Pseudolaric acid b inhibits angiogenesis and reduces hypoxia-inducible factor 1 alpha by promoting proteasome-mediated degradation
文献类型：期刊论文
| 作者 | Li, MH; Miao, ZH; Tan, WF; Yue, JM; Chao, Z; Lin, LP; Zhang, XW; Jian, D |
| 刊名 | Clinical cancer research
 |
| 出版日期 | 2004-12-15 |
| 卷号 | 10期号:24页码:8266-8274 |
| ISSN号 | 1078-0432 |
| 通讯作者 | Jian, d() |
| 英文摘要 | Purpose: pseudolaric acid b (pab), the naturally occurring diterpenoid isolated from the root bark of pseudolarix kaempferi gordon tree (pinaceae), possesses potent antifungal and pregnancy-terminating effects that may be tightly associated with angiogenesis. this study was to examine its angiogenic inhibition, impact on vascular endothelial growth factor (vegf) secretion from tumor cells and the possible mechanism of action. experimental design: angiogenesis inhibition was assessed by the human umbilical vascular endothelial cell proliferation, migration, and tube-formation assays, as well as the chorioallantoic membrane assay. elisa, reverse transcription-pcr, and western blotting analyses were performed to examine vegf protein secretion, mrna expression, and the possible mechanism in hypoxic mda-mb-468 cells. results: pab displayed potent in vitro antiangiogenic activity shown by inhibiting vegf-stimulated proliferation and migration and fetal bovine serum-stimulated tube formation of human umbilical vascular endothelial cells in a concentration-dependent manner. moreover, pab (10 nmol per egg) significantly suppressed in vivo angiogenesis in the chorioallantoic membrane assay. on the other hand, pab abrogated hypoxia-induced vegf secretion from mda-mb-468 cells via reducing hif-1alpha protein. additional analyses using ly294002 and u0126 indicated that the increase in hypoxia-inducible factor 1 (hif-1)alpha protein level was highly dependent on phosphatidylinositol 3'-kinase and p42/p44 mitogen-activated protein kinase activities in hypoxic mda-mb-468 cells. however, pab treatment did not affect the active (phosphorylated) forms of akt and erk. interestingly, the selective proteasome inhibitor mg-132 completely reversed the reduction of hif-1alpha protein in the pab-treated mda-mb-468 cells. conclusions: pab displays the dual antiangiogenic activities of directly inhibiting endothelial cells and abrogating paracrine stimulation of vegf from tumor cells due to reducing hif-1alpha protein by promoting its proteasome-mediated degradation in mda-mb-468 cells, which has potential clinical relevance. |
| WOS关键词 | ENDOTHELIAL GROWTH-FACTOR ; FACTOR 1-ALPHA ; FACTOR EXPRESSION ; GENE-EXPRESSION ; CELL MIGRATION ; TUBE FORMATION ; TUMOR-GROWTH ; IN-VITRO ; TRANSCRIPTION ; PATHWAY |
| WOS研究方向 | Oncology |
| WOS类目 | Oncology |
| 语种 | 英语 |
| 出版者 | AMER ASSOC CANCER RESEARCH |
| WOS记录号 | WOS:000225957800019 |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2376785 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Jian, D |
| 作者单位 | 1.Chinese Acad Sci, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai Inst Mat Med,Shanghai Inst Biol Sci, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Div Phytochem, State Key Lab Drug Res, Shanghai Inst Mat Med,Shanghai Inst Biol Sci, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Grad Sch, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, MH,Miao, ZH,Tan, WF,et al. Pseudolaric acid b inhibits angiogenesis and reduces hypoxia-inducible factor 1 alpha by promoting proteasome-mediated degradation[J]. Clinical cancer research,2004,10(24):8266-8274. |
| APA | Li, MH.,Miao, ZH.,Tan, WF.,Yue, JM.,Chao, Z.,...&Jian, D.(2004).Pseudolaric acid b inhibits angiogenesis and reduces hypoxia-inducible factor 1 alpha by promoting proteasome-mediated degradation.Clinical cancer research,10(24),8266-8274. |
| MLA | Li, MH,et al."Pseudolaric acid b inhibits angiogenesis and reduces hypoxia-inducible factor 1 alpha by promoting proteasome-mediated degradation".Clinical cancer research 10.24(2004):8266-8274. |
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来源：中国科学院大学
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