PMID- 31706845
OWN - NLM
STAT- MEDLINE
DCOM- 20200727
LR  - 20200727
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 171
DP  - 2020 Jan
TI  - AGS-30, an andrographolide derivative, suppresses tumor angiogenesis and growth 
      in vitro and in vivo.
PG  - 113694
LID - S0006-2952(19)30393-4 [pii]
LID - 10.1016/j.bcp.2019.113694 [doi]
AB  - Poor 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.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Li, Jingjing
AU  - Li J
AD  - Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, 
      China.
FAU - Li, Feng
AU  - Li F
AD  - School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, China.
FAU - Tang, Fan
AU  - Tang F
AD  - State Key Laboratory of Quality Research in Chinese Medicine and Institute of 
      Chinese Medical Sciences, University of Macau, Macao.
FAU - Zhang, Jinming
AU  - Zhang J
AD  - College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 
      China.
FAU - Li, Renkai
AU  - Li R
AD  - Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, 
      China.
FAU - Sheng, Dekuan
AU  - Sheng D
AD  - School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, China.
FAU - Lee, Simon Ming-Yuen
AU  - Lee SM
AD  - State Key Laboratory of Quality Research in Chinese Medicine and Institute of 
      Chinese Medical Sciences, University of Macau, Macao. Electronic address: 
      simonlee@umac.mo.
FAU - Zhou, Guo-Chun
AU  - Zhou GC
AD  - School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, China. 
      Electronic address: gczhou@njtech.edu.cn.
FAU - Leung, George Pak-Heng
AU  - Leung GP
AD  - Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, 
      China. Electronic address: gphleung@hku.hk.
LA  - eng
PT  - Journal Article
DEP - 20191109
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Diterpenes)
RN  - 410105JHGR (andrographolide)
SB  - IM
MH  - Angiogenesis Inhibitors/chemistry/*pharmacology
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Cells, Cultured
MH  - Diterpenes/chemistry/*pharmacology
MH  - Embryo, Nonmammalian/blood supply/*drug effects/embryology
MH  - HT29 Cells
MH  - Human Umbilical Vein Endothelial Cells/*drug effects/metabolism
MH  - Humans
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Nude
MH  - Molecular Structure
MH  - Neovascularization, Pathologic/*prevention & control
MH  - Rats, Sprague-Dawley
MH  - Xenograft Model Antitumor Assays/methods
MH  - Zebrafish/*embryology/genetics
OTO - NOTNLM
OT  - Andrographolide derivative
OT  - Anti-angiogenic
OT  - Colon cancer
OT  - VEGF
EDAT- 2019/11/11 06:00
MHDA- 2020/07/28 06:00
CRDT- 2019/11/11 06:00
PHST- 2019/09/30 00:00 [received]
PHST- 2019/11/04 00:00 [accepted]
PHST- 2019/11/11 06:00 [pubmed]
PHST- 2020/07/28 06:00 [medline]
PHST- 2019/11/11 06:00 [entrez]
AID - S0006-2952(19)30393-4 [pii]
AID - 10.1016/j.bcp.2019.113694 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2020 Jan;171:113694. doi: 10.1016/j.bcp.2019.113694. Epub 2019 
      Nov 9.