Chloroquine Used in Combination with Chemotherapy Synergistically Suppresses Growth and Angiogenesis <i>In Vitro</i> and <i>In Vivo</i>

Gürel-Gürevin, Ebru; Kıyan, Hülya Tuba; Esener, Osman Behzat Burak; Aydınlık, Şeyma; Uvez, Ayca; Ulukaya, Engin; Dimas, Konstantinos; Armutak, Elif Ilkay

doi:10.21873/anticanres.12689

Cited by 20 publications

(17 citation statements)

References 36 publications

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“…Interestingly, anti-angiogenic treatments are frequently seen in literature involve the use of chemical substances, such as the chemotherapy drug doxorubicin [ 129 , 165 ] as well as thalidomide derivatives [ 59 ]. The application of nanoparticles such as gold [ 60 , 84 ], green [ 166 ], zinc tungstate [ 61 ] and chitosan derived nanoparticles [ 94 ] have high efficacy in the inhibition of blood vessel development, with significant reductions in blood vessel number, length and density reported.…”

Section: Cam Experimental Treatmentsmentioning

confidence: 99%

Microvascular Experimentation in the Chick Chorioallantoic Membrane as a Model for Screening Angiogenic Agents including from Gene-Modified Cells

Kennedy

Coen

Wheatley

et al. 2021

IJMS

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The chick chorioallantoic membrane (CAM) assay model of angiogenesis has been highlighted as a relatively quick, low cost and effective model for the study of pro-angiogenic and anti-angiogenic factors. The chick CAM is a highly vascularised extraembryonic membrane which functions for gas exchange, nutrient exchange and waste removal for the growing chick embryo. It is beneficial as it can function as a treatment screening tool, which bridges the gap between cell based in vitro studies and in vivo animal experimentation. In this review, we explore the benefits and drawbacks of the CAM assay to study microcirculation, by the investigation of each distinct stage of the CAM assay procedure, including cultivation techniques, treatment applications and methods of determining an angiogenic response using this assay. We detail the angiogenic effect of treatments, including drugs, metabolites, genes and cells used in conjunction with the CAM assay, while also highlighting the testing of genetically modified cells. We also present a detailed exploration of the advantages and limitations of different CAM analysis techniques, including visual assessment, histological and molecular analysis along with vascular casting methods and live blood flow observations.

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Section: Cam Experimental Treatmentsmentioning

confidence: 99%

Microvascular Experimentation in the Chick Chorioallantoic Membrane as a Model for Screening Angiogenic Agents including from Gene-Modified Cells

Kennedy

Coen

Wheatley

et al. 2021

IJMS

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“…This fact can favor the action of doxorubicin, since its mechanisms of action are the intercalation of DNA and inhibition of topoisomerase [38]. In addition, doxorubicin was reported to induce cytotoxicity and disrupt tube-like structures formed by human umbilical vein endothelial cells (HUVECs) as well as reduce migration, cell proliferation, and angiogenesis, according to the CAM assay [70]. Additionally, Magnelli et al described the antiangiogenic properties of alpha-bisabolol through the induction of apoptosis and inhibition of the formation of tube-like structures by HUVECs cells in vitro [71].…”

Section: Discussionmentioning

confidence: 99%

Nanoformulation Shows Cytotoxicity against Glioblastoma Cell Lines and Antiangiogenic Activity in Chicken Chorioallantoic Membrane

