The anti-angiogenic effect and novel mechanisms of action of Combretastatin A-4

Su, Min; Huang, Jingjia; Liu, Suyou; Xiao, Yuhang; Qin, Xiyuan; Liu, Jia; Pi, Chaoqiong; Luo, Tiao; Li, Jijia; Chen, Xianghui; Luo, Zhitian

doi:10.1038/srep28139

Cited by 66 publications

(61 citation statements)

References 32 publications

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“…Thereafter, the supernatant was aspirated and replaced with 110 μL of DMSO and shaked for 15 min to dissolve the formazan crystals produced by viable cells. Hundred microliters of the supernatant was transferred into a new 96‐well plate and the absorbance was measured at 570 nm by using a microplate reader (BioTek; Su et al, ; Zamani et al, ).…”

Section: Methodsmentioning

confidence: 99%

Additively manufactured small‐diameter vascular grafts with improved tissue healing using a novel SNAP impregnation method

et al. 2019

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The vascular network has a complex architecture such as branches, curvatures, and bifurcations which is even more complicated in view of individual patients' defect anatomy requiring custom‐specifically designed vascular implants. In this work, 3D printing is used to overcome these challenges and a new shorter impregnation method was developed to incorporate S‐nitroso‐N‐acetyl‐d‐penicillamine (SNAP) as a nitric oxide (NO) donor to printed grafts. The 3D‐printed small‐diameter vascular grafts (SDVGs) were impregnated with SNAP solution during SNAP synthesis (S1) or with SNAP dissolved in methanol (S2). The advantage of the newly developed S1 impregnation method is the elimination of the synthesis step by direct impregnation inside the S1 solution. Scanning electron microscopy imaging reveals the successful crystal formation in both methods. The results demonstrate that both S1‐ and S2‐impregnated grafts, after covering with polycaprolactone topcoat, can release NO in a controlled manner and in the physiological range (0.5–4.0 × 10−10 mol cm−2 min−1) over a 15 days period. The created grafts with a NO‐releasing surface have also shown bactericidal effect while the healing properties of the implant were improved by promoting migration and proliferation of endothelial cells (ECs). These results suggest that incorporation of 3D printing technology with the newly developed S1 impregnation of SNAP can optimize and shorten the manufacturing process of the next generation of patient‐based antibacterial SDVGs with a higher attraction for ECs.

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Section: Methodsmentioning

confidence: 99%

Additively manufactured small‐diameter vascular grafts with improved tissue healing using a novel SNAP impregnation method

et al. 2019

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“…Thus, bevacizumab (Avastin; Genentech, South San Francisco, CA), a monoclonal antibody against VEGF, promotes vascular normalization and, when combined with other cytotoxic agents, shows significant improvement in antitumor efficacy (Miller et al, 2007). Combretastatin, a vascular disrupting agent that targets the tumor vessel endothelium, inhibits VEGF and VEGF receptor 2, resulting in a more normal vessel phenotype (Su et al, 2016). Although promising agents have been identified, the clinical results with these agents have not been as impressive as those obtained in preclinical studies.…”

Section: Introductionmentioning

confidence: 99%

Sepiapterin Enhances Tumor Radio- and Chemosensitivities by Promoting Vascular Normalization

