15, 16-Dihydrotanshinone I Inhibits Hemangiomas through Inducing Pro-apoptotic and Anti-angiogenic Mechanisms in Vitro and in Vivo

doi:10.3389/fphar.2018.00025

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	15, 16-Dihydrotanshinone I Inhibits Hemangiomas through Inducing Pro-apoptotic and Anti-angiogenic Mechanisms in Vitro and in Vivo
	Cai, Yihong 2,3; Lv, Fan 2,3; Kaldybayeva, Nurshat 1,4; Zhamilya, Abilova 1,4; Wu, Zhixiang 2,3; Wu, Yeming 2,3
刊名	FRONTIERS IN PHARMACOLOGY
	2018-01-30
卷号	9
关键词	infantile hemangiomas 15,16-dihydrotanshinone I propranolol apoptosis anti-angiogenesis
ISSN号	1663-9812
DOI	10.3389/fphar.2018.00025
文献子类	Article
英文摘要	Infantile hemangioma (IH) is a common and benign vascular neoplasms, which has a high incidence in children. Although IH is benign, some patients experience complications such as pain, functional impairment, and permanent disfigurement. Treatment options for IH include corticosteroids, surgery, vincristine, interferon or cyclophosphamide. However, none of these modalities are ideal due to restrictions or potential serious side effects. There is thus a great need to explore novel treatments for IH with less side effects. Angiogenesis, vasculogenesis and tumorigenesis are the main features of IH. Tanshen is mostly used in Chinese traditional medicine to treat hematological abnormalities. Therefore, the aim of our study was to evaluate antiproliferation and anti-angiogenesis effects on hemangiomas cells by extracted Tanshen compounds compared with propranolol, the first-line treatment for IH currently, both in vitro and in vivo. Cell viability, apoptosis, protein expression and anti-angiogenesis were analyzed by CCK8, Annexin V staining, Western blot and tube formation, respectively. The anti-tumor activity in vivo was evaluated using a mouse xenograft model. Fourteen major compounds extracting from Tanshen were screened for their ability to inhibit hemangiomas cells. Of the 14 compounds investigated, 15,16-Dihydrotanshinone I (DHTS) was the most potent modulator of EOMA cell biology. DHTS could significantly decrease EOMA cells proliferation by inducing cell apoptosis, which is much more efficient than propranolol in vitro. DHTS increased the expression of several apoptosis-related proteins, including caspase9, caspase3, PARP, AIF, BAX, cytochrome c, caspase8 and FADD and significantly inhibited angiogenesis, as indicated by reduced tube formation and diminished expression of vascular endothelial cell growth factor receptor 2 and matrix metalloproteinase 9. In nude mice xenograft experiment, DHTS (10 mg/kg) could significantly inhibit the tumor growth of EOMA cells as well as propranolol (40 mg/kg). Our study showed that DHTS was much more effective than propranolol in inhibiting hemangiomas proliferation and angiogenesis in vitro and in vivo, which could have potential therapeutic applications for treatment of IH.
资助项目	Natural Science Foundation of China[81402478] ; Natural Science Foundation of China[81572918] ; Shanghai Rising-Star Program[16QA1402900]
WOS关键词	INFANTILE HEMANGIOMAS ; 15,16-DIHYDROTANSHINONE I ; DEPENDENT APOPTOSIS ; CANCER CELLS ; PROPRANOLOL ; GROWTH ; MODEL ; ACTIVATION ; EXPRESSION ; MANAGEMENT
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000423545600001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279942]
专题	新药研究国家重点实验室中科院受体结构与功能重点实验室
通讯作者	Wu, Zhixiang; Wu, Yeming
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Nat Prod Chem Dept, Shanghai, Peoples R China 2.Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Dept Pediat Surg, Shanghai, Peoples R China; 3.Shanghai Inst Pediat Res, Div Pediat Oncol, Shanghai, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China;
推荐引用方式 GB/T 7714	Cai, Yihong,Lv, Fan,Kaldybayeva, Nurshat,et al. 15, 16-Dihydrotanshinone I Inhibits Hemangiomas through Inducing Pro-apoptotic and Anti-angiogenic Mechanisms in Vitro and in Vivo[J]. FRONTIERS IN PHARMACOLOGY,2018,9.
APA	Cai, Yihong,Lv, Fan,Kaldybayeva, Nurshat,Zhamilya, Abilova,Wu, Zhixiang,&Wu, Yeming.(2018).15, 16-Dihydrotanshinone I Inhibits Hemangiomas through Inducing Pro-apoptotic and Anti-angiogenic Mechanisms in Vitro and in Vivo.FRONTIERS IN PHARMACOLOGY,9.
MLA	Cai, Yihong,et al."15, 16-Dihydrotanshinone I Inhibits Hemangiomas through Inducing Pro-apoptotic and Anti-angiogenic Mechanisms in Vitro and in Vivo".FRONTIERS IN PHARMACOLOGY 9(2018).