The Experts below are selected from a list of 810 Experts worldwide ranked by ideXlab platform
Michael Weller - One of the best experts on this subject based on the ideXlab platform.
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n 3 4 dimethoxycinnamoyl anthranilic acid Tranilast inhibits transforming growth factor β release and reduces migration and invasiveness of human malignant glioma cells
International Journal of Cancer, 2001Co-Authors: Michael Platten, Christine Wildbode, Wolfgang Wick, Jens Leitlein, J Dichgans, Michael WellerAbstract:Extensive infiltration of normal brain tissue and suppression of anti-tumor immune surveillance mediated by molecules such as transforming growth factor-β (TGF-β) are key biological features that contribute to the malignant phenotype of human gliomas. Tranilast (N-[3,4-dimethoxycinnamoyl]-anthranilic acid) is an anti-allergic compound used clinically to control atopic and fibrotic disorders. These effects are attributed to the suppression of TGF-β1 synthesis and interference with growth factor–mediated proliferation and migration of fibroblasts and vascular smooth muscle cells. Here, we show that Tranilast inhibits DNA synthesis and proliferation of human malignant glioma cells and promotes p21 accumulation in the absence of cytotoxicity. Further, Tranilast reduces the release of TGF-β1 and TGF-β2 by glioma cells and inhibits migration, chemotactic responses and invasiveness. These effects are not associated with a reduction of αvβ3 integrin expression at the cell surface but appear to involve inhibition of matrix metalloproteinase-2 expression and activity. Neither the Tranilast-mediated inhibition of proliferation nor the inhibition of migration was counteracted by supplementation with exogenous TGF-β. Finally, Tranilast administered orally inhibited the growth of experimental 9L rat gliomas and reduced expression of TGF-β2in vivo. We conclude that Tranilast might be a useful therapeutic agent for the treatment of human malignant glioma because of a TGF-β-independent abrogation of the malignant phenotype of proliferation, migration and invasiveness and because of the antagonism of TGF-β-associated immunosuppression. © 2001 Wiley-Liss, Inc.
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n 3 4 dimethoxycinnamoyl anthranilic acid Tranilast inhibits transforming growth factor beta relesase and reduces migration and invasiveness of human malignant glioma cells
International Journal of Cancer, 2001Co-Authors: Michael Platten, Christine Wildbode, Wolfgang Wick, Jens Leitlein, J Dichgans, Michael WellerAbstract:Extensive infiltration of normal brain tissue and suppression of anti-tumor immune surveillance mediated by molecules such as transforming growth factor-beta (TGF-beta) are key biological features that contribute to the malignant phenotype of human gliomas. Tranilast (N-[3,4-dimethoxycinnamoyl]-anthranilic acid) is an anti-allergic compound used clinically to control atopic and fibrotic disorders. These effects are attributed to the suppression of TGF-beta1 synthesis and interference with growth factor-mediated proliferation and migration of fibroblasts and vascular smooth muscle cells. Here, we show that Tranilast inhibits DNA synthesis and proliferation of human malignant glioma cells and promotes p21 accumulation in the absence of cytotoxicity. Further, Tranilast reduces the release of TGF-beta1 and TGF-beta2 by glioma cells and inhibits migration, chemotactic responses and invasiveness. These effects are not associated with a reduction of alpha(v)beta(3) integrin expression at the cell surface but appear to involve inhibition of matrix metalloproteinase-2 expression and activity. Neither the Tranilast-mediated inhibition of proliferation nor the inhibition of migration was counteracted by supplementation with exogenous TGF-beta. Finally, Tranilast administered orally inhibited the growth of experimental 9L rat gliomas and reduced expression of TGF-beta2 in vivo. We conclude that Tranilast might be a useful therapeutic agent for the treatment of human malignant glioma because of a TGF-beta-independent abrogation of the malignant phenotype of proliferation, migration and invasiveness and because of the antagonism of TGF-beta-associated immunosuppression.
Richard E Gilbert - One of the best experts on this subject based on the ideXlab platform.
