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Gambogic acid-induced G2/M phase cell-cycle arrest via disturbing CDK7-mediated phosphorylation of CDC2/p34 in human gastric carcinoma BGC-823 cells

Yu, Jun ; Guo, Qing-Long ; You, Qi-Dong ; Zhao, Li ; Gu, Hong-Yan ; Yang, Yong ; Zhang, Hai-wei ; Tan, Zi ; Wang, Xiaotang

Carcinogenesis (New York), 2007-03, Vol.28 (3), p.632-638 [Revista revisada por pares]

Oxford: Oxford University Press

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Título:
Gambogic acid-induced G2/M phase cell-cycle arrest via disturbing CDK7-mediated phosphorylation of CDC2/p34 in human gastric carcinoma BGC-823 cells
Autor: Yu, Jun ; Guo, Qing-Long ; You, Qi-Dong ; Zhao, Li ; Gu, Hong-Yan ; Yang, Yong ; Zhang, Hai-wei ; Tan, Zi ; Wang, Xiaotang
Materias: Carcinogenèse, carcinogènes et anticarcinogènes ; CDC2 Protein Kinase - metabolism ; Cell Division - drug effects ; Cell Line, Tumor ; Cyclin B - metabolism ; Cyclin B1 ; Cyclin-Dependent Kinases - metabolism ; Dose-Response Relationship, Drug ; G2 Phase - drug effects ; Humans ; Kinetics ; Phosphorylation ; Sciences biologiques et medicales ; Sciences medicales ; Stomach Neoplasms - pathology ; Tumeurs ; Xanthones - pharmacology
Es parte de: Carcinogenesis (New York), 2007-03, Vol.28 (3), p.632-638
Notas: ark:/67375/HXZ-M0HT9B8H-R
These authors contributed equally to this work.
istex:9417417EA54B3DC9B814FED9FCCE0EF16BD413CD
Descripción: Molecular mechanisms of cell-cycle arrest caused by gambogic acid (GA), a natural product isolated from the gamboge resin of Garcinia hanburryi tree, have been investigated using BGC-823 human gastric carcinoma cells as a model. Based on our 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazoliumbromide (MTT) assay and flow cytometric analysis, treatment of BGC-823 cells with growth suppressive concentrations of GA caused an irreversible arrest in the G2/M phase of the cell cycle. Western blot analysis demonstrated that GA-induced cell-cycle arrest in BGC-823 cells was associated with a significant decrease in CDC2/p34 synthesis, which led to the accumulation of phosphorylated-Tyr15 (inactive) form of CDC2/p34. Real-time PCR, western blot and kinase activity assays revealed that GA-induced reduction of CDC2/p34 expression was mediated through the inhibition of cyclin-dependent kinase (CDK)-activating kinase (CDK7/cyclin H) activity. In addition, GA-treated cells were shown to have a low level of CDK7 kinase-phosphorylated-Thr161 CDC2/p34 (active). Taken together, our results suggested that the inhibited proliferation of GA-treated BGC-823 cells was associated with the decreased production of CDK7 mRNA and protein, which in turn, resulted in the reduction of CDK7 kinase activity. The reduced CDK7 kinase activity is responsible for the inactivation of CDC2/p34 kinase and the irreversible G2/M phase cell-cycle arrest of human gastric carcinoma BGC-823 cells.
Editor: Oxford: Oxford University Press
Idioma: Inglés;Francés

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Gambogic acid-induced G2/M phase cell-cycle arrest via disturbing CDK7-mediated phosphorylation of CDC2/p34 in human gastric carcinoma BGC-823 cells

Yu, Jun ; Guo, Qing-Long ; You, Qi-Dong ; Zhao, Li ; Gu, Hong-Yan ; Yang, Yong ; Zhang, Hai-wei ; Tan, Zi ; Wang, Xiaotang

Oxford: Oxford University Press

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