The MYCN 5′ UTR as a therapeutic target in neuroblastoma

Volegova, Marina P.; Brown, Lauren E.; Banerjee, Ushashi; Dries, Ruben; Sharma, Bandana; Kennedy, Alyssa; Porco, John A.; George, Rani E.

doi:10.1016/j.celrep.2024.114134

Cited by 1 publication

(1 citation statement)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Future studies will also aim to define the set of mRNAs that are regulated by (−)-20 and related compounds via DDX3 in GBM stem cells using ribosome profiling, RNA Bindn-Seq, 41 and RNA-seq, 66,67 techniques which have been reported using rocaglates, and potentially PAR-CLIP, which has been used to identify binding between DDX3 and helix 16 on the human 40S ribosome 68 and to isolate RNA transcripts that copurify with endogenous eIF4A1 in MYCN-amplified neuroblastoma cells in the presence of an amidino rocaglate (ADR) derivative. 69 ■ METHODS Cell Culture. Glioblastoma stem cell lines GBM0308, BT145, and BT112 were cultured in neurobasal medium (NBE) (ThermoFisher Scientific) containing N-2 and B-27 supplements (ThermoFisher Scientific), EGF (Stem Cell Technologies), bFGF (Stem Cell Technologies), L-glutamine (ThermoFisher Scientific), and penicillin−streptomycin (Sigma-Aldrich) as described previously.…”

Section: ■ Conclusionmentioning

confidence: 99%

Identification of Rocaglate Acyl Sulfamides as Selective Inhibitors of Glioblastoma Stem Cells

Wang,

Thakare,

Chitale

et al. 2024

ACS Cent. Sci.

View full text Add to dashboard Cite

Glioblastoma (GBM) is the most aggressive and frequently occurring type of malignant brain tumor in adults. The initiation, progression, and recurrence of malignant tumors are known to be driven by a small subpopulation of cells known as tumor-initiating cells or cancer stem cells (CSCs). GBM CSCs play a pivotal role in orchestrating drug resistance and tumor relapse. As a prospective avenue for GBM intervention, the targeted suppression of GBM CSCs holds considerable promise. In this study, we found that rocaglates, compounds which are known to inhibit translation via targeting of the DEAD-box helicase eIF4A, exert a robust, dose-dependent cytotoxic impact on GBM CSCs with minimal killing of nonstem GBM cells. Subsequent optimization identified novel rocaglate derivatives (rocaglate acyl sulfamides or Roc ASFs) that selectively inhibit GBM CSCs with nanomolar EC50 values. Furthermore, comparative evaluation of a lead CSC-optimized Roc ASF across diverse mechanistic and target profiling assays revealed suppressed translation inhibition relative to that of other CSC-selective rocaglates, with enhanced targeting of the DEAD-box helicase DDX3X, a recently identified secondary target of rocaglates. Overall, these findings suggest a promising therapeutic strategy for targeting GBM CSCs.

show abstract