated the expression of anti-apoptotic proteins Bcl-xL and Bcl-2. In conclusion, these data suggest that thallium acetate inhibits cell cycle progression at G2/M phase by suppressing CDK activity through the p53-mediated induction of the CDK inhibitor p21Cip1. Impairment of cell cycle progression may trigger the activation of a mitochondrial pathway and shifts the balance in the Bcl-2 family toward the proapoptotic members, promoting the formation of the apoptosome and, consequently, apoptosis.

KW - C6 glioma cells

KW - GM arrest

KW - Mitochondria

KW - p21

KW - p27

KW - Thallium acetate

UR - http://www.scopus.com/inward/record.url?scp=22044437580&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=22044437580&partnerID=8YFLogxK

U2 - 10.1196/annals.1338.064

DO - 10.1196/annals.1338.064

M3 - Article

C2 - 15965099

AN - SCOPUS:22044437580

VL - 1042

SP - 523

EP - 530

JO - Annals of the New York Academy of Sciences

JF - Annals of the New York Academy of Sciences

SN - 0077-8923

ER -