{"doi":"10.3390/cancers13246176","title":"Altertoxin II, a Highly Effective and Specific Compound against Ewing Sarcoma","abstract":"A screening program designed to identify natural products with selective cytotoxic effects against cell lines representing different types of pediatric solid tumors led to the identification of altertoxin II as a highly potent and selective cytotoxin against Ewing sarcoma cell lines. Altertoxin II, but not the related compounds altertoxin I and alteichin, was highly effective against every Ewing sarcoma cell line tested, with an average 25-fold selectivity for these cells as compared to cells representing other pediatric and adult cancers. Mechanism of action studies revealed that altertoxin II causes DNA double-strand breaks, a rapid DNA damage response, and cell cycle accumulation in the S phase. Our studies also demonstrate that the potent effects of altertoxin II are partially dependent on the progression through the cell cycle, because the G1 arrest initiated by a CDK4/6 inhibitor decreased antiproliferative potency more than 10 times. Importantly, the cell-type-selective DNA-damaging effects of altertoxin II in Ewing sarcoma cells occur independently of its ability to bind directly to DNA. Ultimately, we found that altertoxin II has a dose-dependent in vivo antitumor efficacy against a Ewing sarcoma xenograft, suggesting that it has potential as a therapeutic drug lead and will be useful to identify novel targets for Ewing-sarcoma-specific therapies.","journal":"Cancers","year":2021,"id":203126,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":336868,"name":"Wentao Dai","orcid":"0000-0002-0762-919X","position":1,"is_corresponding":false},{"id":783816,"name":"Saikat Haldar","orcid":"0000-0002-5968-5230","position":2,"is_corresponding":false},{"id":425541,"name":"Hongyan Ma","orcid":null,"position":3,"is_corresponding":false},{"id":784352,"name":"Victoria M. Anderson","orcid":null,"position":4,"is_corresponding":false},{"id":588609,"name":"Ross D. Overacker","orcid":null,"position":5,"is_corresponding":false},{"id":422473,"name":"April L. Risinger","orcid":"0000-0002-4363-3268","position":6,"is_corresponding":false},{"id":588267,"name":"Sandra Loesgen","orcid":"0000-0003-1090-564X","position":7,"is_corresponding":false},{"id":30173,"name":"Peter J. Houghton","orcid":"0000-0002-2400-8184","position":8,"is_corresponding":false},{"id":422475,"name":"Robert H. Cichewicz","orcid":"0000-0003-0744-4117","position":9,"is_corresponding":false},{"id":422474,"name":"Susan L. Mooberry","orcid":"0000-0001-8575-2516","position":10,"is_corresponding":false},{"id":783815,"name":"Andrew J. Robles","orcid":"0000-0003-3447-0169","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:51:14.206397Z","pmid":"34944795","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":[]}