Suramin is a Potent Inhibitor of Vascular Endothelial Growth Factor. A Contribution to the Molecular Basis of its Antiangiogenic Action

Waltenberger, Johannes; Mayr, Ulrike Beate; Frank, Hedwig; Hombach, Vinzenz

doi:10.1006/jmcc.1996.0142

Cited by 84 publications

(43 citation statements)

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“…It can interfere with almost all cellular processes, such as differentiation, proliferation, migration, and apoptosis (Zaniboni 1990;Foekens et al 1992;Takano et al 1994;Yokoyama et al 1997;Gills and Windebank 1998;Reynolds et al 1998). At the molecular level, it has been found to block the action of several growth factors and signaling molecules (Hosang 1985;Adams et al 1991;Vincent et al 1996;Waltenberger et al 1996;Mancini et al 1999;Botta et al 2000), to block P2 receptors (von Kugelgen and Wetter 2000), and to block several intra-and extracellular enzymes (Moroz 1977;Marjomaki and Salminen 1986;Nakajima et al 1991;Bojanowski et al 1992;Meijer 1995;Zhang et al 1998;Slusher et al 2000). Given the pleiotropic action of suramin, it will be difficult to identify exactly the cellular and molecular mechanisms underlying the teratogenic effects observed in the present study.…”

Section: Teratogenic Mechanisms Of Suraminmentioning

confidence: 96%

Teratogenic effects of suramin on the chick embryo

et al. 2003

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Suramin, a polysulfonated naphthylamine, has been used for the chemotherapy of trypanosomiasis and onchocerciasis since about the 1920s. Currently, it is also being tested as an anticancer agent. It is hoped that suramin might stop the progression of some kinds of cancer since it has been found to inhibit the proliferation and migration of cells and the formation of new blood vessels. These processes are not only essential for the development and progression of cancer, but also for normal embryonic development. Suramin might, therefore, be a potent teratogen. In the literature, however, we have found only scant information on this subject. In the present study, we demonstrate the teratogenic effects of suramin on chick embryos. Suramin was injected into the coelomic cavity of chick embryos on incubation day (ID) 3. Following reincubation until ID 8, suramin-treated embryos ( n=50) were examined for congenital malformations and compared with a control group ( n=30). The survival rate of suramin-treated embryos was markedly reduced compared with controls (50% vs 90%). Among the 25 survivors the following malformations were recorded: caudal dysgenesia (100%), median facial clefts with hypertelorism (92%), malformations of the aortic arch arteries (88%), hypo-/aplasia of the allantoic vesicle (84%), microphthalmia (52%), abnormalities of the great arterial trunks (44%), unilateral or bilateral cleft lips (40%), heart defects with juxtaposition of the right atrial appendage (36%), persistence of the lens vesicle (32%), median clefts of the lower beak (8%), omphalocele (4%), and cloacal exstrophy (4%). These results show that suramin is a potent teratogen. The possible implications of our findings for human beings and the possible teratogenic mechanisms of suramin are discussed. Use of suramin in experimental teratology might help to clarify the morphogenesis of median facial clefts and of some congenital heart defects.

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Section: Teratogenic Mechanisms Of Suraminmentioning

confidence: 96%

Teratogenic effects of suramin on the chick embryo

et al. 2003

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“…[51][52][53] Suramin interacts with VEGFR2 and is a potent VEGF antagonist. 54 In vitro, suramin inhibited multiple control points of angiogenesis, including endothelial cell migration, proliferation, and proteolytic activities. 55 In vivo, suramin inhibited angiogenesis in a number of experimental models, including the chick chorioallantoic membrane (CAM) assay, the rat corneal and rat aortic ring assays, and gelatin sponges loaded with bFGF and implanted subcutaneously in mice.…”

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confidence: 99%

Anti‐angiogenic drugs: from bench to clinical trials

Quesada

Muñoz‐Chápuli

Medina

2006

Medicinal Research Reviews

143

126

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Angiogenesis, the generation of new capillaries through a process of pre-existing microvessel sprouting, is under stringent control and normally occurs only during embryonic and post-embryonic development, reproductive cycle, and wound repair. However, in many pathological conditions (solid tumor progression, metastasis, diabetic retinopathy, hemangioma, arthritis, psoriasis and atherosclerosis among others), the disease appears to be associated with persistent upregulated angiogenesis. The development of specific anti-angiogenic agents arises as an attractive therapeutic approach for the treatment of cancer and other angiogenesis-dependent diseases. The formation of new blood vessels is a complex multi-step process. Endothelial cells resting in the parent vessels are activated by an angiogenic signal and stimulated to synthesize and release degradative enzymes allowing endothelial cells to migrate, proliferate and finally differentiate to give rise to capillary tubules. Any of these steps may be a potential target for pharmacological intervention. In spite of the disappointing results obtained initially in clinical trials with anti-angiogenic drugs, recent reports with positive results in phases II and III trials encourage expectations in their therapeutic potential. This review discusses the current approaches for the discovery of new compounds that inhibit angiogenesis, with emphasis on the clinical developmental status of anti-angiogenic drugs.

