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Article: AGS-30, an andrographolide derivative, suppresses tumor angiogenesis and growth in vitro and in vivo

TitleAGS-30, an andrographolide derivative, suppresses tumor angiogenesis and growth in vitro and in vivo
Authors
KeywordsAndrographolide derivative
Anti-angiogenic
Colon cancer
VEGF
Issue Date2020
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/biochempharm
Citation
Biochemical Pharmacology, 2020, v. 171, p. article no. 113694 How to Cite?
AbstractPoor bioavailability and limited efficacy are challenges associated with using andrographolide as a therapeutic agent. We recently synthesized AGS-30, a new andrographolide derivative, in our laboratory. In this study we investigated the potential anti-tumor effect of AGS-30 and the underlying mechanisms, particularly those related to angiogenesis. Results from our in vitro experiments showed that AGS-30 exerted anti-angiogenic effects by inhibiting endothelial cell proliferation, migration, invasion, and tube formation. Phosphorylation and activation of angiogenesis-related signaling molecules (e.g., vascular endothelial growth factor [VEGF] receptor 2, mitogen-activated protein kinase kinase 1/2, extracellular signal-regulated kinase 1/2, mechanistic target of rapamycin [mTOR], protein kinase B [Akt], and p38) were markedly reduced by AGS-30. Meanwhile, AGS-30 potently inhibited cell proliferation and phosphorylation of cell survival-related proteins (e.g., Akt, mTOR, and ERK1/2) and decreased the expression of VEGF in HT-29 colon cancer cells. AGS-30 blocked microvessel sprouting in a rat aortic ring model and blood vessel formation in zebrafish embryos and a mouse Matrigel plug model. Additionally, AGS-30 suppressed tumor growth and angiogenesis in HT-29 colon cancer cell xenografts in nude mice. These effects were not observed when same concentration of andrographolide, the parent compound of AGS-30, was used. Thus, AGS-30 exerted a strong antitumor effect by inhibiting tumor cell growth and angiogenesis and is a candidate compound for the treatment of cancer.
DescriptionLink to Free access
Persistent Identifierhttp://hdl.handle.net/10722/281237
ISSN
2017 Impact Factor: 4.235
2015 SCImago Journal Rankings: 2.263

 

DC FieldValueLanguage
dc.contributor.authorLI, J-
dc.contributor.authorLi, F-
dc.contributor.authorTang, F-
dc.contributor.authorZhang, J-
dc.contributor.authorLI, R-
dc.contributor.authorSheng, D-
dc.contributor.authorLee, SM-Y-
dc.contributor.authorZhou, G-C-
dc.contributor.authorLeung, GP-H-
dc.date.accessioned2020-03-09T09:51:58Z-
dc.date.available2020-03-09T09:51:58Z-
dc.date.issued2020-
dc.identifier.citationBiochemical Pharmacology, 2020, v. 171, p. article no. 113694-
dc.identifier.issn0006-2952-
dc.identifier.urihttp://hdl.handle.net/10722/281237-
dc.descriptionLink to Free access-
dc.description.abstractPoor bioavailability and limited efficacy are challenges associated with using andrographolide as a therapeutic agent. We recently synthesized AGS-30, a new andrographolide derivative, in our laboratory. In this study we investigated the potential anti-tumor effect of AGS-30 and the underlying mechanisms, particularly those related to angiogenesis. Results from our in vitro experiments showed that AGS-30 exerted anti-angiogenic effects by inhibiting endothelial cell proliferation, migration, invasion, and tube formation. Phosphorylation and activation of angiogenesis-related signaling molecules (e.g., vascular endothelial growth factor [VEGF] receptor 2, mitogen-activated protein kinase kinase 1/2, extracellular signal-regulated kinase 1/2, mechanistic target of rapamycin [mTOR], protein kinase B [Akt], and p38) were markedly reduced by AGS-30. Meanwhile, AGS-30 potently inhibited cell proliferation and phosphorylation of cell survival-related proteins (e.g., Akt, mTOR, and ERK1/2) and decreased the expression of VEGF in HT-29 colon cancer cells. AGS-30 blocked microvessel sprouting in a rat aortic ring model and blood vessel formation in zebrafish embryos and a mouse Matrigel plug model. Additionally, AGS-30 suppressed tumor growth and angiogenesis in HT-29 colon cancer cell xenografts in nude mice. These effects were not observed when same concentration of andrographolide, the parent compound of AGS-30, was used. Thus, AGS-30 exerted a strong antitumor effect by inhibiting tumor cell growth and angiogenesis and is a candidate compound for the treatment of cancer.-
dc.languageeng-
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/biochempharm-
dc.relation.ispartofBiochemical Pharmacology-
dc.subjectAndrographolide derivative-
dc.subjectAnti-angiogenic-
dc.subjectColon cancer-
dc.subjectVEGF-
dc.titleAGS-30, an andrographolide derivative, suppresses tumor angiogenesis and growth 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.bcp.2019.113694-
dc.identifier.pmid31706845-
dc.identifier.scopuseid_2-s2.0-85075380530-
dc.identifier.hkuros309354-
dc.identifier.volume171-
dc.identifier.spagearticle no. 113694-
dc.identifier.epagearticle no. 113694-
dc.publisher.placeUnited States-

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