title: Enzyme prodrug therapy designed to target L-methioninase to the tumor vasculature.
abstract: A new approach for enzyme prodrug therapy for cancer was tested using human endothelial cells and two breast cancer cell lines in vitro. The concept is to use the human annexin V protein to selectively target the enzyme L-methioninase to the tumor vasculature. The major finding was that enzyme prodrug treatment using the L-methioninase-annexin V fusion protein and selenomethionine as the prodrug over 3 days was shown to be lethal to the endothelial cells and the cancer cells, while having little or no effect with the prodrug but with no fusion protein present. Thus, this new approach appears promising.
authors.affiliation: Bioengineering Center, University of Oklahoma, Norman, USA.
authors.forename: Brent D
authors.initials: BD
authors.lastname: Van Rite
authors.forename: Yahya A
authors.initials: YA
authors.lastname: Lazrak
authors.forename: Magali L
authors.initials: ML
authors.lastname: Pagnon
authors.forename: Naveen R
authors.initials: NR
authors.lastname: Palwai
authors.forename: Luís F F
authors.initials: LF
authors.lastname: Neves
authors.forename: Peter S
authors.initials: PS
authors.lastname: McFetridge
authors.forename: Roger G
authors.initials: RG
authors.lastname: Harrison
mesh_terms: D017304:Annexin A5 / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D013437:Carbon-Sulfur Lyases / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D000432:Methanol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control; D016566:Organoselenium Compounds / Q000378:metabolism / Q000494:pharmacology; D011355:Prodrugs / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D012645:Selenomethionine / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D017304:Annexin A5; D016566:Organoselenium Compounds; D011355:Prodrugs; D011993:Recombinant Fusion Proteins; C019003:methaneselenol; D012645:Selenomethionine; D013437:Carbon-Sulfur Lyases; C021558:L-methionine gamma-lyase; D000432:Methanol