title: Programmed activation of cancer cell apoptosis: A tumor-targeted phototherapeutic topoisomerase I inhibitor.
abstract: We report here a tumor-targeting masked phototherapeutic agent 1 (PT-1). This system contains SN-38-a prodrug of the topoisomerase I inhibitor irinotecan. Topoisomerase I is a vital enzyme that controls DNA topology during replication, transcription, and recombination. An elevated level of topoisomerase I is found in many carcinomas, making it an attractive target for the development of effective anticancer drugs. In addition, PT-1 contains both a photo-triggered moiety (nitrovanillin) and a cancer targeting unit (biotin). Upon light activation in cancer cells, PT-1 interferes with DNA re-ligation, diminishes the expression of topoisomerase I, and enhances the expression of inter alia mitochondrial apoptotic genes, death receptors, and caspase enzymes, inducing DNA damage and eventually leading to apoptosis. In vitro and in vivo studies showed significant inhibition of cancer growth and the hybrid system PT-1 thus shows promise as a programmed photo-therapeutic ("phototheranostic").
authors.affiliation: Department of Chemistry, Korea University, Seoul 136-701, Korea.
authors.forename: Weon Sup
authors.initials: WS
authors.lastname: Shin
authors.affiliation: Department of Biotechnology, Laboratory of Stem Cells and Tissue Regeneration, College of Life Sciences &Biotechnology, Korea University, Seoul 136-713, Republic of Korea.
authors.forename: Jiyou
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Chemistry, Korea University, Seoul 136-701, Korea.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Biotechnology, Laboratory of Stem Cells and Tissue Regeneration, College of Life Sciences &Biotechnology, Korea University, Seoul 136-713, Republic of Korea.
authors.forename: Gyung Gyu
authors.initials: GG
authors.lastname: Lee
authors.affiliation: Department of Chemistry, University of Texas at Austin, Austin, TX 78712-1224, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Sessler
authors.affiliation: Department of Biotechnology, Laboratory of Stem Cells and Tissue Regeneration, College of Life Sciences &Biotechnology, Korea University, Seoul 136-713, Republic of Korea.
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Chemistry, Korea University, Seoul 136-701, Korea.
authors.forename: Jong Seung
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D000077146:Irinotecan; D007834:Lasers; D008807:Mice, Inbred BALB C; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D011355:Prodrugs / Q000138:chemical synthesis / Q000494:pharmacology*; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D011355:Prodrugs; D059004:Topoisomerase I Inhibitors; D000077146:Irinotecan; D020169:Caspases; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin