莱菔硫烷诱导线粒体裂变抑制血管生成

doi:10.16689/j.cnki.cn11-9349/r.2020.01.011

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Abstract Objective To investigate the effect of Sulforaphane (SFN) on angiogenesis and the underlying mechanism. Methods The primary human umbilical vein endothelial cells (HUVECs) were used as the study model in vitro, with 1‰ DMSO incubation as control group. WST-1 kit was used to detect the proliferative activity of HUVECs after exposed to 5～100μmol/L SFN for 24h. The effects of SFN on angiogenesis were further examined by the tube formation assay and transwell migration assay after 10μmol/L treatment. Mito-Tracker Green FM dye-labeled mitochondria were captured by confocal microscopy imaging technology, and Western blot was applied to detect the expression level of mitochondrial dynamics related proteins, including mitofusin-1/2 (Mfn1/2) and dynamin-related protein 1 (Drp1), as well as vascular endothelial growth factor (VEGF) in HUVECs after 10μmol/L SFN intervention for 24h. Results SFN significantly inhibited the proliferative activity of HUVECs after intervention for 24h at concentrations higher than 5μmol/L with the IC50 38.15μmol/L. The inhibition rates were 17.82% (P=0.009), 35.33%(P<0.001), 65.29%(P<0.001), 66.82% (P<0.001) and 68.05% (P<0.001), respectively, at concentrations of 10, 20, 40, 80, and 100μmol/L. Compared to control, the migration rate of HUVECs in the 10μmol/L SFN-treated group was reduced by 42.98% (P=0.018), and the formation capacity of the capillary-like structure quantified by the number of meshes, the number of nodes, and the total length, were reduced by 83.94% (P=0.011), 59.22% (P=0.021) and 50.49% (P=0.025), respectively. Mechanistically, analysis of mitochondrial morphology and mitochondrial dynamics related protein expression showed that 10μmol/L SFN significantly promoted mitochondrial fission with the number of mitochondrial networks and the aspect ratio significantly decreased by 27.39% (P=0.006) and 11.37% (P<0.001), whereas circularity significantly increased by 11.97% (P<0.001). In line with mitochondrial morphology alteration, SFN at 10μmol/L significantly induced the protein expression of Drp1 (1.71 folds) (P<0.001), while surpressed that of Mfn1/2 59.30% (P=0.006) and 74.75% (P=0.031) of control, accompanied by VEGF protein expression downregulation (65.66% of control) (P=0.003). Conclusion SFN possesses the anti-angiogenic activity and the potential mechanism may involve promotion of mitochondrial fission in vascular endothelial cell.

Key words： Sulforaphane Angiogenesis Mitochondrial fission

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	Articles by authors
	Wang Yaqian
	Zheng Xiangyu
	Chen Fangfang
	Li Dan

Cite this article:

Wang Yaqian,Zheng Xiangyu,Chen Fangfang, et al. Sulforaphane inhibits angiogenesis via induction of mitochondrial fission[J]. Electron J Metab Nutr Cancer, 2020, 7(1): 57-63.

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http://182.92.200.144/EN/10.16689/j.cnki.cn11-9349/r.2020.01.011 OR http://182.92.200.144/EN/Y2020/V7/I1/57

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