Thalidomide and Prednisolone Inhibit Growth Factor-Induced Human Retinal Pigment Epithelium Cell Proliferation in vitro

Kaven, Corinna; Spraul, Christoph W.; Zavazava, Nicholas; Lang, Gerhard K.; Lang, Gabriele E.

doi:10.1159/000050875

Cited by 22 publications

(16 citation statements)

References 28 publications

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“…41 So far, thalidomide is reported to down-regulate VEGF expression in lung carcinoma cells at 0.6 g/mL to 6 g/mL 9 and to inhibit retinal epithelial cell proliferation at 50 g/mL. 42 The effective concentrations of thalidomide in zebrafish embryos seem to be higher as compared with the previous in vitro experiments, suggesting the loss of activity by spontaneous metabolism in the water and the requirement of its conversion to active metabolites in zebrafish as well as in the mouse model. 43 Synthetic ceramide with a short carbon chain such as C2-ceramide has been employed because of its cell permeability and functional mimicry to physiologic ceramide.…”

Section: Discussionmentioning

confidence: 99%

Thalidomide-induced antiangiogenic action is mediated by ceramide through depletion of VEGF receptors, and is antagonized by sphingosine-1-phosphate

Yabu

Tomimoto

Taguchi

et al. 2005

Blood

123

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Section: Discussionmentioning

confidence: 99%

Thalidomide-induced antiangiogenic action is mediated by ceramide through depletion of VEGF receptors, and is antagonized by sphingosine-1-phosphate

Yabu

Tomimoto

Taguchi

et al. 2005

Blood

123

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“…In two studies, Kaven et al and Spraul et al indicated that thalidomide dissolved in DMSO showed an inhibitory effect on the migration and proliferation of rabbit pigment epithelium (RPE) cells compared to controls without any supplement (7,8). However, these authors did not use DMSO alone as a control.…”

Section: Discussionmentioning

confidence: 99%

DMSO exhibits similar cytotoxicity effects to thalidomide in mouse breast cancer cells

Aydemir

Fışkın

2012

Oncol Lett

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Abstract. The purpose of this study was to evaluate the cytotoxic effect of thalidomide on 4T1 and 4THMpc mouse breast cancer cell lines. Mouse breast cancer cells (4T1) and cells derived from metastatic lesions (4THMpc) were treated with various doses of thalidomide [10 -2 -100 µM dissolved in dimethyl sulfoxide (DMSO) as recommended] and 1.4 µM DMSO (maximum DMSO concentration in the highest thalidomide dose) as a DMSO control against the untreated control groups. MTT was used to evaluate the cytotoxic effects of the treatments. Therefore, we investigated the role of thalidomide on apoptosis. A fluorometric EnzChek caspase-3 enzyme activity assay kit was used to evaluate the apoptotic effects of thalidomide. Thalidomide dissolved in DMSO exhibited cytotoxic effects on 4T1 and 4THMpc cells compared to the control groups incubated without any supplement. Treatment with thalidomide resulted in apoptosis of mouse breast cancer cells in a time-and dose-dependent manner as demonstrated by caspase-3 enzyme activity. However, DMSO alone suppressed cell proliferation more effectively than thalidomide. In cultured mouse breast cancer cells the inhibitory effect of thalidomide may be partially attributed to the solvent DMSO alone. IntroductionBreast cancer, which is the second leading cause of cancer mortality in women, occurs at a high frequency (1). Although there have been significant advances in diagnosing and treating breast cancer, a number of major unresolved clinical and scientific problems remain and investigations are ongoing (2).Thalidomide [a(N-phthalimido)-glutarimide, a derivative of glutamic acid with two rings and two optically active forms] is an odorless, white crystalline compound with low solubility in water and has a cytotoxic effect on a number of cancer cell lines, including breast cancer (3,4).Thalidomide has been shown to be clinically useful in a number of situations due to its ability to inhibit TNF-α synthesis. However, its use is restricted by potentially serious side effects, including teratogenicity (5). Furthermore, insolubility may cause serious problems in terms of systemic bioavailability. The major solvent of thalidomide is dimethyl sulfoxide (DMSO) and it has been shown to mimic the cytotoxic effects of thalidomide (6).The aim of this study was to evaluate the effect of thalidomide and DMSO on the viability of cultured 4T1 and 4THMpc mouse breast cancer cell lines. Materials and methodsThalidomide. Thalidomide was purchased from SigmaAldrich (Cat. No. T 144; St. Louis, MO, USA). A 100 µM stock solution dissolved in DMSO (14.08 mM) was prepared and then the solution was aliquoted into standard Eppendorf tubes in quantities of 500 µl for daily assays. These aliquots were stored at -70˚C until required.Cell lines and in vitro cell culture conditions. 4T1 breast cancer cells and 4T1 heart metastases post capsaicin (4THM), a cell line obtained from orthotopically transplanted 4T1 breast cancer cells, were used in this study. The cell lines were a kind gift from Dr Nuray Erin (Akdeniz Unive...

