产品号 #100-0252_C
维甲酸受体（RAR）通路抑制剂；抑制法尼醇X受体（FXR）
总览
(Z)- 香胶甾酮是一种植物类固醇，存在于古谷植物Commiphora mukul的树脂中，作为法尼醇X受体的选择性拮抗剂；(FXR；Cui et al.)。在100 μM的鹅去氧胆酸存在下，它降低了鹅去氧胆酸诱导的FXR活化（IC₅₀= 10 μM） (Cui et al.；Urizar et al.）。
分化
·诱导人类多能干细胞产生的神经干细胞分化为多巴胺能神经元（Gonzalez et al.）。
新陈代谢
·降低喂食高胆固醇饮食的啮齿动物肝脏低密度脂蛋白胆固醇和甘油三酯水平（Urizar et al.）。
癌症研究
·通过表达STAT3调控的抗凋亡（Bcl-2、Bcl-xL和Mcl-1）、增殖（cyclin D1）和血管生成（VEGF）基因产物，调节人多发性骨髓瘤细胞中肿瘤细胞的生长和转移（Ahn et al.）。
·抑制人脐静脉内皮细胞（HUVECs）的管状形成和迁移,或人前列腺癌细胞系的迁移（Xiao et al.）。
细胞类型
癌细胞及细胞系，肝细胞，多能干细胞
应用
分化
研究领域
癌症，代谢，干细胞生物学
CAS 编号
39025-23-5
化学式
C₂₁H₂₈O₂
分子量
312.5 克/摩尔
纯度
≥98%
靶点
FXR
Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
Resources and Publications
Publications (5)
Deriving dopaminergic neurons for clinical use. A practical approach. Scientific reports 2013 JAN
Abstract
New small molecules that regulate the step-wise differentiation of human pluripotent stem cells into dopaminergic neurons have been identified. The steroid, guggulsterone, was found to be the most effective inducer of neural stem cells into dopaminergic neurons. These neurons are extensively characterized and shown to be functional. We believe this new approach offers a practical route to creating neurons of sufficient quality to be used to treat Parkinson's disease patients.
Guggulsterone, a farnesoid X receptor antagonist, inhibits constitutive and inducible STAT3 activation through induction of a protein tyrosine phosphatase SHP-1. Cancer research 2008 jun
Abstract
Signal transducers and activator of transcription 3 (STAT3) is a transcription factor that has been associated with survival, proliferation, chemoresistance, and angiogenesis of tumor cells. Whether the apoptotic, antiproliferative, and antimetastatic effects of guggulsterone (GS), a farnesoid X receptor antagonist, are linked to its ability to suppress STAT3 activation was investigated. We found that the Z but not the E stereoisomer of GS inhibited both constitutive and interleukin-6-induced STAT3 activation in human multiple myeloma cells. The suppression of STAT3 was mediated through the inhibition of activation of protein tyrosine kinases Janus-activated kinase 2 and c-Src. Vanadate treatment reversed the GS-induced down-regulation of STAT3, suggesting the involvement of a protein tyrosine phosphatase. Indeed, we found that GS induced the expression of both the protein and mRNA for tyrosine protein phosphatase SHP-1 that was not due to demethylation of the SHP-1 promoter previously implicated in the epigenetic silencing of SHP-1. Moreover, knockdown of SHP-1 by small interfering RNA suppressed the effect of GS on induction of SHP-1 and on the inhibition of STAT3 activation, thereby implicating SHP-1 in the action of GS. Finally, GS down-regulated the expression of STAT3-regulated antiapoptotic (Bcl-2, Bcl-xL, and Mcl-1), proliferative (cyclin D1), and angiogenic (VEGF) gene products; and this correlated with suppression of proliferation, the accumulation of cells in sub-G(1) phase of cell cycle, and induction of apoptosis. Overall, these results suggest that GS is a novel blocker of STAT3 activation and thus may have a potential in regulation of growth and metastasis of tumor cells.
z-Guggulsterone, a constituent of Ayurvedic medicinal plant Commiphora mukul, inhibits angiogenesis in vitro and in vivo. Molecular cancer therapeutics 2008 jan
Abstract
Our previous studies have shown that z-guggulsterone, a constituent of Indian Ayurvedic medicinal plant Commiphora mukul, inhibits the growth of human prostate cancer cells by causing apoptosis. We now report a novel response to z-guggulsterone involving the inhibition of angiogenesis in vitro and in vivo. The z-guggulsterone treatment inhibited capillary-like tube formation (in vitro neovascularization) by human umbilical vein endothelial cells (HUVEC) and migration by HUVEC and DU145 human prostate cancer cells in a concentration- and time-dependent manner. The z- and E-isomers of guggulsterone seemed equipotent as inhibitors of HUVEC tube formation. The z-guggulsterone-mediated inhibition of angiogenesis in vitro correlated with the suppression of secretion of proangiogenic growth factors [e.g., vascular endothelial growth factor (VEGF) and granulocyte colony-stimulating factor], down-regulation of VEGF receptor 2 (VEGF-R2) protein level, and inactivation of Akt. The z-guggulsterone-mediated suppression of DU145 cell migration was increased by knockdown of VEGF-R2 protein level. Ectopic expression of constitutively active Akt in DU145 cells conferred protection against z-guggulsterone-mediated inhibition of cell migration. Oral gavage of 1 mg z-guggulsterone/d (five times/wk) to male nude mice inhibited in vivo angiogenesis in DU145-Matrigel plug assay as evidenced by a statistically significant decrease in tumor burden, microvessel area (staining for angiogenic markers factor VIII and CD31), and VEGF-R2 protein expression. In conclusion, the present study reveals that z-guggulsterone inhibits angiogenesis by suppressing the VEGF-VEGF-R2-Akt signaling axis. Together, our results provide compelling rationale for further preclinical and clinical investigation of z-guggulsterone for its efficacy against prostate cancer.
更多信息
| Molecular Weight | 312.5 g/mol |
|---|---|
| Cas Number | 39025-23-5 |
| Chemical Formula | C₂₁H₂₈O₂ |
| Purity | ≥ 98% |
| Target | FXR |
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