title: In vitro assessment of novel transcription inhibitors and topoisomerase poisons in rhabdomyosarcoma cell lines.
abstract: OBJECTIVE
  Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Current chemotherapy regimes include the topoisomerase II poison etoposide and the transcription inhibitor actinomycin D. Poor clinical response necessitate identification of new agents to improve patient outcomes.
  
  
  METHODS
  We assessed the in vitro cytotoxicity (MTT assay) of DNA intercalating agents in five established human RMS cell lines. These include novel classes of transcription inhibitors and topoisomerase poisons, previously shown to have potential as anti-cancer agents.
  
  
  RESULTS
  Amongst the former agents, bisintercalating bis(9-aminoacridine-4-carboxamides) linked through the 9-position, and bis(phenazine-1-carboxamides) linked via their side chains, are compared with established transcription inhibitors. Amongst the latter, monofunctional acridine-4-carboxamides related to N-[2-(dimethylamino)ethyl]acridine-4-carboxamide, DACA, are compared with established topoisomerase poisons.
  
  
  CONCLUSIONS
  Our findings specifically highlight the topoisomerase poison 9-amino-DACA, its 5-methylsulphone derivative, AS-DACA, and the bis(phenazine-1-carboxamide) transcription inhibitor MLN944/XR5944, currently in phase I trial, as candidates for further research into new agents for the treatment of RMS.
authors.affiliation: The Tumour Bank, Oncology Research Unit, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW 2145, Australia.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Wolf
authors.forename: Laurence P G
authors.initials: LP
authors.lastname: Wakelin
authors.forename: Zhicong
authors.initials: Z
authors.lastname: He
authors.forename: Bernard W
authors.initials: BW
authors.lastname: Stewart
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Catchpoole
mesh_terms: D000166:Acridines / Q000494:pharmacology; D000609:Aminoacridines / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D010619:Phenazines / Q000494:pharmacology; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000378:metabolism; D018232:Rhabdomyosarcoma, Alveolar / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D018233:Rhabdomyosarcoma, Embryonal / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D059003:Topoisomerase Inhibitors
chemical_list: D000166:Acridines; D000609:Aminoacridines; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D010619:Phenazines; D059003:Topoisomerase Inhibitors; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II