A phytoestrogen diarylheptanoid mediates estrogen receptor/Akt/glycogen synthase kinase 3ß protein-dependent activation of the Wnt/ß-catenin signaling pathway.
J Biol Chem
; 287(43): 36168-78, 2012 Oct 19.
Article
em En
| MEDLINE
| ID: mdl-22936801
ABSTRACT
Estrogen promotes growth in many tissues by activating Wnt/ß-catenin signaling. Recently, ASPP 049, a diarylheptanoid isolated from Curcuma comosa Roxb., has been identified as a phytoestrogen. This investigation determined the involvement of Wnt/ß-catenin signaling in the estrogenic activity of this diarylheptanoid in transfected HEK 293T and in mouse preosteoblastic (MC3T3-E1) cells using a TOPflash luciferase assay and immunofluorescence. ASPP 049 rapidly activated T-cell-specific transcription factor/lymphoid enhancer binding factor-mediated transcription activity and induced ß-catenin accumulation in the nucleus. Interestingly, the effects of ASPP 049 on the transcriptional activity and induction and accumulation of ß-catenin protein in the nucleus of MC3T3-E1 cells were greater compared with estradiol. Activation of ß-catenin in MC3T3-E1 cells was inhibited by ICI 182,780, suggesting that an estrogen receptor is required. In addition, ASPP 049 induced phosphorylations at serine 473 of Akt and serine 9 of GSK-3ß. Moreover, ASPP 049 also induced proliferation and expressions of Wnt target genes Axin2 and Runx2 in MC3T3-E1 cells. In addition, ASPP 049 increased alkaline phosphatase expression, and activity that was abolished by DKK-1, a blocker of the Wnt/ß-catenin receptor. Taken together, these results suggest that ASPP 049 from C. comosa induced osteoblastic cell proliferation and differentiation through ERα-, Akt-, and GSK-3ß-dependent activation of ß-catenin signaling. Our findings provide a scientific rationale for using C. comosa as a dietary supplement to prevent bone loss in postmenopausal women.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diarileptanoides
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Quinase 3 da Glicogênio Sintase
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Receptor alfa de Estrogênio
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Fitoestrógenos
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Proteínas Proto-Oncogênicas c-akt
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Via de Sinalização Wnt
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article