Flavonoids inhibit hypoxia-induced vascular endothelial growth factor expression by a HIF-1 independent mechanism

Ansó, Elena; Zuazo, Alicia; Irigoyen, Marta; Urdaci, María C.; Rouzaut, Ana; Martinez–Irujo, Juan J.

doi:10.1016/j.bcp.2010.02.004

Cited by 72 publications

(54 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the present study, quercetin inhibited hypoxia-induced VEGF, which was in accord with the study of Anso et al (25). When cells were exposed to hypoxia in the presence of this flavonoid, HIF-1a translocated to the nucleus and interacted with p300/CBP, but this complex was transcriptionally inactive.…”

Section: Discussionsupporting

confidence: 93%

Pulmonary prophylactic impact of melatonin and/or quercetin: A novel therapy for inflammatory hypoxic stress in rats

et al. 2017

View full text Add to dashboard Cite

The study aims to compare, through histological and biochemical studies, the effects of quercetin, melatonin and their combination in regulation of immuno-inflammatory mediators and heat shock protein expressions in sodium nitrite induced hypoxia in rat lungs. The results revealed that NaNO 2 injection caused a significant decrease in Hb in rats, while serum levels of TNF-a, IL-6 and CRP, VEGF and HSP70 were elevated compared to the control group. Administration of melatonin, quercetin or their combination before NaNO 2 injection markedly reduced these parameters. Histopathological examination of the lung tissue supported these biochemical findings. The study suggests that melatonin and/or quercetin are responsible for lung tissue protection in hypoxia by downregulation of immuno-inflammatory mediators and heat shock protein expressions. Pre-treatment of hypoxic animals with a combination of melatonin and quercetin was effective in modulating most of the studied parameters to near-normal levels.

show abstract

Section: Discussionsupporting

confidence: 93%

Pulmonary prophylactic impact of melatonin and/or quercetin: A novel therapy for inflammatory hypoxic stress in rats

et al. 2017

View full text Add to dashboard Cite

show abstract

“…However, the other flavonoid (DTFG) produced no suppression of the growth of the cancer cell, which suggested chemical group may impact the activation of flavonoid compound. The results of accumulated researches showed that the presence of an additional hydroxyl group at 4 0 of the B ring or 5 of A ring was important for antitumor activity of flavonoids (Anso et al, 2010;Lopez-posadas et al, 2008), which was also found in our research work. Accordingly, it was suggested that potential antitumor effects can be similarly revealed in other cancer cell lines.…”

Section: Discussionsupporting

confidence: 85%

A flavonoid compound fromChrysosplenium nudicauleinhibits growth and induces apoptosis of the human stomach cancer cell line SGC-7901

Luo

Yang

et al. 2015

Pharmaceutical Biology

View full text Add to dashboard Cite

Context: Gastric cancer remains highly prevalent, but treatment options are limited. Natural products have proved to be a rich source of anticancer drugs. Chrysosplenium nudicaule Ledeb. (Saxifragaceae) is a perennial herb that grows in the highlands of China. It has been used as a traditional Chinese medicine to treat digestive diseases for hundreds of years. Recent studies revealed that this herb had anticancer activity, and the flavonoids were speculated to be the effective components. 6,7,3 0 -Trimethoxy-3,5,4 0 -trihydroxy flavone (TTF) and 5,4 0 -dihydroxy-3,6,3 0 trimethoxy-flavone-7-O-b-D-glucoside (DTFG) are flavonoid compounds isolated from Chrysosplenium nudicaule. Objective: This study examined the effect of TTF and DTFG on SGC-7901 human stomach cancer cell in vitro to determine the anticancer and induction of apoptosis properties of TTF. Materials and methods: The proliferation of cells treated with 32, 16, 8, 4, and 2 lg/mL of TTF or DTFG for 24, 48, and 72 h was assessed by the MTT assay. After being treated with TTF, the apoptosis of SGC-7901 cells was assessed by acridine orange staining, ultrastructure, electrophoresis of DNA fragmentation, and flow cytometry. Results: Results indicated that TTF inhibited the growth of cancer cells with an IC 50 value of 8.33 lg/mL after 72 h incubation. However, DTFG showed no inhibitory effect on the growth of the cancer cell. Further studies on TTF also confirmed that it was able to induce apoptosis of SGC-7901 cells at a concentration as low as 4 lg/mL. Discussion and conclusion: The apoptotic effect of TTF makes it a promising candidate for future chemotherapeutic application in treating stomach cancer.

