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Article: Dietary compound glycyrrhetinic acid suppresses tumor angiogenesis and growth by modulating antiangiogenic and proapoptotic pathways in vitro and in vivo

TitleDietary compound glycyrrhetinic acid suppresses tumor angiogenesis and growth by modulating antiangiogenic and proapoptotic pathways in vitro and in vivo
Authors
KeywordsDietary compound
Antiangiogenesis
Apoptosis
Glycyrrhetinic acid
Ovarian cancer
Issue Date2020
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/jnutbio
Citation
The Journal of Nutritional Biochemistry, 2020, v. 77, p. article no. 108268 How to Cite?
AbstractGlycyrrhetinic 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.
Persistent Identifierhttp://hdl.handle.net/10722/281236
ISSN
2019 Impact Factor: 4.873
2015 SCImago Journal Rankings: 1.886

 

DC FieldValueLanguage
dc.contributor.authorLI, J-
dc.contributor.authorTang, F-
dc.contributor.authorLI, R-
dc.contributor.authorChen, Z-
dc.contributor.authorLee, SM-Y-
dc.contributor.authorFu, C-
dc.contributor.authorZhang, J-
dc.contributor.authorLeung, GP-H-
dc.date.accessioned2020-03-09T09:51:58Z-
dc.date.available2020-03-09T09:51:58Z-
dc.date.issued2020-
dc.identifier.citationThe Journal of Nutritional Biochemistry, 2020, v. 77, p. article no. 108268-
dc.identifier.issn0955-2863-
dc.identifier.urihttp://hdl.handle.net/10722/281236-
dc.description.abstractGlycyrrhetinic 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.-
dc.languageeng-
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/jnutbio-
dc.relation.ispartofThe Journal of Nutritional Biochemistry-
dc.subjectDietary compound-
dc.subjectAntiangiogenesis-
dc.subjectApoptosis-
dc.subjectGlycyrrhetinic acid-
dc.subjectOvarian cancer-
dc.titleDietary compound glycyrrhetinic acid suppresses tumor angiogenesis and growth by modulating antiangiogenic and proapoptotic pathways in vitro and in vivo-
dc.typeArticle-
dc.identifier.emailLeung, GP-H: gphleung@hkucc.hku.hk-
dc.identifier.authorityLeung, GP-H=rp00234-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.jnutbio.2019.108268-
dc.identifier.pmid31830590-
dc.identifier.scopuseid_2-s2.0-85076048791-
dc.identifier.hkuros309353-
dc.identifier.volume77-
dc.identifier.spagearticle no. 108268-
dc.identifier.epagearticle no. 108268-
dc.publisher.placeUnited States-

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