title: An off-on COX-2-specific fluorescent probe: targeting the Golgi apparatus of cancer cells.
abstract: Identifying cancer cells and quantifying cancer-related events in particular organelles in a rapid and sensitive fashion are important for early diagnosis and for studies on pathology and therapeutics of cancers. Herein a smart "off-on" cyclooxygenase-2-specific fluorescence probe (ANQ-IMC-6), able to report the presence of cancer cells and to image Golgi-related events, has been designed and evaluated. Cyclooxygenase-2 (COX-2) has been used as imaging target in the probe design, since this enzyme is a biomarker of virtually all cancer cell lines. In the free state in aqueous solution, ANQ-IMC-6 mainly exists in a folded conformation where probe fluorescence is quenched through photoinduced electron transfer between the fluorophore acenaphtho[1,2-b]quinoxaline (ANQ) and the recognition group, indomethacin (IMC). Fluorescence is turned on, by restraining the photoinduced electron transfer, when ANQ-IMC-6 is forced to adopt the unfolded state following binding to COX-2 in the Golgi apparatus of cancer cells. ANQ-IMC-6 provides high signal-to-background staining and has been successfully used to rapidly differentiate cancer cells from normal cells when using flow cytometry and one- and two-photon fluorescence microscopic imaging. Furthermore, ANQ-IMC-6 may be able to visualize dynamic changes of the Golgi apparatus during cancer cell apoptosis, with possible application to early diagnosis.
authors.affiliation: State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, Dalian 116024, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Jiangli
authors.initials: J
authors.lastname: Fan
authors.forename: Jingyun
authors.initials: J
authors.lastname: Wang
authors.forename: Shuangzhe
authors.initials: S
authors.lastname: Zhang
authors.forename: Bairui
authors.initials: B
authors.lastname: Dou
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Peng
mesh_terms: D000073:Acenaphthenes / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D061848:Optical Imaging / Q000379:methods; D011810:Quinoxalines / Q000737:chemistry / Q000378:metabolism
chemical_list: D000073:Acenaphthenes; D005456:Fluorescent Dyes; D011810:Quinoxalines; D051546:Cyclooxygenase 2; D007213:Indomethacin