Indigo naturalis and its component tryptanthrin exert anti-angiogenic effect by arresting cell cycle and inhibiting Akt and FAK signaling in human vascular endothelial cells

Chang, Hsin-Ning; Huang, Sheng‐Teng; Yeh, Yuan-Chieh; Wang, Hsin-Shih; Wang, Tzu‐Hao; Wu, Yijing; Pang, Jong‐Hwei S.

doi:10.1016/j.jep.2015.08.050

Cited by 41 publications

(20 citation statements)

References 34 publications

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“…Increased PTEN functionality may have direct or indirect effects on FAK, either by dephosphorylation of FAK by PTEN, or by transcriptional downregulation of FAK via the PI3K/Akt/NFĸB-axis [ 47 ], respectively. In either case, suppression of FAK activity would inhibit proliferation, migration, invasion and tube formation of vascular endothelial cells into the surrounding tissue during angiogenesis [ 48 – 50 ]. From our experiments, we conclude that PTEN function and the level of PIP3 signaling need to be tightly controlled for normal embryonic angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Fine-Tuning of Pten Localization and Phosphatase Activity Is Essential for Zebrafish Angiogenesis

2016

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The lipid- and protein phosphatase PTEN is an essential tumor suppressor that is highly conserved among all higher eukaryotes. As an antagonist of the PI3K/Akt cell survival and proliferation pathway, it exerts its most prominent function at the cell membrane, but (PIP3-independent) functions of nuclear PTEN have been discovered as well. PTEN subcellular localization is tightly controlled by its protein conformation. In the closed conformation, PTEN localizes predominantly to the cytoplasm. Opening up of the conformation of PTEN exposes N-terminal and C-terminal regions of the protein that are required for both interaction with the cell membrane and translocation to the nucleus. Lack of Pten leads to hyperbranching of the intersegmental vessels during zebrafish embryogenesis, which is rescued by expression of exogenous Pten. Here, we observed that expression of mutant PTEN with an open conformation rescued the hyperbranching phenotype in pten double homozygous embryos and suppressed the increased p-Akt levels that are characteristic for embryos lacking Pten. In addition, in pten mutant and wild type embryos alike, open conformation PTEN induced stalled intersegmental vessels, which fail to connect with the dorsal longitudinal anastomotic vessel. Functional hyperactivity of open conformation PTEN in comparison to wild type PTEN seems to result predominantly from its enhanced recruitment to the cell membrane. Enhanced recruitment of phosphatase inactive mutants to the membrane did not induce the stalled vessel phenotype nor did it rescue the hyperbranching phenotype in pten double homozygous embryos, indicating that PTEN phosphatase activity is indispensable for its regulatory function during angiogenesis. Taken together, our data suggest that PTEN phosphatase activity needs to be carefully fine-tuned for normal embryogenesis and that the control of its subcellular localization is a key mechanism in this process.

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Section: Discussionmentioning

confidence: 99%

Fine-Tuning of Pten Localization and Phosphatase Activity Is Essential for Zebrafish Angiogenesis

2016

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“…The in vitro and in vivo antiangiogenic activities were realized by targeting the vascular endothelial growth factor2 (VEGFR2)‐mediated extracellular‐regulated kinase 1/2 (ERK1/2) signaling pathway . In other studies, tryptanthrin exerted an antiangiogenic effect by inhibiting cell cycle progression and Akt and FAK signaling in human vascular endothelial cells …”

Section: Biological Activities Of Quinoline and Quinazoline Alkaloidsmentioning

confidence: 99%

“…51 In other studies, tryptanthrin exerted an antiangiogenic effect by inhibiting cell cycle progression and Akt and FAK signaling in human vascular endothelial cells. 52 Furthermore, in addition to the transporter pathway, tryptanthrin downregulated glutathione S-transferase (GST) expression, reduced GST activity, and reversed multidrug resistance (MDR) partly by modulating the GST -related pathway in the MDR response in doxorubicin-resistant MCF-7 cells. 53,54 It was well absorbed across Caco-2 monolayers and inhibited P-glycoprotein (P-gp) and multidrug resistance associated protein 2 (MRP2).…”

Section: Tryptanthrinmentioning

confidence: 99%

Biologically active quinoline and quinazoline alkaloids part II

Shang

Morris‐Natschke

Yang

et al. 2018

Medicinal Research Reviews

151

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To follow-up on our prior Part I review, this Part II review summarizes and provides updated literature on novel quinoline and quinazoline alkaloids isolated during the period of 2009-2016, together with the biological activity and the mechanisms of action of these classes of natural products. Over 200 molecules with a broad range of biological activities, including antitumor, antiparasitic and insecticidal, antibacterial and antifungal, cardioprotective, antiviral, anti-inflammatory, hepatoprotective, antioxidant, anti-asthma, antitussive, and other activities, are discussed. This survey should provide new clues or possibilities for the discovery of new and better drugs from the original naturally occurring quinoline and quinazoline alkaloids.

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“…Both its roots and leaves have been used in traditional Chinese medicine to treat bacterial infections, influenza, and hepatitis for hundreds of years [1]. Correspondingly, the leaves are the important raw material of "Qing-Dai" (Indigo naturalis) [2]. Previous chemical investigations of I. tinctoria have shown a wide range of natural products, including alkaloids [3][4][5][6], lignans [7,8], flavonoids [9], ceramides [10], and organic acids [11,12].…”

Section: Introductionmentioning

confidence: 99%

Alkaloid Enantiomers from Isatis tinctoria with Neuroprotective Effects against H2O2-Induced SH-SY5Y Cell Injury

Lou

Hou

et al. 2019

Planta Med

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Six pairs of alkaloid enantiomers including 11 new alkaloids (1a/1b–5a/5b, 6a) were isolated from the leaves of Isatis tinctoria. Their structures were established by extensive spectroscopic analyses. Enantiomers were separated successfully by chiral chromatographic column and the absolute configurations of all isolates were determined by comparison of experimental and calculated electronic circular dichroism spectra. The isolated alkaloids were evaluated for their neuroprotective activities against H2O2-induced cell injury in human neuroblastoma SH-SY5Y cells. The results showed that 5a/5b and 6a/6b exhibited potent neuroprotective activities at 50 µM compared with the H2O2-treated group.

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Indigo naturalis and its component tryptanthrin exert anti-angiogenic effect by arresting cell cycle and inhibiting Akt and FAK signaling in human vascular endothelial cells

Cited by 41 publications

References 34 publications

Fine-Tuning of Pten Localization and Phosphatase Activity Is Essential for Zebrafish Angiogenesis

Fine-Tuning of Pten Localization and Phosphatase Activity Is Essential for Zebrafish Angiogenesis

Biologically active quinoline and quinazoline alkaloids part II

Alkaloid Enantiomers from Isatis tinctoria with Neuroprotective Effects against H2O2-Induced SH-SY5Y Cell Injury

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