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Dietary compound glycyrrhetinic acid suppresses tumor angiogenesis and growth by modulating antiangiogenic and proapoptotic pathways in vitro and in vivo
Li,Jingjing1,2; Tang,Fan3; Li,Renkai2; Chen,Zhejie1; Lee,Simon Ming Yuen3; Fu,Chaomei1; Zhang,Jinming1; Leung,George Pak Heng2
2020-03-01
Source PublicationJournal of Nutritional Biochemistry
ISSN0955-2863
Volume77
Abstract

Glycyrrhetinic acid (GA) is a major bioactive compound of licorice. The objective of this study was to investigate the effects of GA on ovarian cancer, particularly those related to angiogenesis and apoptosis, and to elucidate the underlying mechanisms of action. In vitro studies showed that GA significantly inhibited proliferation, migration, invasion and tube formation in human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner. GA inhibited the phosphorylation of major receptors and enzymes involved in angiogenesis, such as VEGFR2, mTOR, Akt, ERK1/2, MEK1/2, p38 and JNK1/2 in HUVECs. In addition, GA induced apoptosis, loss of mitochondrial membrane potential and cell cycle arrest in G1 phase in A2780 ovarian cancer cells. The proapoptotic effect of GA involved the increased phosphorylation of p38 and JNK1/2; increased cleavage of caspase 3, caspase 9 and PARP; reduced phosphorylation of mTOR, Akt and ERK1/2; and reduced expressions of survivin and cyclin D1. Ex vivo studies showed that GA significantly inhibited microvessel sprouting in rat aortic ring model. In vivo studies showed that GA inhibited the formation of new blood vessels in zebrafish and mouse Matrigel plug. GA also significantly reduced the size of ovarian cancer xenograft tumors in nude mice. Taken together, GA possesses potential antitumor effects, and the underlying mechanisms may involve the inhibition of signaling pathways related to angiogenesis and the activation of apoptotic pathways in cancer cells. Our findings suggest that GA could serve as an effective regimen in the prevention or treatment of cancer.

KeywordAntiangiogenesis Apoptosis Dietary Compound Glycyrrhetinic Acid Ovarian Cancer
DOI10.1016/j.jnutbio.2019.108268
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaBiochemistry & Molecular Biology ; Nutrition & Dietetics
WOS SubjectBiochemistry & Molecular Biology ; Nutrition & Dietetics
WOS IDWOS:000516883200006
Scopus ID2-s2.0-85076048791
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Cited Times [WOS]:6   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorZhang,Jinming; Leung,George Pak Heng
Affiliation1.College of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu,China
2.Department of Pharmacology and Pharmacy,The University of Hong Kong,Hong Kong
3.State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences,University of Macau,Macao,Macao
Recommended Citation
GB/T 7714
Li,Jingjing,Tang,Fan,Li,Renkai,et al. Dietary compound glycyrrhetinic acid suppresses tumor angiogenesis and growth by modulating antiangiogenic and proapoptotic pathways in vitro and in vivo[J]. Journal of Nutritional Biochemistry,2020,77.
APA Li,Jingjing,Tang,Fan,Li,Renkai,Chen,Zhejie,Lee,Simon Ming Yuen,Fu,Chaomei,Zhang,Jinming,&Leung,George Pak Heng.(2020).Dietary compound glycyrrhetinic acid suppresses tumor angiogenesis and growth by modulating antiangiogenic and proapoptotic pathways in vitro and in vivo.Journal of Nutritional Biochemistry,77.
MLA Li,Jingjing,et al."Dietary compound glycyrrhetinic acid suppresses tumor angiogenesis and growth by modulating antiangiogenic and proapoptotic pathways in vitro and in vivo".Journal of Nutritional Biochemistry 77(2020).
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