6,7-di-O-acetylsinococuline (FK-3000) induces G2/M phase arrest in breast carcinomas through p38 MAPK phosphorylation and CDC25B dephosphorylation

Li,Yong-Chun; Kim,Bong-Hee; Cho,Soon-Chang; Bang,Mi-Ae; Kim,Sunmin; Park,Dae-Hun

doi:10.3892/ijo.2014.2739

6,7-di-O-acetylsinococuline (FK-3000) induces G2/M phase arrest in breast carcinomas through p38 MAPK phosphorylation and CDC25B dephosphorylation

Authors:
- Yong-Chun Li
- Bong-Hee Kim
- Soon-Chang Cho
- Mi-Ae Bang
- Sunmin Kim
- Dae-Hun Park
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Affiliations: Department of Oriental Medicine Materials, Dongshin University, Naju, Jeonnam 520-714, Republic of Korea, Chungnam National University, Yuseong, Daejeon 305-764, Republic of Korea, Research Institute, NaturePureKorea Inc., Damyang 517-803, Republic of Korea, Food Industry Development Team, Jeonnam Biofood Technology Center, Naju, Republic of Korea
Published online on: November 7, 2014 https://doi.org/10.3892/ijo.2014.2739
Pages: 578-586
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

We evaluated the cytostatic effect of 6,7-di-O-acetylsinococuline (FK-3000) isolated from Stephania delavayi Diels. against breast carcinoma cell lines MDA-MB‑231 and MCF-7. FK-3000 suppressed CDC25B phosphorylation directly and indirectly via p38 MAPK phosphorylation. CDC25B dephosphorylation decreased levels of cyclin B and phospho-CDC-2, and ultimately induced cell cycle arrest at the G2/M phase. The p38 MAPK inhibitor, SB 239063 blocked FK-3000-induced p38 MAPK phosphorylation and nuclear accumulation, but did not completely rescue cell death. Conclusively FK-3000 exerts its antiproliferative effect through two pathways: i) G2/M cell cycle arrest via downregulation of cyclin B and phospho-CDC2 by p38 MAPK phosphorylation and CDC25B dephosphorylation, and ii) p38 MAPK-independent induction of apoptosis.

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