Rhapontigenin Inhibited Hypoxia Inducible Factor 1 Alpha Accumulation and Angiogenesis in Hypoxic PC-3 Prostate Cancer Cells
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概要
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Hypoxia inducible factor 1 alpha (HIF-1α) is frequently over-expressed in the numerous types of cancer and plays an important role in angiogenesis. In the present study, the inhibitory mechanism of rhapontigenin isolated from Vitis coignetiae was investigated on HIF-1α stability and angiogenesis in human prostate cancer PC-3 cells. Rhapontigenin significantly suppressed HIF-1α accumulation at protein level but not at mRNA level in PC-3 cells under hypoxia. Also, rhapontigenin suppressed hypoxia-induced HIF-1α activation in various cancer cells, such as colorectal adenocarcinoma (SW620), breast adenocarcinoma (MCF-7), fibrosarcoma (HT-1080) and prostate carcinoma (LNCaP). Interestingly, rhapontigenin had more potency in inhibition of hypoxia-induced HIF-1α expression than that of resveratrol, a known HIF-1α inhibitor. In addition, rhapontigenin promoted hypoxia-induced HIF-1α degradation and cycloheximide (CHX) blocked protein synthesis. A prolyl hydroxylase (PHD) inhibitor dimethyloxalylglycine (DMOG) is usually utilized to examine whether prolyl hydroxylation is involved in inhibition of HIF-1α accumulation. Here, DMOG recovered HIF-1α accumulation inhibited by rhapontigenin. Immunoprecipitation assay also revealed that rhapotigenin enhanced the binding of hydroxylated HIF-1α to von Hippel-Lindau (VHL) tumor suppressor protein. Furthermore, rhapontigenin reduced vascular endothelial growth factor (VEGF) secretion in hypoxic PC-3 cells as well as suppressed tube formation in human umbilical vein endothelial cells (HUVECs) treated by the conditioned media of hypoxic PC-3 cells. However, anti-angiogenic effect of rhapontigenin in hypoxic PC-3 cells was reversed by DMOG. Taken together, these findings suggest that rhapontigenin inhibits HIF-1α accumulation and angiogenesis in PC-3 prostate cancer cells.
- 公益社団法人 日本薬学会の論文
著者
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Kim Young
College of Pharmacy, Chungnam National University
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KIM Sung-Hoon
College of Oriental Medicine, Kyunghee University
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Jeong Soo-Jin
College of Oriental Medicine, Kyung Hee University
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Lee Hyo-Jung
College of Oriental Medicine, Kyung Hee University
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Lee Hyo-Jeong
College of Oriental Medicine, Kyung Hee University
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Lee Hong-beom
Division Of Ocean Science Korea Maritime University
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Lee Eun-Ok
College of Oriental Medicine, Kyung Hee University
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Chen Chang-Yan
Beth Israel Deaconess Medical Center, Harvard Medical School
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Lee Hyo-jung
Coll. Of Oriental Medicine Kyung Hee Univ.
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Jung Deok-Beom
College of Oriental Medicine, Kyung Hee University
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Kim Young
College Of Pharmacy And Research Institute Of Pharmaceutical Science Seoul National University
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Ahn Kyoo
College of Oriental Medicine, Kyung Hee University
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Kim Sung-Hoon
College of Oriental Medicine, Kyung Hee University
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Kim Young
Colledge of Pharmacy, Wonkwang University
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