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“…[1][2][3][4][5][6][7][8][9] It might be species specific 8 and caused by the action of one of its metabolites. 8 The same may be true for DMSO.…”

Section: Discussionmentioning

confidence: 99%

DMSO mimics inhibitory effect of thalidomide on choriocapillary endothelial cell proliferation in culture

Eter

Spitznas

2002

British Journal of Ophthalmology

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Aim: To evaluate the effect of thalidomide on bovine choriocapillary endothelial cell proliferation. Methods: Posterior segments of bovine eyes were incubated with trypsin. After digestion of the tapetum, pieces of Bruch's membrane with the adherent choriocapillaris were scraped, digested again with a cocktail of enzymes, washed and cultured in MCDB 131 medium. Cells were incubated with 100 µg/ml thalidomide (dissolved in DMSO as recommended). Control cultures were incubated with DMSO alone or without any supplement. Cell proliferation after 24 hours was determined in a counting chamber. Purity of the cultures was controlled by immunohistochemical staining and labelling with low density lipoprotein. Results: Thalidomide dissolved in DMSO inhibited proliferation of choriocapillary endothelial cells compared to control cultures incubated without any supplement. However, DMSO alone suppressed cell proliferation equally well. Conclusion: In cultured bovine choriocapillary cells the inhibiting effect of thalidomide may at least in part be attributed to the solvent DMSO alone. C horoidal neovascularisation (CNV) in age related macular degeneration is the leading cause of legal blindness in people aged 65 years and older. Laser treatment, photodynamic therapy, surgical interventions, and pharmacological approaches have been undertaken to find an adequate therapy. Since CNV represents neovascular growth from the choriocapillaris, anti-angiogenic drugs should be found that inhibit choriocapillary endothelial cell growth.Thalidomide (α[N-phthalimido]-glutarimide) may have an inhibiting effect on new blood vessel growth. It is an odourless, white crystalline compound with low solubility in water. It is a derivative of glutamic acid with two rings and two optically active forms. 1 It has been suggested that thalidomide exerts its antiangiogenic properties by generating toxic hydroxyl radicals. 2In vivo it has been shown to have an anti-angiogenic effect against neovascular growth induced by vascular endothelial growth factor (VEGF) in the rabbit cornea, 3 as well as against neovascularisation induced by basic fibroblast growth factor (bFGF) or VEGF in the mouse cornea. 4 In vitro thalidomide has been shown to be effective in inhibiting human umbilical vein endothelial cell proliferation, 5 as well as retinal pigment epithelial cell proliferation and migration. 6 The aim of this study was to evaluate the effect of thalidomide on the proliferation of cultured bovine choriocapillary endothelial (CCE) cells. MATERIALS AND METHODSIsolation and culture of choroidal endothelial cells Isolation and cultivation of choriocapillary endothelial cells was performed as described earlier (submitted for publication). In brief, bovine eyes were bisected and the anterior segment, vitreous, and retina were removed. The remaining eyecup was filled with Dulbecco's modified Eagle's medium (DMEM) containing 3% amphotericin B, 600 IU/ml penicillin, + 600 µg/ml streptomycin and was washed twice. Retinal pigment epithelium (RPE) cells were removed f...

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Thalidomide and Prednisolone Inhibit Growth Factor-Induced Human Retinal Pigment Epithelium Cell Proliferation in vitro

Cited by 22 publications

References 28 publications

Thalidomide-induced antiangiogenic action is mediated by ceramide through depletion of VEGF receptors, and is antagonized by sphingosine-1-phosphate

Thalidomide-induced antiangiogenic action is mediated by ceramide through depletion of VEGF receptors, and is antagonized by sphingosine-1-phosphate

DMSO exhibits similar cytotoxicity effects to thalidomide in mouse breast cancer cells

DMSO mimics inhibitory effect of thalidomide on choriocapillary endothelial cell proliferation in culture

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