Effect of thalidomide, octreotide, and prednisolone on the migration and proliferation of RPE cells in vitro

Spraul, Christoph W.; Kaven, Corinna; Kampmeier, Jürgen; Lang, Gerhard K.; Lang, Gabriele E.

doi:10.1076/ceyr.19.6.483.5281

Cited by 20 publications

(14 citation statements)

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“…The influence of corticosteroids on RPE cells has been reported by several authors, presenting a biphasic effect of dexamethasone [32, 33]and prednisolone [19]. In this study, prednisolone was an effective inhibitor of human RPE cell proliferation at a dose of 100 ng/ml and kept its inhibitory potency even after growth factor stimulation of the cells.…”

Section: Discussionsupporting

confidence: 59%

“…Yet, the mechanism how thalidomide modulates neovascularization and angiogenesis is still an unsolved problem. The effect of thalidomide on the RPE was studied for the first time by Spraul et al [19]. They presented a significant inhibition of bovine RPE cell migration and proliferation by thalidomide at doses of <10 µg/ml.…”

Section: Discussionmentioning

confidence: 99%

“…The cells were growth arrested by pretreating in a minimum-medium (HAM’s F-10 + 1% bovine serum albumin, BSA) after which distinct assays were performed: (i) HAM’s F-10 + 1% BSA plus addition of each of the growth factors at a concentration of 10 ng/ml (the concentration of 10 ng/ml was previously confirmed to stimulate RPE cell proliferation) for 24 h; (ii) HAM’s F-10 +1 % BSA plus either thalidomide (50 µg/ml) or prednisolone (100 ng/ml) for 24 h (the drug doses have been confirmed to inhibit RPE cell proliferation in prior experiments [19], and furthermore, cytotoxicity was excluded by the trypan blue-test); (iii) HAM’s F-10 + 1% BSA plus growth factor (each 10 ng/ml) for 24 h, plus thalidomide (50 µg/ml) or prednisolone (100 ng/ml) for 24 h; (iv) HAM’s F-10 + 10% FCS as a control for cellular vitality, and (v) HAM’s F-10 + 1% BSA as a negative control for basal cell proliferation. Cells were incubated at 37°C in a humidified CO 2 atmosphere.…”

Section: Methodsmentioning

confidence: 99%

“…Thalidomide and corticosteroids are therapeutic agents that are considered to have beneficial effects on choroidal neovascularization [14, 15, 16, 17, 18]. Investigations of our group revealed that thalidomide and prednisolone are effective inhibitors of RPE cell migration and proliferation at certain concentrations [19]. Still, these effects may not remain in cells that have previously been stimulated by growth factors as takes place during the development of AMD.…”

Section: Introductionmentioning

confidence: 99%

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

Kaven

Spraul²,

Zavazava³

et al. 2001

Ophthalmologica

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Thalidomide and prednisolone were recently introduced as treatment modalities in age-related macular degeneration (AMD). Growth factor-induced activation of retinal pigment epithelial (RPE) cells is a crucial event in this disease. The purpose was to examine the effect of thalidomide and prednisolone on growth factor-preactivated RPE cells. Human RPE cells were stimulated with 10 ng/ml platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), or vascular endothelial growth factor (VEGF) for 24 h. Afterwards, thalidomide (50 µg/ml) or prednisolone (100 ng/ml) were added for 24 h. RPE cell proliferation was determined by [³H]-thymidine incorporation. PDGF and bFGF significantly stimulated human RPE cell proliferation (p < 0.005), the value for VEGF stimulation was not significant (p = 0.3). The effect of the growth factors was diminished after addition of thalidomide and prednisolone (p < 0.005). The current study shows that the inhibitory properties of thalidomide and prednisolone remain even after growth factor activation of the cells.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Kaven

Spraul²,

Zavazava³

et al. 2001

Ophthalmologica

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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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Automated in Vitro Screening of Teratogens

Walmod

Berezin

Gallagher

et al. 2002

Toxicology and Applied Pharmacology

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Effect of thalidomide, octreotide, and prednisolone on the migration and proliferation of RPE cells in vitro

Abstract: Although the main effect of thalidomide, octreotide, and prednisolone when treating patients with choroidal neovascular membranes is probably related to the inhibition of angiogenesis it should be kept in mind that these substances may additionally inhibit RPE proliferation and migration.

Cited by 20 publications

References 16 publications

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

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

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

Automated in Vitro Screening of Teratogens

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