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early and delayed Tranilast treatment reduces pathological fibrosis following myocardial infarction
Heart Lung and Circulation, 2013Co-Authors: Fiona See, Richard E Gilbert, Masataka Watanabe, Andrew R Kompa, Bing Hui Wang, Andrew J Boyle, Darren J Kelly, Henry KrumAbstract:Background Tranilast has been shown to inhibit TGFβ1-related fibrosis and organ failure in various disease models. We sought to examine the effects of Tranilast on left ventricular (LV) remodelling post-MI. Methods Following coronary artery ligation, Sprague Dawley rats were randomised to receive Tranilast (300mg/kg/d, p.o.) or vehicle control over one of two treatment periods: (1) from 24h until seven days post-MI, (2) from seven days to 28 days post-MI. Cardiac tissue was harvested for molecular, immunohistochemical and cell culture analyses. Results Tranilast treatment of MI rats from 24h until seven days post-MI reduced myocardial collagen content, α1 (I) procollagen, TGFβ1 and CTGF mRNA transcripts, monocyte/macrophage infiltration and exacerbated infarct expansion compared with vehicle-treatment. Delaying the commencement of Tranilast treatment to seven days post-MI attenuated myocardial fibrosis, gene expression of α1(I) procollagen, α1(III) procollagen, fibronectin, TGFβ1 and CTGF mRNA transcripts, and monocyte/macrophage infiltration at 28d compared to vehicle-treatment, without detriment to infarct healing. Extended post-MI also preserved LV infarct size. In cultures of rat cardiac fibroblasts, Tranilast attenuated TGFβ1-stimulated fibrogenesis. Conclusion Tranilast inhibits myocardial TGFβ1 expression, fibrosis in rat post-MI and collagen production in cardiac fibroblasts. While Tranilast intervention from 24h post-MI exacerbated infarct expansion, delaying the commencement of treatment to seven days post-MI impeded LV remodelling.
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Tranilast attenuates diastolic dysfunction and structural injury in experimental diabetic cardiomyopathy
American Journal of Physiology-heart and Circulatory Physiology, 2007Co-Authors: Darren J Kelly, Henry Krum, Jennifer H Martin, Yuan Zhang, Kim A Connelly, Alison J Cox, Richard E GilbertAbstract:Diastolic dysfunction is an increasingly recognized complication of diabetes that develops in relatively young patients as a result of diabetic cardiomyopathy (DCM). With recent advances in echocardiographic technology now permitting the reliable assessment of diastolic function in the rat, we examined cardiac function and structure in diabetic rodents and assessed the effects of intervening with Tranilast, an antifibrotic compound that has been shown to attenuate the actions of transforming growth factor-beta (TGF-beta) in cardiac fibroblasts. We also sought to examine the mechanism whereby Tranilast inhibits the actions of TGF-beta. Six-week-old heterozygous (mRen-2)27 rats were randomized to receive either streptozotocin or citrate buffer and then further randomized to receive either Tranilast (400 mg x kg(-1) x day(-1) by twice daily gavage) or vehicle for another 8 wk. Cell signaling was examined in neonatal cardiac fibroblasts. After 8 wk, diabetic rats showed evidence of impaired diastolic function with reduced early-to-late atrial wave ratio and prolonged deceleration time in association with fibrosis, apoptosis, and hypertrophy (all P < 0.05). Treatment with Tranilast prevented the development of diastolic dysfunction and the histopathological features of DCM. While Tranilast did not affect Smad phosphorylation, it significantly attenuated TGF-beta-induced p44/42 mitogen-activated protein kinase phosphorylation.
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combination therapy with Tranilast and angiotensin converting enzyme inhibition provides additional renoprotection in the remnant kidney model
Kidney International, 2006Co-Authors: Darren J Kelly, Richard E Gilbert, Yuan Zhang, Alison J CoxAbstract:Despite current therapy with agents that block the renin-angiotensin system, renal dysfunction continues to progress in a significant proportion of patients with kidney disease. Several pre-clinical studies have reported beneficial effects of Tranilast, an inhibitor of transforming growth factor (TGF)-beta's actions in a range of diseases that are characterized by fibrosis. However, whether such therapy provides additional benefits in renal disease, when added to angiotensin-converting enzyme (ACE) inhibition, has not been explored. We randomized subtotally (5/6) nephrectomized rats to receive vehicle, the ACE inhibitor, perindopril (6 mg/l), Tranilast (400 mg/kg/day), or their combination for 12 weeks. When compared with sham-nephrectomized animals, subtotally nephrectomized animals had reduced creatinine clearance, proteinuria, glomerulosclerosis, interstitial fibrosis, tubular atrophy, and evidence of TGF-beta activity, as indicated by the abundant nuclear staining of phosphorylated Smad2. These manifestations of injury and TGF-beta activation were all attenuated by treatment with either Tranilast or perindopril, with the latter also attenuating the animals' hypertension. When compared with single-agent treatment, the combination of Tranilast and perindopril provided additional, incremental improvements in creatinine clearance, proteinuria, and glomerulosclerosis, and a reduction in nuclear phsopho-Smad2 beyond single-agent treatment. These findings indicate that the combination of Tranilast and perindopril was superior to single-agent treatment on kidney structure and function in the remnant kidney model, and suggests the potential for such dual therapy in kidney disease that continues to progress despite blockade of the renin-angiotensin system.
