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A Withanolide Coagulin-L Inhibits Adipogenesis Modulating Wnt/βCatenin and Cell Cycle Arrest in Mitotic Clonal Expansion

IR@CDRI: CSIR-Central Drug Research Institute, Lucknow

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Creator Beg, Muheeb
Chauhan, Parul
Varshney, Salil
Shankar, Kripa
Rajan, Sujith
Saini, Deepika
Srivastava, M N
Yadav, P P
Gaikwad, A N
 
Date 2014-12-04T11:11:05Z
2014-12-04T11:11:05Z
2014
 
Identifier Phytomedicine,2014, 21(4),406-14
http://hdl.handle.net/123456789/1425
 
Description Obesity is a result of adipocyte hypertrophy followed by hyperplasia. It is a risk factor for several metabolic disorders such as dyslipidemia, type-2 diabetes, hypertension, and cardiovascular diseases. Coagulanolides, particularly coagulin-L isolated from W. coagulan has earlier been reported for anti-hyperglycemic activity. In this study, we investigated effect of coagulin-L on in-vitro models of adipocyte differentiation including 3T3-L1 pre-adipocyte, mouse stromal mesenchymal C3H10T1/2 cells and bone marrow derived human mesenchymal stem cells (hMSCs). Our results showed that, coagulin-L reduces the expressions of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), the major transcription factors orchestrating adipocyte differentiation. Detailed analysis further proved that early exposure of coagulin-L is sufficient to cause significant inhibition during adipogenesis. Coagulin-L inhibited mitotic clonal expansion (MCE) by delayed entry in G1 to S phase transition and S-phase arrest. This MCE blockade was caused apparently by decreased phosophorylation of C/EBPβ, modulation in expression of cell cycle regulatory proteins, and upregulation of Wnt/βcatenin pathway, the early stage regulatory proteins of adipogenic induction. Taken together all evidences, a known anti-hyperglycemic agent coagulin-L has shown potential to inhibit adipogenesis significantly, which can be therapeutically exploited for treatment of obesity and metabolic syndrome.
 
Format 832395 bytes
application/pdf
 
Language en
 
Relation CSIR-CDRI communication No. 8557
 
Subject Coagulin-L
Mitotic clonal expansion
Obesity
3T3-L1
Adipocytes
Adipogenesis
 
Title A Withanolide Coagulin-L Inhibits Adipogenesis Modulating Wnt/βCatenin and Cell Cycle Arrest in Mitotic Clonal Expansion
 
Type Article