Chrysin induces G1 phase cell cycle arrest in C6 glioma cells through inducing p21Waf1/Cip1 expression

Involvement of p38 mitogen-activated protein kinase

Meng Shih Weng, Yuan Soon Ho, Jen Kun Lin

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Flavonoids are a broadly distributed class of plant pigments, universally present in plants. They are strong anti-oxidants that can inhibit carcinogenesis in rodents. Chrysin (5,7-dihydroxyflavone) is a natural and biologically active compound extracted from many plants, honey, and propolis. It possesses potent anti-inflammatory, anti-oxidant properties, promotes cell death, and perturbing cell cycle progression. However, the mechanism by which chrysin inhibits cancer cell growth remains poorly understood. Therefore, we developed an interest in the relationship between MAPK signaling pathways and cell growth inhibition after chrysin treatment in rat C6 glioma cells. Cell viability assay and flow cytometric analysis suggested that chrysin exhibited a dose-dependent and time-dependent ability to block rat C6 glioma cell line cell cycle progression at the G1 phase. Western blotting analysis showed that the levels of Rb phosphorylation in C6 glioma cells exposed to 30 μM chrysin for 24 h decreased significantly. We demonstrated the expression of cyclin-dependent kinase inhibitor, p21Waf1/Cip1, to be significantly increased, but the p53 protein level did not change in chrysin-treated cells. Both cyclin-dependent kinase 2 (CDK2) and 4 (CDK4) kinase activities were reduced by chrysin in a dose-dependent manner. Furthermore, chrysin also inhibited proteasome activity. We further showed that chrysin induced p38-MAPK activation, and using a specific p38-MAPK inhibitor, SB203580, attenuated chrysin-induced p21Waf1/Cip1 expression. These results suggest that chrysin exerts its growth-inhibitory effects either through activating p38-MAPK leading to the accumulation of p21Waf1/Cip1 protein or mediating the inhibition of proteasome activity.

Original languageEnglish
Pages (from-to)1815-1827
Number of pages13
JournalBiochemical Pharmacology
Volume69
Issue number12
DOIs
Publication statusPublished - Jun 15 2005

Fingerprint

G1 Phase Cell Cycle Checkpoints
G1 Phase
p38 Mitogen-Activated Protein Kinases
Glioma
Cells
Cell growth
Proteasome Endopeptidase Complex
Oxidants
chrysin
Rats
Cell Cycle
Growth
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinase 2
Propolis
Phosphorylation
Honey
Cyclin-Dependent Kinases
Cell death
Flavonoids

Keywords

  • Cell cycle
  • Chrysin
  • p21
  • p38-MAPK
  • Proteasome activity

ASJC Scopus subject areas

  • Pharmacology

Cite this

Chrysin induces G1 phase cell cycle arrest in C6 glioma cells through inducing p21Waf1/Cip1 expression : Involvement of p38 mitogen-activated protein kinase. / Weng, Meng Shih; Ho, Yuan Soon; Lin, Jen Kun.

In: Biochemical Pharmacology, Vol. 69, No. 12, 15.06.2005, p. 1815-1827.

Research output: Contribution to journalArticle

@article{94607844bb1143489e49983639f07dde,
title = "Chrysin induces G1 phase cell cycle arrest in C6 glioma cells through inducing p21Waf1/Cip1 expression: Involvement of p38 mitogen-activated protein kinase",
abstract = "Flavonoids are a broadly distributed class of plant pigments, universally present in plants. They are strong anti-oxidants that can inhibit carcinogenesis in rodents. Chrysin (5,7-dihydroxyflavone) is a natural and biologically active compound extracted from many plants, honey, and propolis. It possesses potent anti-inflammatory, anti-oxidant properties, promotes cell death, and perturbing cell cycle progression. However, the mechanism by which chrysin inhibits cancer cell growth remains poorly understood. Therefore, we developed an interest in the relationship between MAPK signaling pathways and cell growth inhibition after chrysin treatment in rat C6 glioma cells. Cell viability assay and flow cytometric analysis suggested that chrysin exhibited a dose-dependent and time-dependent ability to block rat C6 glioma cell line cell cycle progression at the G1 phase. Western blotting analysis showed that the levels of Rb phosphorylation in C6 glioma cells exposed to 30 μM chrysin for 24 h decreased significantly. We demonstrated the expression of cyclin-dependent kinase inhibitor, p21Waf1/Cip1, to be significantly increased, but the p53 protein level did not change in chrysin-treated cells. Both cyclin-dependent kinase 2 (CDK2) and 4 (CDK4) kinase activities were reduced by chrysin in a dose-dependent manner. Furthermore, chrysin also inhibited proteasome activity. We further showed that chrysin induced p38-MAPK activation, and using a specific p38-MAPK inhibitor, SB203580, attenuated chrysin-induced p21Waf1/Cip1 expression. These results suggest that chrysin exerts its growth-inhibitory effects either through activating p38-MAPK leading to the accumulation of p21Waf1/Cip1 protein or mediating the inhibition of proteasome activity.",
keywords = "Cell cycle, Chrysin, p21, p38-MAPK, Proteasome activity",
author = "Weng, {Meng Shih} and Ho, {Yuan Soon} and Lin, {Jen Kun}",
year = "2005",
month = "6",
day = "15",
doi = "10.1016/j.bcp.2005.03.011",
language = "English",
volume = "69",
pages = "1815--1827",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
number = "12",