Rabender

Bruno

Alam

et al. 2018

J Pharmacol Exp Ther

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Previously, we demonstrated that nitric oxide (NO) synthase (NOS) is uncoupled in a wide range of solid tumors and that restoring NOS coupling with the tetrahydrobiopterin precursor sepiapterin (SP) inhibits tumor progression. Endothelial dysfunction characterizes the poorly functional vasculature of solid tumors, and since NO is critical for regulation of endothelial function we asked whether SP, by recoupling NOS, improves tumor vasculature structure and function-enhancing chemotherapeutic delivery and response to radiotherapy. MMTV-neu mice with spontaneous breast tumors were treated with SP by oral gavage and evaluated by multispectral optoacoustic tomographic analysis of tumor HbO and by tissue staining for markers of hypoxia, blood perfusion, and markers of endothelial and smooth muscle proteins. Recoupling tumor NOS activity results in vascular normalization observed as reduced tumor hypoxia, improved tumor percentage of HbO and perfusion, as well as increased pericyte coverage of tumor blood vessels. The normalized vasculature and improved tumor oxygenation led to a greater than 2-fold increase in radiation-induced apoptosis compared with radiation or SP alone. High-performance liquid chromatography analysis of tumor doxorubicin levels showed a greater than 50% increase in doxorubicin uptake and a synergistic effect on tumor cell apoptosis. This study highlights for the first time the importance of NOS uncoupling and endothelial dysfunction in the development of tumor vasculature and presents a new approach for improving the tumoricidal efficacies of chemotherapy and radiotherapy.

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“…Thus, we were able to study the direct effects of the 4HNE and also the effect of ALDH2 inhibition by DSF. The process of angiogenesis is carried out by several sequential steps including the proliferation of ECs, degradation of extracellular matrix, migration, and finally the organization of ECs to form capillary‐like structures . All these steps are regulated by the intricate balance between proangiogenic and antiangiogenic factors.…”

Section: Discussionmentioning

confidence: 99%

Aldehyde dehydrogenase 2 inhibition potentiates 4‐hydroxy‐2‐nonenal induced decrease in angiogenesis of coronary endothelial cells

Roy

Palaniyandi

2020

Cell Biochemistry & Function

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Coronary endothelial cell (EC) dysfunction including defective angiogenesis is reported in cardiac diseases. 4-Hydroxynonenal (4HNE) is a lipid peroxidation product, which is increased in cardiac diseases and implicated in cellular toxicity. Aldehyde dehydrogenase (ALDH) 2 is a mitochondrial enzyme that metabolizes 4HNE and reduces 4HNE-mediated cytotoxicity. Thus, we hypothesize that ALDH2 inhibition potentiates 4HNE-mediated decrease in coronary EC angiogenesis in vitro. To test our hypothesis, first, we treated the cultured mouse coronary EC (MCEC) lines with 4HNE (25, 50, and 75 μM) for 2 and 4 hours. Next, we pharmacologically inhibited ALDH2 by disulfiram (DSF) (2.5 μM) before challenging the cells with 4HNE. In this study, we found that 4HNE attenuated tube formation which indicates decreased angiogenesis. Next, we found that 4HNE has significantly downregulated the expressions of vascular endothelial growth factor receptor (VEGFR) 2 (P < .05 for mRNA and P = .005 for protein), Sirtuin 1 (SIRT 1) (P < 0.0005 for mRNA), and Ets-related gene (ERG) (P < 0.0001 for mRNA and P < 0.005 for protein) in MCECs compared with control. ALDH 2 inhibition by DSF potentiated 4HNE-induced decrease in angiogenesis (P < 0.05 vs 4HNE at 2 h and P < 0.0005 vs 4HNE at 4 h) by decreasing the expressions of VEGFR2 (P < 0.005 for both mRNA and protein), SIRT 1 (P < 0.05), and ERG (P < 0.005) relative to 4HNE alone. Thus, we conclude that ALDH2 acts as a proangiogenic signaling molecule by alleviating the antiangiogenic effects of 4HNE in MCECs. KEYWORDSaldehyde dehydrogenase 2, angiogenesis, coronary endothelial cells, ERG, 4-hydroxy-2-nonenal,

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The anti-angiogenic effect and novel mechanisms of action of Combretastatin A-4

Cited by 66 publications

References 32 publications

Additively manufactured small‐diameter vascular grafts with improved tissue healing using a novel SNAP impregnation method

Additively manufactured small‐diameter vascular grafts with improved tissue healing using a novel SNAP impregnation method

Sepiapterin Enhances Tumor Radio- and Chemosensitivities by Promoting Vascular Normalization

Aldehyde dehydrogenase 2 inhibition potentiates 4‐hydroxy‐2‐nonenal induced decrease in angiogenesis of coronary endothelial cells

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