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姜黄素通过下调MCL-1和HIF-1α诱导婴儿血管瘤内皮细胞凋亡并抑制其增殖。

Curcumin induces apoptosis and inhibits proliferation in infantile hemangioma endothelial cells via downregulation of MCL-1 and HIF-1α.

作者信息

Lou Suhui, Wang Yanfang, Yu Zujiang, Guan Kelei, Kan Quancheng

机构信息

Department of Pharmacology Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.

出版信息

Medicine (Baltimore). 2018 Feb;97(7):e9562. doi: 10.1097/MD.0000000000009562.

DOI:10.1097/MD.0000000000009562
PMID:29443732
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5839849/
Abstract

BACKGROUND

Curcumin has been used as an alternative medicine for the treatment of infantile hemangiomas (IHs); however, the mechanism underlying the effectiveness of curcumin in IHs remains largely unclear.

METHODS

In this study, we isolated primary human hemangioma endothelial cells (HemECs) from fresh surgical specimens of 3 patients. We treated HemECs by curcumin and investigated the alterations in proliferative and apoptotic signaling pathways with cell counting kit-8, flow cytometry, western blotting, immunofluorescence, and real-time polymerase chain reaction.

RESULTS AND CONCLUSION

We found that curcumin potently inhibited proliferation in HemECs, achieving low-micromolar IC50 (the half maximal inhibitory concentration) value. We also observed that treatment with curcumin induced apoptosis in HemECs, as evidenced by positively Annexin-V-FITC staining, caspase-3 activation, and cleavage of poly(adenosine diphosphate-ribose) polymerase (PARP) in the treated cells. Moreover, we showed that curcumin suppressed the expression of antiapoptotic protein myeloid cell leukemia-1 (MCL-1), hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF).Altogether, our study suggests that the effectiveness of curcumin in IHs may be associated with its potent antiproliferative and apoptotic activities in HemECs.

摘要

背景

姜黄素已被用作治疗婴儿血管瘤(IHs)的替代药物;然而,姜黄素治疗IHs有效性的潜在机制仍不清楚。

方法

在本研究中,我们从3例患者的新鲜手术标本中分离出原代人血管瘤内皮细胞(HemECs)。我们用姜黄素处理HemECs,并通过细胞计数试剂盒-8、流式细胞术、蛋白质免疫印迹法、免疫荧光法和实时聚合酶链反应研究增殖和凋亡信号通路的变化。

结果与结论

我们发现姜黄素能有效抑制HemECs的增殖,达到低微摩尔IC50(半数最大抑制浓度)值。我们还观察到姜黄素处理诱导HemECs凋亡,处理后的细胞中膜联蛋白-V-异硫氰酸荧光素阳性染色、半胱天冬酶-3激活和聚(二磷酸腺苷-核糖)聚合酶(PARP)裂解证明了这一点。此外,我们表明姜黄素抑制抗凋亡蛋白髓样细胞白血病-1(MCL-1)、缺氧诱导因子1α(HIF-1α)和血管内皮生长因子(VEGF)的表达。总之,我们的研究表明姜黄素治疗IHs的有效性可能与其对HemECs的强大抗增殖和凋亡活性有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdb5/5839849/93d1b737de53/medi-97-e9562-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdb5/5839849/ecb80233f2f7/medi-97-e9562-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdb5/5839849/8ba802e05923/medi-97-e9562-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdb5/5839849/d2f06d44351f/medi-97-e9562-g004.jpg
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