American Association for Cancer Research
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15357163mct141103-sup-143199_1_supp_2922900_nm4rx5.pdf (452.46 kB)

Supplementary Figures 1 through 11 and Supplementary Figure Legends from Preclinical Evaluation of a Novel RXR Agonist for the Treatment of Neuroblastoma

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posted on 2023-04-03, 14:20 authored by Alicia M. Waters, Jerry E. Stewart, Venkatram R. Atigadda, Elizabeth Mroczek-Musulman, Donald D. Muccio, Clinton J. Grubbs, Elizabeth A. Beierle

Figure S1 / S2. UAB30 activated caspase 3. Figure S3. UAB30 increased nestin protein. Figure S4 / S5. UAB30 decreased neuroblastoma cellular proliferation. Figure S6 / S7. UAB30 did not alter expression or phosphorylation of ERK1/2 or AKT. Figure S8 / S9. UAB30 did not alter p53 expression. Figure S10. UAB30 did not affect MYCN expression. Figure S11. Tumor weight to animal weight ratio.

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ARTICLE ABSTRACT

Neuroblastoma remains a common cause of pediatric cancer deaths, especially for children who present with advanced stage or recurrent disease. Currently, retinoic acid therapy is used as maintenance treatment to induce differentiation and reduce tumor recurrence following induction therapy for neuroblastoma, but unavoidable side effects are seen. A novel retinoid, UAB30, has been shown to generate negligible toxicities. In the current study, we hypothesized that UAB30 would have a significant impact on multiple neuroblastoma cell lines in vitro and in vivo. Cellular survival, cell-cycle analysis, migration, and invasion were studied using AlamarBlue assays, FACS, and Transwell assays, respectively, in multiple cell lines following treatment with UAB30. In addition, an in vivo murine model of human neuroblastoma was utilized to study the effects of UAB30 upon tumor xenograft growth and animal survival. We successfully demonstrated decreased cellular survival, invasion, and migration, cell-cycle arrest, and increased apoptosis after treatment with UAB30. Furthermore, inhibition of tumor growth and increased survival was observed in a murine neuroblastoma xenograft model. The results of these in vitro and in vivo studies suggest a potential therapeutic role for the low toxicity synthetic retinoid X receptor selective agonist, UAB30, in neuroblastoma treatment. Mol Cancer Ther; 14(7); 1559–69. ©2015 AACR.