et al. 2021

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Glioblastoma (GB) is a histological and genetically heterogeneous brain tumor that is highly proliferative and vascularized. The prognosis is poor with currently available treatment. In this study, we evaluated the cytotoxicity and antiangiogenic activity of doxorubicin-loaded-chitosan-coated-arginylglycylaspartic acid-functionalized-poly(ε-caprolactone)-alpha bisabolol-LNC (AB-DOX-LNC-L-C-RGD). The nanoformulation was prepared by self-assembling followed by interfacial reactions, physicochemically characterized and evaluated in vitro against GB cell lines (U87MG and U138MG) and in vivo using the chicken chorioallantoic membrane assay (CAM). Spherical shape nanocapsules had a hydrodynamic mean diameter of 138 nm, zeta potential of +13.4 mV, doxorubicin encapsulation of 65%, and RGD conjugation of 92%. After 24 h of treatment (U87MG and U138MG), the median inhibition concentrations (IC50) were 520 and 490 nmol L−1 doxorubicin-equivalent concentrations, respectively. The treatment induced antiproliferative activity with S-phase cell-cycle arrest and apoptosis in the GB cells. Furthermore, after 48 h of exposure, evaluation of antiangiogenic activity (CAM) showed that the relative vessel growth following treatment with the nanocapsules was 5.4 times lower than that with the control treatment. The results support the therapeutic potential of the nanoformulation against GB and, thereby, pave the way for future preclinical studies.

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“…Recent studies have shown that autophagic responses can be triggered in vascular endothelial cells by a variety of antiangiogenic agents [28]. Although some antiangiogenic agents have been demonstrated to induce autophagic cell death in vascular endothelial cells, it is suggested that in most situations, induction of autophagy exerts cytoprotective effects on vascular endothelial cells, and this acts as an important cellular mechanism of drug resistance [28][29][30]. For instance, the antiangiogenic agent sulforaphane (SUL) induces both autophagy and apoptosis in HUVECs.…”

Section: Discussionmentioning

confidence: 99%

Monocarbonyl curcumin analog A2 potently inhibits angiogenesis by inducing ROS-dependent endothelial cell death

et al. 2019

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Excessive and abnormal vessel growth plays a critical role in the pathogenesis of many diseases, such as cancer. Angiogenesis is one of the hallmarks of cancer growth, invasion, and metastasis. Discovery of novel antiangiogenic agents would provide new insights into the mechanisms of angiogenesis, as well as potential drugs for cancer treatment. In the present study, we investigated the antiangiogenic activity of a series of monocarbonyl analogs of curcumin synthesized previously in our lab. We found that curcumin analog A2 displayed the full potential to be developed as a novel antiangiogenic agent. Curcumin analog A2 at and above 20 μM dramatically inhibited the migration and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro, new microvessels sprouting from the rat aortic rings ex vivo and newly formed microvessels in chicken chorioallantoic membranes (CAMs) and Matrigel plus in vivo. We further demonstrated that curcumin analog A2 exerted its antiangiogenic activity mainly through inducing endothelial cell death via elevating NADH/NADPH oxidase-derived ROS. Curcumin analog A2 at the antiangiogenic concentrations also triggered autophagy in HUVECs, but this process is neither a prerequisite for toxicity, leading to the cell death nor a protective response against the toxicity of curcumin analog A2. In conclusion, we demonstrate for the first time the potent antiangiogenic activity of the monocarbonyl curcumin analog A2, which could serve as a promising potential therapeutic agent for the prevention and treatment angiogenesis-related diseases, such as cancer.

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Chloroquine Used in Combination with Chemotherapy Synergistically Suppresses Growth and Angiogenesis In Vitro and In Vivo

Abstract: Chloroquine enhanced the anti-angiogenic effect of doxorubicin on CAM at the tested concentrations.

Cited by 20 publications

References 36 publications

Microvascular Experimentation in the Chick Chorioallantoic Membrane as a Model for Screening Angiogenic Agents including from Gene-Modified Cells

Microvascular Experimentation in the Chick Chorioallantoic Membrane as a Model for Screening Angiogenic Agents including from Gene-Modified Cells

Nanoformulation Shows Cytotoxicity against Glioblastoma Cell Lines and Antiangiogenic Activity in Chicken Chorioallantoic Membrane

Monocarbonyl curcumin analog A2 potently inhibits angiogenesis by inducing ROS-dependent endothelial cell death

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