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Tranilast attenuates connective tissue growth factor induced extracellular matrix accumulation in renal cells
Kidney International, 2006Co-Authors: Xinming Chen, Stephen M Twigg, T S Polhill, Richard E Gilbert, Carol A PollockAbstract:Tranilast ( N -[3,4-dimethoxycinnamoyl]anthranilic acid) is a synthetic compound that we have recently reported to inhibit transforming growth factor- β 1 (TGF- β 1)-induced tubulointerstitial fibrosis in the kidney. Connective tissue growth factor (CTGF) is recognized as a potent downstream mediator of TGF- β 1. Both proximal tubule cells (PTCs) and cortical fibroblasts (CFs) are considered to be responsible for the production of tubulointerstitial extracellular matrix (ECM). These studies were undertaken to assess the profibrotic effects of CTGF in an in vitro model of the human PTCs and CFs, and to determine whether Tranilast is effective in limiting the in vitro matrix responses induced by CTGF. Primary cultures of PTCs and CFs were exposed to CTGF (20 ng/ml)±Tranilast (100 μ M). Cell hypertrophy and the secretion of the ECM proteins fibronectin and collagen IV were determined. The effects of Tranilast on TGF- β 1-induced CTGF mRNA expression and on phosphorylation of Smad2 were determined. CTGF significantly induced cell hypertrophy, increased fibronectin, and collagen IV secretion in PTCs and CFs. In all cases, the CTGF-induced increase in ECM protein was inhibited in the presence of Tranilast. Tranilast reduced CTGF mRNA and phosphorylation of Smad2, which were induced by TGF- β 1 in PTCs and CFs. These results suggest that Tranilast is a potential effective antifibrotic compound in the kidney, exerting its effects via inhibition of TGF- β 1-induced CTGF expression and downstream activation of the Smad2 pathway in both PTCs and CFs.
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Tranilast attenuates cardiac matrix deposition in experimental diabetes role of transforming growth factor beta
Cardiovascular Research, 2005Co-Authors: Jennifer H Martin, Fiona See, Darren J Kelly, Henry Krum, Allison J Cox, S A Mifsud, Yuan Zhang, Jennifer L Wilkinsonberka, Richard E GilbertAbstract:Objective : The pathological accumulation of extracellular matrix is a characteristic feature of diabetic cardiomyopathy that is directly related to a loss of function. Tranilast ( n -[3,4-anthranilic acid), used for the treatment of fibrotic skin diseases, has also been shown to inhibit transforming growth factor-β (TGF-β)-induced matrix production in kidney epithelial cells. Methods : To investigate the effects of Tranilast in the diabetic heart, we examined its effects in cultured cardiac fibroblasts and then assessed its effects in (mRen-2)27 diabetic rats with established disease (8 weeks after streptozotocin). Results : In vitro studies demonstrated a 58% reduction in TGF-β1-induced 3[H]-hydroxyproline incorporation with Tranilast 30 μM ( p <0.01). At 16 weeks, diabetes in the Ren-2 rat was associated with increased cardiac fibrosis and evidence of TGF-β1 activation, as measured by the abundance of phosphorylated Smad2. Despite persistent hyperglycaemia and hypertension, Tranilast attenuated cardiac fibrosis by 37% ( p <0.05) in association with reduction in phospho-Smad2 ( p <0.01). Conclusion : These findings indicate that Tranilast has antifibrotic actions in the Ren-2 model of experimental diabetic cardiac disease by mechanisms that might attributable to reduced TGF-β activity.
Michael Platten - One of the best experts on this subject based on the ideXlab platform.
