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

  • Int J Oncol. 2015 Feb;46(2):578-86. doi: 10.3892/ijo.2014.2739.
Yong-Chun Li  1 ,  Bong-Hee Kim  2 ,  Soon-Chang Cho  3 ,  Mi-Ae Bang  4 ,  Sunmin Kim  1 ,  Dae-Hun Park  1
Affiliations
  • 1. Department of Oriental Medicine Materials, Dongshin University, Naju, Jeonnam 520-714, Republic of Korea.
  • 2. Chungnam National University, Yuseong, Daejeon 305-764, Republic of Korea.
  • 3. Research Institute, NaturePureKorea Inc., Damyang 517-803, Republic of Korea.
  • 4. Food Industry Development Team, Jeonnam Biofood Technology Center, Naju, Republic of Korea.
PMID: 25384584 DOI: 10.3892/ijo.2014.2739
Abstract

We evaluated the cytostatic effect of 6,7-di-O-acetyl-sinococuline (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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