Abstract |
TPA is a potent regulator of cell growth, including cell proliferation and differentiation. In this study, we determined the effect of silibinin on TPA-induced growth arrest in breast cancer cells. Silibinin increased growth arrest of the G2/M phase in a dose-dependent fashion. Silibinin decreased the basal level of cyclin B1 and cdc2 expression, which is involved in S phase and G2/M transition. In addition, TPA-induced G2/M phase arrest was increased by silibinin. Under the same conditions, TPA-induced down-regulation of cyclin B1 and cdc2 was decreased by silibinin. In contrast, TPA-induced p21 expression was further increased by silibinin. To determine the regulatory mechanism of TPA-induced growth arrest, we pretreated cells with various inhibitors, such as UO126, SB203580, and LY294002. Interestingly, TPA-induced growth arrest was significantly increased by LY294002, but not by UO126 and SB203580. In addition, TPA-induced down-regulation of cyclin B1 was inhibited by LY294002; however, the basal level of p21 was increased by TPA and TPA-induced p21 expression was further increased by LY294002. Finally, adenoviral constitutively active-Akt (Ad-CA-Akt) overexpression regulated the up-regulation of cyclin B1 and the down-regulation of p21. Therefore, we have demonstrated that silibinin has an additive effect on TPA-induced growth arrest through the PI-3-kinase/Akt-dependent pathway.
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Authors | Sangmin Kim, Hye Sook Lee, Se-Kyung Lee, Sung Hoon Kim, Sung Mo Hur, Jee Soo Kim, Jung-Han Kim, Jun-Ho Choe, Incheol Shin, Jung-Hyun Yang, Jeong Eon Lee, Seok Jin Nam |
Journal | Phytomedicine : international journal of phytotherapy and phytopharmacology
(Phytomedicine)
Vol. 17
Issue 14
Pg. 1127-32
(Dec 01 2010)
ISSN: 1618-095X [Electronic] Germany |
PMID | 20554189
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2010 Elsevier GmbH. All rights reserved. |
Chemical References |
- Antineoplastic Agents, Phytogenic
- Cell Cycle Proteins
- Cyclin B1
- Cyclin-Dependent Kinase Inhibitor p21
- Enzyme Inhibitors
- Plant Extracts
- Silymarin
- Croton Oil
- Phosphatidylinositol 3-Kinases
- Proto-Oncogene Proteins c-akt
- CDC2 Protein Kinase
- Cdk1 protein, rat
- Cyclin-Dependent Kinases
- Tetradecanoylphorbol Acetate
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Topics |
- Antineoplastic Agents, Phytogenic
(pharmacology, therapeutic use)
- Breast Neoplasms
(drug therapy, metabolism)
- CDC2 Protein Kinase
- Cell Cycle
(drug effects)
- Cell Cycle Proteins
(metabolism)
- Cell Line, Tumor
- Croton Oil
(chemistry)
- Cyclin B1
(metabolism)
- Cyclin-Dependent Kinase Inhibitor p21
(metabolism)
- Cyclin-Dependent Kinases
- Drug Synergism
- Drug Therapy, Combination
- Enzyme Inhibitors
(pharmacology)
- Female
- Gene Expression Regulation, Neoplastic
(drug effects)
- Humans
- Silybum marianum
(chemistry)
- Phosphatidylinositol 3-Kinases
(metabolism)
- Phytotherapy
- Plant Extracts
(pharmacology, therapeutic use)
- Proto-Oncogene Proteins c-akt
(metabolism)
- Signal Transduction
(drug effects)
- Silymarin
(pharmacology, therapeutic use)
- Tetradecanoylphorbol Acetate
(pharmacology, therapeutic use)
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