}

TY - JOUR

T1 - Chrysin induces G1 phase cell cycle arrest in C6 glioma cells through inducing p21Waf1/Cip1 expression

T2 - Involvement of p38 mitogen-activated protein kinase

AU - Weng, Meng Shih

AU - Ho, Yuan Soon

AU - Lin, Jen Kun

PY - 2005/6/15

Y1 - 2005/6/15

N2 - Flavonoids are a broadly distributed class of plant pigments, universally present in plants. They are strong anti-oxidants that can inhibit carcinogenesis in rodents. Chrysin (5,7-dihydroxyflavone) is a natural and biologically active compound extracted from many plants, honey, and propolis. It possesses potent anti-inflammatory, anti-oxidant properties, promotes cell death, and perturbing cell cycle progression. However, the mechanism by which chrysin inhibits cancer cell growth remains poorly understood. Therefore, we developed an interest in the relationship between MAPK signaling pathways and cell growth inhibition after chrysin treatment in rat C6 glioma cells. Cell viability assay and flow cytometric analysis suggested that chrysin exhibited a dose-dependent and time-dependent ability to block rat C6 glioma cell line cell cycle progression at the G1 phase. Western blotting analysis showed that the levels of Rb phosphorylation in C6 glioma cells exposed to 30 μM chrysin for 24 h decreased significantly. We demonstrated the expression of cyclin-dependent kinase inhibitor, p21Waf1/Cip1, to be significantly increased, but the p53 protein level did not change in chrysin-treated cells. Both cyclin-dependent kinase 2 (CDK2) and 4 (CDK4) kinase activities were reduced by chrysin in a dose-dependent manner. Furthermore, chrysin also inhibited proteasome activity. We further showed that chrysin induced p38-MAPK activation, and using a specific p38-MAPK inhibitor, SB203580, attenuated chrysin-induced p21Waf1/Cip1 expression. These results suggest that chrysin exerts its growth-inhibitory effects either through activating p38-MAPK leading to the accumulation of p21Waf1/Cip1 protein or mediating the inhibition of proteasome activity.

AB - Flavonoids are a broadly distributed class of plant pigments, universally present in plants. They are strong anti-oxidants that can inhibit carcinogenesis in rodents. Chrysin (5,7-dihydroxyflavone) is a natural and biologically active compound extracted from many plants, honey, and propolis. It possesses potent anti-inflammatory, anti-oxidant properties, promotes cell death, and perturbing cell cycle progression. However, the mechanism by which chrysin inhibits cancer cell growth remains poorly understood. Therefore, we developed an interest in the relationship between MAPK signaling pathways and cell growth inhibition after chrysin treatment in rat C6 glioma cells. Cell viability assay and flow cytometric analysis suggested that chrysin exhibited a dose-dependent and time-dependent ability to block rat C6 glioma cell line cell cycle progression at the G1 phase. Western blotting analysis showed that the levels of Rb phosphorylation in C6 glioma cells exposed to 30 μM chrysin for 24 h decreased significantly. We demonstrated the expression of cyclin-dependent kinase inhibitor, p21Waf1/Cip1, to be significantly increased, but the p53 protein level did not change in chrysin-treated cells. Both cyclin-dependent kinase 2 (CDK2) and 4 (CDK4) kinase activities were reduced by chrysin in a dose-dependent manner. Furthermore, chrysin also inhibited proteasome activity. We further showed that chrysin induced p38-MAPK activation, and using a specific p38-MAPK inhibitor, SB203580, attenuated chrysin-induced p21Waf1/Cip1 expression. These results suggest that chrysin exerts its growth-inhibitory effects either through activating p38-MAPK leading to the accumulation of p21Waf1/Cip1 protein or mediating the inhibition of proteasome activity.

KW - Cell cycle

KW - Chrysin

KW - p21

KW - p38-MAPK

KW - Proteasome activity

UR - http://www.scopus.com/inward/record.url?scp=20344388264&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20344388264&partnerID=8YFLogxK

U2 - 10.1016/j.bcp.2005.03.011

DO - 10.1016/j.bcp.2005.03.011

M3 - Article

VL - 69

SP - 1815

EP - 1827

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 12

ER -