12-O-Tetradecanoyl phorbol-13-acetate (TPA)-induced growth arrest is increased by silibinin by the down-regulation of cyclin B1 and cdc2 and the up-regulation of p21 expression in MDA-MB231 human breast cancer cells
- Authors
- Kim, S[Kim, Sangmin]; Lee, HS[Lee, Hye Sook]; Lee, SK[Lee, Se-Kyung]; Kim, SH[Kim, Sung Hoon]; Hur, SM[Hur, Sung Mo]; Kim, JS[Kim, Jee Soo]; Kim, JH[Kim, Jung-Han]; Choe, JH[Choe, Jun-Ho]; Shin, I[Shin, Incheol]; Yang, JH[Yang, Jung-Hyun]; Lee, JE[Lee, Jeong Eon]; Nam, SJ[Nam, Seok Jin]
- Issue Date
- 1-Dec-2010
- Publisher
- ELSEVIER GMBH, URBAN & FISCHER VERLAG
- Keywords
- Silibinin; Silybum marianum; TPA; Cyclin B1; Cdc2; p21
- Citation
- PHYTOMEDICINE, v.17, no.14, pp.1127 - 1132
- Indexed
- SCIE
SCOPUS
- Journal Title
- PHYTOMEDICINE
- Volume
- 17
- Number
- 14
- Start Page
- 1127
- End Page
- 1132
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/72572
- DOI
- 10.1016/j.phymed.2010.03.013
- ISSN
- 0944-7113
- 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 pre-treated 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. (C) 2010 Elsevier GmbH. All rights reserved.
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Collections - Medicine > Department of Medicine > 1. Journal Articles
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