Inhibition of Angiogenesis Induces Chromaffin Differentiation and Apoptosis in Neuroblastoma

Wassberg, Erik; Hedborg, Fredrik; Sköldenberg, Erik; Stridsberg, Mats; Christofferson, Rolf

doi:10.1016/s0002-9440(10)65286-8

Cited by 51 publications

(45 citation statements)

References 32 publications

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“…Three angiostatic agents have been tested recently: the synthetic analogue of fumagillin TNP-470, 39,40 the endogenous steroid 2-methoxyestradiol and its derivative 2-propylestradiol. 41,42 In the TNP-470-treated animals, not only was a significant reduced tumor growth rate observed, but also a reduced microvascular density and a reduction of the fraction of viable tumor cells. 39,40 Furthermore, Wassberg et al 42 demonstrated that the angiogenesis inhibitor TNP-470 induces chromaffin differentiation and apoptosis in NB.…”

Section: Discussionmentioning

confidence: 99%

“…41,42 In the TNP-470-treated animals, not only was a significant reduced tumor growth rate observed, but also a reduced microvascular density and a reduction of the fraction of viable tumor cells. 39,40 Furthermore, Wassberg et al 42 demonstrated that the angiogenesis inhibitor TNP-470 induces chromaffin differentiation and apoptosis in NB. These findings are in agreement with previous observations that apoptotic areas can be considered good prognostic markers in NB.…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of neuroblastoma-induced angiogenesis by fenretinide

et al. 2001

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Retinoids are a class of natural or synthetic compounds that participate in the control of cell proliferation, differentiation and fetal development. The synthetic retinoid fenretinide (HPR) inhibits carcinogenesis in various animal models. Retinoids have also been suggested to be effective inhibitors of angiogenesis. The effects of HPR on certain endothelial cell functions were investigated in vitro, and its effects on angiogenesis was studied in vivo, by using the chorioallantoic membrane (CAM) assay. HPR inhibited vascular endothelial growth factor-(VEGF-) and fibroblast growth factor-2-(FGF-2)-induced endothelial cell proliferation without affecting endothelial motility; moreover, HPR inhibited growth factor-induced angiogenesis in the CAM assay. Furthermore, a significant antiangiogenic potential of HPR has also been observed in neuroblastoma (NB) biopsy-induced angiogenesis in vivo. We previously demonstrated that supernatants derived from NB cell lines stimulated endothelial cell proliferation. In the present study, we found that this effect was abolished when NB cells were incubated in the presence of HPR. VEGF-and FGF-2-specific ELISA assays, performed on both NB cells derived from conditioned medium and cellular extracts, indicated no consistent effect of HPR on the level of these angiogenic cytokines. Moreover, RT-PCR analysis of VEGF and FGF-2 gene expression confirmed the above lack of effect. HPR was also able to significantly repress the spontaneous growth of endothelial cells, requiring at least 48 -72 hr of treatment with HPR, followed by a progressive accumulation of cells in G 1 at subsequent time points. Finally, immunohistochemistry experiments performed in the CAM assay demonstrated that endothelial staining of both VEGF receptor 2 and FGF-2 receptor-2 was reduced after implantation of HPR-loaded sponges, as compared to control CAMs. These data suggest that HPR exerts its antiangiogenic activity through both a direct effect on endothelial cell proliferative activity and an inhibitory effect on the responsivity of the endothelial cells to the proliferative stimuli mediated by angiogenic growth factors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inhibition of neuroblastoma-induced angiogenesis by fenretinide

et al. 2001

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“…The enhanced antitumour effect of chemotherapeutic agents when combined with AAT (Teicher et al, 1992(Teicher et al, , 1994Sweeney et al, 2001) is probably not only due to differences in vascularisation, perfusion and drug delivery, but also an increase in tumour cell apoptosis (Kamiya et al, 1999;Wassberg et al, 1999). VEGF is a recognised chemoprotectant, particularly for drugs that inhibit microtubules, by reducing the proapoptotic effect of chemotherapy (Tran et al, 2002).…”

Section: Tumour Growth Delaymentioning

confidence: 99%

Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11

Wildiers¹,

Guetens²,

Boeck³

et al. 2003

Br J Cancer

304

150

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Promising preclinical activity with agents blocking the function of vascular endothelial growth factor (VEGF) has been observed in various cancer types, especially with combination therapy. However, these drugs decrease microvessel density, and it is not known whether this reduced vessel density (VD) results in decreased delivery of concomitantly administered classical anticancer drugs. We designed an in vivo study to investigate the relation between VEGF-blocking therapy, tumoral blood vessels, and intratumoral uptake of anticancer drugs. Nude NMRI mice bearing colon adenocarcinoma (HT29) were treated with the anti-VEGFmAb A4.6.1 or placebo. After 1 week, CPT-11 was administered 1 h prior to killing the animals. In A4.6.1 treated tumours, there was a significant decrease in VD, more pronounced with potentially functional large vessels than endothelial cords. Interestingly, a trend to increased intratumoral CPT-11 concentration was observed (P ¼ 0.09). In parallel, we measured an increase in tumour perfusion, as estimated by high-performance liquid chromatography determination of intratumoural Hoechst 33342 concentration. In the growth delay study, CPT-11 was at least equally effective with or without pretreatment with A4.6.1. These data suggest that tumour vascular function and tumour uptake of anticancer drugs improve with VEGF-blocking therapy, and indicate the relevance for further investigations.

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“…The incidence is 10.5 per million children under 15 years of age per year, with little variation between Europe and North America, and there are 700 new cases diagnosed in the United States each year (Stiller and Parkin 1992;Brodeur 2003). NBs grow rapidly; often giving rise to metastasis (Wassberg et al 1999). Therapy resistance to anticancer drugs represents the major limitation to the effectiveness of clinical treatment.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity and genotoxicity of zingiberene on different neuron cell lines in vitro

et al. 2014

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The main objective of this study is to investigate the cytotoxic, genotoxic and antioxidant properties of zingiberene (ZBN) in an in vitro rat brain cell culture study. The cytotoxic effect was determined against the rat neuron and N2a neuroblastoma (N2a-NB) cell lines using the 3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, while the antioxidant activity was assessed using the total antioxidant capacity (TAC) and total oxidative stress (TOS) assays. The effects on DNA damage were also evaluated in this study by the single cell gel electrophoresis assay. The results indicated that ZBN has an anti-proliferative activity suppressing the proliferation of N2a-NB cells at concentrations over 50 mg L -1 and neuron cells at concentrations over 150 mg L -1. In addition, ZBN treatments at higher doses (B50 mg L -1 ) led to increases of TOS levels in N2a-NB cell cultures. However 25 mg L -1 of ZBN treatment caused increases of TAC levels in cultured neuron and N2a-NB cell cultures while ZBN at doses of 10-400 mg L -1 did not increase the number of total damage score in both cell lines. This study clearly indicates that ZBN has a significant potential to be used as a natural anticancer agent in cultured N2a-NBs.

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Inhibition of Angiogenesis Induces Chromaffin Differentiation and Apoptosis in Neuroblastoma

Abstract: Angiogenesis is a prerequisite for the growth and metastasis of tumors.

Cited by 51 publications

References 32 publications

Inhibition of neuroblastoma-induced angiogenesis by fenretinide

Inhibition of neuroblastoma-induced angiogenesis by fenretinide

Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11

Cytotoxicity and genotoxicity of zingiberene on different neuron cell lines in vitro

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