show abstract

“…19,20 Luteolin inhibits hypoxia-induced VEGF expression by a HIF-1 independent mechanism, suppression of STAT3 tyrosine phosphorylation. 21 In the present study, we demonstrated that luteolin effectively inhibited in vitro angiogenesis in HRMECs and retinal neovascularization in OIR without toxicity, which would be related to that luteolin effectively inhibited VEGF expression via HIF-1a dependent mechanism by blockade of ROS production, and VEGF-induced angiogenesis via regulating possibly VEGFR2 signaling pathway. Taken together, our results suggest that this anti-angiogenic activity of luteolin as an antioxidant could be applied to variable vasoproliferative retinopathies induced by ischemia as well as ROP.…”

Section: Discussionmentioning

confidence: 77%

Anti-Angiogenic Effect of Luteolin on Retinal Neovascularization via Blockade of Reactive Oxygen Species Production

Park

Cho

Jun

et al. 2012

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PURPOSE. Oxidative stress-induced vascular endothelial growth factor (VEGF) is thought to play a critical role in the pathogenesis of retinopathy of prematurity (ROP). This study was performed to investigate the anti-angiogenic effect of luteolin against reactive oxygen species (ROS)-induced retinal neovascularization.METHODS. The toxicity of luteolin was evaluated through modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in human retinal microvascular endothelial cells (HRMECs) as well as TUNEL staining in the retina of C57BL/6J mice. After intravitreal injection of luteolin in the mouse model of ROP, retinal neovascularization was examined by fluorescence angiography and vessel counting. Anti-angiogenic activity of luteolin was evaluated by VEGF-induced migration and tube formation assay. The effect of luteolin on tertiarybutylhydroperoxide (t-BH)-induced ROS production was measured with 2 0 7 0 -dichlorofluorescein diacetate. The effect of luteolin on t-BH-induced and hypoxia-induced VEGF transcription and expression were evaluated by RT-PCR and Western blot, respectively. RESULTS.Luteolin never affected the viability of HRMECs up to 10 lM, where luteolin never induced any structural change in all retinal layers. Luteolin inhibited retinal neovascularization in the mouse model of ROP. Moreover, VEGF-induced migration and tube formation were significantly decreased by cotreatment of luteolin. Luteolin attenuated VEGF transcription via blockade of t-BH-induced ROS production. Luteolin suppressed hypoxia-induced VEGF expression via attenuating hypoxia inducible factor 1 a expression. CONCLUSIONS.Our results suggest that luteolin could be a potent anti-angiogenic agent for retinal neovascularization, which is related to anti-oxidative activity to block ROS production and to subsequently suppress VEGF expression and the proangiogenic effect of VEGF. (Invest Ophthalmol Vis Sci. 2012; 53:7718-7726)

show abstract

Flavonoids inhibit hypoxia-induced vascular endothelial growth factor expression by a HIF-1 independent mechanism

Cited by 72 publications

References 40 publications

Pulmonary prophylactic impact of melatonin and/or quercetin: A novel therapy for inflammatory hypoxic stress in rats

Pulmonary prophylactic impact of melatonin and/or quercetin: A novel therapy for inflammatory hypoxic stress in rats

A flavonoid compound fromChrysosplenium nudicauleinhibits growth and induces apoptosis of the human stomach cancer cell line SGC-7901

Anti-Angiogenic Effect of Luteolin on Retinal Neovascularization via Blockade of Reactive Oxygen Species Production

Contact Info

Product

Resources

About