Time course of H2A.X phosphorylation after SAHA and Actinomycin D treatment. LA1-55n cells were treated (+) or not (-) with 0.1 nM of actinomycin D (ActD) in the presence (+) or in the absence (-) of 1 μ M SAHA. Indicated protein expression was determined by Western blot analysis at the indicated times after the treatment. (DOCX 710 kb

Albert Tauler (111391)

Constanza Cortes (3766423)

Eugènia Almacellas (3766420)

George Thomas (80785)

Javier Hernández-Losa (105308)

Joan Ferreres (3766426)

Santiago Ambrosio (111388)

Sara Kozma (3766432)

Sonia Veiga (3766429)

Molecular Cancer

English

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Additional file 2: Figure S2. of Effect of low doses of actinomycin D on neuroblastoma cell lines

Lutz, Andrea

Scholarworks@GVSU

Fishladder: A Student Journal of Art and WritingVolume 2Issue 1 Spring 2004 Article 1310-18-2011UntitledAndrea LutzFollow this and additional works at: http://scholarworks.gvsu.edu/fishladderThis Article is brought to you for free and open access by ScholarWorks@GVSU. It has been accepted for inclusion in Fishladder: A Student Journal ofArt and Writing by an authorized administrator of ScholarWorks@GVSU. For more information, please contact scholarworks@gvsu.edu.Recommended CitationLutz, Andrea (2004) "Untitled," Fishladder: A Student Journal of Art and Writing: Vol. 2: Iss. 1, Article 13.Available at: http://scholarworks.gvsu.edu/fishladder/vol2/iss1/13

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Background: Neuroblastoma is a malignant embryonal tumor occurring in young children, consisting of undifferentiated neuroectodermal cells derived from the neural crest. Current therapies for high-risk neuroblastoma are insufficient, resulting in high mortality rates and high incidence of relapse. With the intent to find new therapies for neuroblastomas, we investigated the efficacy of low-doses of actinomycin D, which at low concentrations preferentially inhibit RNA polymerase I-dependent rRNA trasncription and therefore, ribosome biogenesis. Methods: Neuroblastoma cell lines with different p53 genetic background were employed to determine the response on cell viability and apoptosis of low-dose of actinomycin D. Subcutaneously-implanted SK-N-JD derived neuroblastoma tumors were used to assess the effect of low-doses of actinomycin D on tumor formation. Results: Low-dose actinomycin D treatment causes a reduction of cell viability in neuroblastoma cell lines and that this effect is stronger in cells that are wild-type for p53. MYCN overexpression contributes to enhance this effect, confirming the importance of this oncogene in ribosome biogenesis. In the wild-type SK-N-JD cell line, apoptosis was the major mechanism responsible for the reduction in viability and we demonstrate that treatment with the MDM2 inhibitor Nutlin-3, had a similar effect to that of actinomycin D. Apoptosis was also detected in p53(-/-)deficient LA1-55n cells treated with actinomycin D, however, only a small recovery of cell viability was found when apoptosis was inhibited by a pan-caspase inhibitor, suggesting that the treatment could activate an apoptosis-independent cell death pathway in these cells. We also determined whether actinomycin D could increase the efficacy of the histone deacetylase inhibitor, SAHA, which is in being used in neuroblastoma clinical trials. We show that actinomycin D synergizes with SAHA in neuroblastoma cell lines. Moreover, on subcutaneously-implanted neuroblastoma tumors derived from SK-N-JD cells, actinomycin D led to tumor regression, an effect enhanced in combination with SAHA. Conclusions: The results presented in this work demonstrate that actinomycin D, at low concentrations, inhibits proliferation and induces cell death in vitro, as well as tumor regression in vivo. From this study, we propose that use of ribosome biogenesis inhibitors should be clinically considered as a potential therapy to treat neuroblastomas

Cortés, Constanza

Pereira Da Veiga, Sónia Rosa

Almacellas i Canals, Eugènia

Hernández-Losa, Javier

Ferreres, Joan C.

Kozma, Sara C.

Ambrosio Viale, Santiago

Thomas, George

Tauler Girona, Albert

Diposit Digital de la Universitat de Barcelona

Effect of low doses of actinomycin D on neuroblastoma cell lines

https://figshare.com/articles/Additional_file_2_Figure_S2_of_Effect_of_low_doses_of_actinomycin_D_on_neuroblastoma_cell_lines/4674424

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Diposit Digital de la Universitat de Barcelona