Abstract
Pentagalloylglucose (5GG) is a potent and specific inhibitor of NADPH dehydrogenase or xanthine oxidase. In our previous study, we showed that 5GG was able to induce apoptosis in HL-60 cells in a time- and concentration-dependent manner via the activation of caspase-3. Recently, we found that 5GG was capable of perturbing the cell cycle of the human breast cancer cell line MCF-7. DNA flow cytometric analysis showed that 5GG exhibited the ability of blocking MCF-7 cell cycle progression at the G1 phase. The level of several G1 phase-related cyclins and cyclin-dependent kinases did not change in these cells during a 24-hr exposure to 5GG. However, the activity of cyclin E/CDK2 was decreased in a concentration- and time-dependent manner and the activity of cyclin D/CDK4 was inhibited when serum-starved synchronized cells were released from synchronization. p27(Kip) and p21(Cip), inhibitors of cyclin/CDK complexes in G1-phase, were gradually increased after 5GG treatment in a time-dependent manner and the induction of p21(Cip) was correlated with an increase in p53 levels. These results suggest that the suppression of cell-cycle progression in the G1 phase by 5GG was mediated in MCF-7 cells, at least in part, by either the inhibition of cyclin D/CDK4 and cyclin E/CDK2 activity or the induction of the CDK inhibitors p27(Kip) and p21(Cip).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Breast Neoplasms / pathology
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CDC2-CDC28 Kinases*
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cell Division / drug effects
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Cyclin D
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Cyclin E / metabolism
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclin-Dependent Kinase Inhibitor p27
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Cyclin-Dependent Kinases / antagonists & inhibitors
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Cyclin-Dependent Kinases / metabolism*
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Cyclins / genetics
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Cyclins / metabolism*
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DNA / drug effects
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DNA / metabolism
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Down-Regulation
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Enzyme Activation / drug effects
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G1 Phase / drug effects*
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G1 Phase / physiology
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Humans
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Hydrolyzable Tannins / analogs & derivatives*
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Hydrolyzable Tannins / pharmacology*
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Phosphorylation
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Protein Serine-Threonine Kinases / metabolism*
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Proto-Oncogene Proteins*
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Retinoblastoma Protein / metabolism
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Transcription, Genetic / drug effects
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Tumor Cells, Cultured
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
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Up-Regulation
Substances
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CDKN1A protein, human
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Cell Cycle Proteins
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Cyclin D
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Cyclin E
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Hydrolyzable Tannins
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Proto-Oncogene Proteins
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RNA, Messenger
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Retinoblastoma Protein
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Tumor Suppressor Proteins
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Cyclin-Dependent Kinase Inhibitor p27
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pentagalloylglucose
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DNA
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Protein Serine-Threonine Kinases
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CDC2-CDC28 Kinases
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CDK2 protein, human
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CDK4 protein, human
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinases