{"doi":"10.18632/oncotarget.27697","title":"Preclinical evaluation of the anti-tumor activity of pralatrexate in high-risk neuroblastoma cells","abstract":"// Rachael A. Clark 1 , * , Sora Lee 1 , * , Jingbo Qiao 1 and Dai H. Chung 1 1 Department of Surgery, Division of Pediatric Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA * These authors contributed equally to this work Correspondence to: Dai H. Chung, email: dai.chung@utsouthwestern.edu Keywords: neuroblastoma; pralatrexate; N-myc; folate metabolism Received: February 14, 2020     Accepted: July 07, 2020     Published: August 11, 2020 ABSTRACT Introduction: Pralatrexate is a folate analogue inhibitor of dihydrofolate reductase exhibiting high affinity for reduced folate carrier-1 with antineoplastic and immunosuppressive activities, similar to methotrexate. Despite advances in multi-modality treatment strategies, the survival rates for children with high-risk neuroblastoma have failed to improve. Therefore, the intense research continues in order to identify the ideal novel agent or combination of chemotherapy drugs to treat high-risk neuroblastoma. Materials and Methods: Four human neuroblastoma cell lines were used to determine IC 50 values of select chemotherapy agents. Antiproliferative effects of pralatrexate were assessed by adherent and non-adherent colony formation assays. Cell cycle arrest and apoptosis were measured by flow cytometry and immunoblotting. PDX tissue culture was used to assess ex vivo efficacy. Results: Treatment with pralatrexate in all four neuroblastoma cell lines blocked cell growth in 2D and 3D culture conditions in a time-dependent manner. The potency of pralatrexate was ten-fold stronger than methotrexate, as measured by IC 50 . Pralatrexate-induced apoptosis was confirmed by caspase-3 activation and PARP cleavage. MYCN and SLC19A1 mRNA expressions were decreased with pralatrexate in MYCN -amplified neuroblastoma cells. Conclusions: Pralatrexate demonstrated effective inhibition of cell growth and viability. The higher potency of pralatrexate compared to methotrexate, a drug with high levels of toxicity, suggests pralatrexate may be a safer alternative to methotrexate as an effective chemotherapeutic agent in the treatment of patients with high-risk neuroblastoma.","journal":"Oncotarget","year":2020,"id":109029,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9572,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":521065,"name":"Sora Lee","orcid":"0000-0002-0075-7324","position":1,"is_corresponding":false},{"id":425030,"name":"Jingbo Qiao","orcid":null,"position":2,"is_corresponding":false},{"id":289614,"name":"Dai H. Chung","orcid":"0000-0001-7044-940X","position":3,"is_corresponding":false},{"id":258691,"name":"Rachael A. Clark","orcid":"0000-0002-6105-5764","position":0,"is_corresponding":true}],"reference_count":13,"raw_metadata":null,"created_at":"2026-07-18T23:12:46.854423Z","pmid":"32850011","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}