6,7-di-O-acetylsinococuline (FK-3000) induces G2/M phase arrest in breast carcinomas through p38 MAPK phosphorylation and CDC25B dephosphorylation.
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.
Department of Oriental Medicine Materials, Dongshin University, Naju, Jeonnam 520-714, Republic of Korea.
Yong-Chun
YC
Li
Chungnam National University, Yuseong, Daejeon 305-764, Republic of Korea.
Bong-Hee
BH
Kim
Research Institute, NaturePureKorea Inc., Damyang 517-803, Republic of Korea.
Soon-Chang
SC
Cho
Food Industry Development Team, Jeonnam Biofood Technology Center, Naju, Republic of Korea.
Mi-Ae
MA
Bang
Department of Oriental Medicine Materials, Dongshin University, Naju, Jeonnam 520-714, Republic of Korea.
Sunmin
S
Kim
Department of Oriental Medicine Materials, Dongshin University, Naju, Jeonnam 520-714, Republic of Korea.
Dae-Hun
DH
Park
D000470:Alkaloids / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D010766:Phosphorylation; D020687:cdc25 Phosphatases / Q000096:biosynthesis*; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis* / Q000235:genetics
D000470:Alkaloids; C442856:FK3000; D048051:p38 Mitogen-Activated Protein Kinases; C517008:CDC25B protein, human; D020687:cdc25 Phosphatases