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n 3 4 dimethoxycinnamoyl anthranilic acid Tranilast inhibits transforming growth factor β release and reduces migration and invasiveness of human malignant glioma cells
International Journal of Cancer, 2001Co-Authors: Michael Platten, Christine Wildbode, Wolfgang Wick, Jens Leitlein, J Dichgans, Michael WellerAbstract:Extensive infiltration of normal brain tissue and suppression of anti-tumor immune surveillance mediated by molecules such as transforming growth factor-β (TGF-β) are key biological features that contribute to the malignant phenotype of human gliomas. Tranilast (N-[3,4-dimethoxycinnamoyl]-anthranilic acid) is an anti-allergic compound used clinically to control atopic and fibrotic disorders. These effects are attributed to the suppression of TGF-β1 synthesis and interference with growth factor–mediated proliferation and migration of fibroblasts and vascular smooth muscle cells. Here, we show that Tranilast inhibits DNA synthesis and proliferation of human malignant glioma cells and promotes p21 accumulation in the absence of cytotoxicity. Further, Tranilast reduces the release of TGF-β1 and TGF-β2 by glioma cells and inhibits migration, chemotactic responses and invasiveness. These effects are not associated with a reduction of αvβ3 integrin expression at the cell surface but appear to involve inhibition of matrix metalloproteinase-2 expression and activity. Neither the Tranilast-mediated inhibition of proliferation nor the inhibition of migration was counteracted by supplementation with exogenous TGF-β. Finally, Tranilast administered orally inhibited the growth of experimental 9L rat gliomas and reduced expression of TGF-β2in vivo. We conclude that Tranilast might be a useful therapeutic agent for the treatment of human malignant glioma because of a TGF-β-independent abrogation of the malignant phenotype of proliferation, migration and invasiveness and because of the antagonism of TGF-β-associated immunosuppression. © 2001 Wiley-Liss, Inc.
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n 3 4 dimethoxycinnamoyl anthranilic acid Tranilast inhibits transforming growth factor beta relesase and reduces migration and invasiveness of human malignant glioma cells
International Journal of Cancer, 2001Co-Authors: Michael Platten, Christine Wildbode, Wolfgang Wick, Jens Leitlein, J Dichgans, Michael WellerAbstract:Extensive infiltration of normal brain tissue and suppression of anti-tumor immune surveillance mediated by molecules such as transforming growth factor-beta (TGF-beta) are key biological features that contribute to the malignant phenotype of human gliomas. Tranilast (N-[3,4-dimethoxycinnamoyl]-anthranilic acid) is an anti-allergic compound used clinically to control atopic and fibrotic disorders. These effects are attributed to the suppression of TGF-beta1 synthesis and interference with growth factor-mediated proliferation and migration of fibroblasts and vascular smooth muscle cells. Here, we show that Tranilast inhibits DNA synthesis and proliferation of human malignant glioma cells and promotes p21 accumulation in the absence of cytotoxicity. Further, Tranilast reduces the release of TGF-beta1 and TGF-beta2 by glioma cells and inhibits migration, chemotactic responses and invasiveness. These effects are not associated with a reduction of alpha(v)beta(3) integrin expression at the cell surface but appear to involve inhibition of matrix metalloproteinase-2 expression and activity. Neither the Tranilast-mediated inhibition of proliferation nor the inhibition of migration was counteracted by supplementation with exogenous TGF-beta. Finally, Tranilast administered orally inhibited the growth of experimental 9L rat gliomas and reduced expression of TGF-beta2 in vivo. We conclude that Tranilast might be a useful therapeutic agent for the treatment of human malignant glioma because of a TGF-beta-independent abrogation of the malignant phenotype of proliferation, migration and invasiveness and because of the antagonism of TGF-beta-associated immunosuppression.
Serge Jothy - One of the best experts on this subject based on the ideXlab platform.