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“…12 Chemically it is a polysulphonated napthyl urea and has been used long since for the treatment of trypanosomiasis. It is a potent inhibitor of PDGF, IGF, bFGF 13,14 and VEGF, 15 which also brings it in focus as an antiangiogenic compound. 16 On account of its antiproliferative effects, it has been used for treatment of various malignant cancers.…”

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Suramin augments the antitumor and antimetastatic activity of pentoxifylline in B16F10 melanoma

Dua

Ingle

Gude

2007

Intl Journal of Cancer

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Rapid tumor growth and metastasis are 2 major problems associated with treatment of malignant melanoma. Therefore, drugs that can intervene these processes are of clinical importance. Pentoxifylline (PTX), a methyl xanthine derivative, has been shown to inhibit B16F10 melanoma tumor growth and metastasis. We hypothesized that suramin when combined with PTX enhances its antineoplastic effects, which we have examined using the B16F10 mouse melanoma model. Suramin in simultaneous or sequential combination potentiated the cytotoxic effects of PTX on B16F10 cells. PTX arrested cells in the G0-G1 phase and suramin augmented the effects. Both the drugs inhibited F10 adhesion to laminin, matrigel and collagen type IV and showed enhanced inhibition in combination The combination also demonstrated significantly higher inhibition in cell motility (p 5 0.002) and invasion through matrigel (p 5 0.005) as compared to the single agents. Suramin synergized with PTX in its effects on secretion of MMP-9 gelatinase. DBA2/J mice implanted with intradermal B16F10 tumor were used as a model to study tumor growth. Animals were intratumorally treated with 50 mg/kg of PTX, 10 mg/kg of suramin and their combinations. Simultaneous administration of the drugs inhibited tumor growth by 5-to 6-folds. Tumor growth was completely blocked in sequential regimen with regression in some cases. The number and size of metastatic nodules on lung was also reduced significantly by the combination treatment. In conclusion, the novel combination of PTX and suramin has synergistic antitumor and antimetastatic activity in B16F10 melanoma and may be a promising approach in treatment of patients suffering from malignant melanoma. ' 2007 Wiley-Liss, Inc.Key words: pentoxifylline; suramin; B16F10 melanoma; metastasis; combination therapy Malignant melanoma is the deadliest form of skin cancer, and its incidence has shown a 6-fold increase since the past 2 to 3 decades.1 There is no standard treatment for patients with metastatic melanoma. Treatment options include the surgical resection of isolated metastases, therapy with dacarbazine, and immunotherapy. However, response rates associated with these measures range between 15 and 20%, and hence there is an urgent need for the development of new therapies. The success of antimetastatic therapy depends on inhibition of diverse stimuli produced by the tumor and its microenvironment while limiting overall toxicity. Thus it has been suggested that a combination of antimetastatic compounds may be more effective than monotherapies.In our earlier reports we have demonstrated that pentoxifylline (PTX), a methyl xanthine derivative inhibits B16F10 melanoma solid tumor growth and metastasis to lung, 3 which is mediated via its inhibitory action on cell adhesion, MMP-9 and -2 secretion, 4 and tumor angiogenesis.5 PTX has been used to enhance tumor sensitivity to both radiation 6 and alkylating agents 7 because of its antioxidant nature and its property to abrogate the G2-M checkpoint, respectively. It has also been reporte...

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Suramin is a Potent Inhibitor of Vascular Endothelial Growth Factor. A Contribution to the Molecular Basis of its Antiangiogenic Action

Cited by 84 publications

References 0 publications

Teratogenic effects of suramin on the chick embryo

Teratogenic effects of suramin on the chick embryo

Anti‐angiogenic drugs: from bench to clinical trials

Suramin augments the antitumor and antimetastatic activity of pentoxifylline in B16F10 melanoma

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