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Tranilast treatment decreases cell growth migration and inhibits colony formation of human breast cancer cells
Experimental and Molecular Pathology, 2011Co-Authors: Venkateswaran Subramaniam, Gerald J Prudhomme, Serge Jothy, Olga AceAbstract:In the treatment of breast cancer, although a wide of choice of drugs and treatment modalities are available, drug resistance or drug toxicity poses a considerable challenge. Tranilast is a well tolerated drug used in the treatment of allergic disorders. Previous works in various models have shown that Tranilast has the potential to be used as an anti-cancer drug. Hence, in this study using human breast cancer cell lines BT-474 and MDA-MB-231, we studied the effect of Tranilast on cell growth, migration and ability to prevent colony formation in vitro, properties that are relevant to a possible therapeutic effect in breast cancer. We found that Tranilast inhibits the growth of both breast cancer cell lines. In the cell migration experiments, the tumor cells exhibit significantly slower wound closure after Tranilast treatment, as well as reduced migration using an insert system. Downregulation of MRTF-A, a global cytoskeleton regulator was observed after Tranilast treatment. Additionally, Tranilast treatment increased levels of cleaved PARP in both cell lines tested indicating a stimulation of apoptosis. A significant reduction in colony size and number was observed in soft agar clonogenic assays in both cell lines after Tranilast treatment. BT-474 cells were more responsive to Tranilast treatment compared to MDA-MB-231 cells, suggesting a difference in modes of action, or sensitivity, possibly related to their different receptor status. Based on these changes in cancer cell lines, we conclude that Tranilast exerts effects that set a rationale for future preclinical studies in animal models of breast cancer.
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Tranilast inhibits cell proliferation and migration and promotes apoptosis in murine breast cancer
Anti-Cancer Drugs, 2010Co-Authors: Venkateswaran Subramaniam, Rabindranath Chakrabarti, Gerald J Prudhomme, Serge JothyAbstract:The malignant transformation of breast epithelium involves a number of cellular pathways, including those dependent on signaling from TGF beta. Tranilast [N-(3, 4-dimethoxycinnamonyl)-anthranilic acid] is a drug that is used in Japan to control allergic disorders in patients, and its mechanism of action involves TGF beta. In view of the multiple roles of TGF beta in tumor progression, we hypothesized in this study that Tranilast impacts cell proliferation, apoptosis, and migration. Using the mouse breast cancer cell line 4T1, our studies showed that Tranilast increases AKT1 phosphorylation and decreases ERK1/2 phosphorylation. Alterations in the cell cycle mediators' cyclin D1, p27, cyclin A, pRB, cyclin B, and Cdc2 were observed after exposure to Tranilast, favoring cell arrest beyond the G1/S phase. Tranilast reduced tumor cell proliferation even when it was amplified by exogenous TGF beta. TGF beta-neutralizing antibody did not cause a significant decrease in cell proliferation. Tranilast treatment upregulates p53, induces PARP cleavage in vitro, consistent with a promotion of tumor cell apoptosis. TGF beta-neutralizing antibody downregulates endoglin and matrix metalloproteinases (MMP)-9 levels in vitro indicating that the Tranilast effect is mediated through TGF beta modulation. Tranilast treatment results in the inhibition of cell migration and invasion. Western blot analysis of tumor lysates from Tranilast-treated mice shows decreased levels of TGF beta1, endoglin, and significantly higher levels of p53 and cleaved PARP. Cleaved caspase 3 expression is significantly elevated in Tranilast-treated mouse breast tumors. To conclude, Tranilast induces cellular and molecular changes in murine breast cancer that can be exploited in preclinical therapeutic trials.
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Tranilast inhibits the growth and metastasis of mammary carcinoma
Anti-Cancer Drugs, 2009Co-Authors: Rabindranath Chakrabarti, Venkateswaran Subramaniam, Serge Jothy, Salma Abdalla, Gerald J PrudhommeAbstract:Tranilast (N-[3,4-dimethoxycinnamonyl]-anthranilic acid) is a drug of low toxicity that is orally administered, and has been used clinically in Japan as an antiallergic and antifibrotic agent. Its antifibrotic effect is thought to depend on the inhibition of transforming growth factor-beta (TGF-beta). It has also been shown to exert antitumor effects, but its mode of action is unclear. Here, we explored the antitumor effects of Tranilast in vitro and in vivo. Tranilast inhibited the proliferation of several tumor cell lines including mouse mammary carcinoma (4T1), rat mammary carcinoma stem cell (LA7), and human breast carcinoma (MDA-MB-231 and MCF-7). Tranilast blocked cell-cycle progression in vitro. In the highly metastatic 4T1 cell line, Tranilast inhibited phospho-Smad2 generation, consistent with a blockade of TGF-beta signaling. It also inhibited the activation of MAP kinases (extracellularly regulated kinase 1 and 2 and JNK), which have been linked to TGF-beta-dependent epithelial-to-mesenchymal transition and, indeed, it blocked epithelial-to-mesenchymal transition. Although Tranilast only partially inhibited TGF-beta production by 4T1 tumor cells, it potently inhibited the production of TGF-beta, interferon-gamma, IL-6, IL-10, and IL-17 by lymphoid cells, suggesting a general anti-inflammatory activity. In vivo, female BALB/c mice were inoculated with syngeneic 4T1 cells in mammary fat pads and treated with Tranilast by gavage. Tranilast reduced (>50%) the growth of the primary tumor. However, its effects on metastasis were more striking, with more than 90% reduction of metastases in the lungs and no metastasis in the liver. Thus, Tranilast has potential activity as an antimetastatic agent in breast cancer.
J Dichgans - One of the best experts on this subject based on the ideXlab platform.
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n 3 4 dimethoxycinnamoyl anthranilic acid Tranilast inhibits transforming growth factor β release and reduces migration and invasiveness of human malignant glioma cells
International Journal of Cancer, 2001Co-Authors: Michael Platten, Christine Wildbode, Wolfgang Wick, Jens Leitlein, J Dichgans, Michael WellerAbstract:Extensive infiltration of normal brain tissue and suppression of anti-tumor immune surveillance mediated by molecules such as transforming growth factor-β (TGF-β) are key biological features that contribute to the malignant phenotype of human gliomas. Tranilast (N-[3,4-dimethoxycinnamoyl]-anthranilic acid) is an anti-allergic compound used clinically to control atopic and fibrotic disorders. These effects are attributed to the suppression of TGF-β1 synthesis and interference with growth factor–mediated proliferation and migration of fibroblasts and vascular smooth muscle cells. Here, we show that Tranilast inhibits DNA synthesis and proliferation of human malignant glioma cells and promotes p21 accumulation in the absence of cytotoxicity. Further, Tranilast reduces the release of TGF-β1 and TGF-β2 by glioma cells and inhibits migration, chemotactic responses and invasiveness. These effects are not associated with a reduction of αvβ3 integrin expression at the cell surface but appear to involve inhibition of matrix metalloproteinase-2 expression and activity. Neither the Tranilast-mediated inhibition of proliferation nor the inhibition of migration was counteracted by supplementation with exogenous TGF-β. Finally, Tranilast administered orally inhibited the growth of experimental 9L rat gliomas and reduced expression of TGF-β2in vivo. We conclude that Tranilast might be a useful therapeutic agent for the treatment of human malignant glioma because of a TGF-β-independent abrogation of the malignant phenotype of proliferation, migration and invasiveness and because of the antagonism of TGF-β-associated immunosuppression. © 2001 Wiley-Liss, Inc.
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n 3 4 dimethoxycinnamoyl anthranilic acid Tranilast inhibits transforming growth factor beta relesase and reduces migration and invasiveness of human malignant glioma cells
International Journal of Cancer, 2001Co-Authors: Michael Platten, Christine Wildbode, Wolfgang Wick, Jens Leitlein, J Dichgans, Michael WellerAbstract:Extensive infiltration of normal brain tissue and suppression of anti-tumor immune surveillance mediated by molecules such as transforming growth factor-beta (TGF-beta) are key biological features that contribute to the malignant phenotype of human gliomas. Tranilast (N-[3,4-dimethoxycinnamoyl]-anthranilic acid) is an anti-allergic compound used clinically to control atopic and fibrotic disorders. These effects are attributed to the suppression of TGF-beta1 synthesis and interference with growth factor-mediated proliferation and migration of fibroblasts and vascular smooth muscle cells. Here, we show that Tranilast inhibits DNA synthesis and proliferation of human malignant glioma cells and promotes p21 accumulation in the absence of cytotoxicity. Further, Tranilast reduces the release of TGF-beta1 and TGF-beta2 by glioma cells and inhibits migration, chemotactic responses and invasiveness. These effects are not associated with a reduction of alpha(v)beta(3) integrin expression at the cell surface but appear to involve inhibition of matrix metalloproteinase-2 expression and activity. Neither the Tranilast-mediated inhibition of proliferation nor the inhibition of migration was counteracted by supplementation with exogenous TGF-beta. Finally, Tranilast administered orally inhibited the growth of experimental 9L rat gliomas and reduced expression of TGF-beta2 in vivo. We conclude that Tranilast might be a useful therapeutic agent for the treatment of human malignant glioma because of a TGF-beta-independent abrogation of the malignant phenotype of proliferation, migration and invasiveness and because of the antagonism of TGF-beta-associated immunosuppression.
