Targeted Detection of Cyclooxygenase-1 in Ovarian Cancer.

Autor: Malerba P; A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute of Chemical Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 United States.; Department of Pharmacy and Pharmaceutical Sciences, University of Bari 'A. Moro', Via Orabona 4, 70125 Bari, Italy., Crews BC; A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute of Chemical Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 United States., Ghebreselasie K; A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute of Chemical Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 United States., Daniel CK; A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute of Chemical Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 United States., Jashim E; A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute of Chemical Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 United States., Aleem AM; A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute of Chemical Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 United States., Salam RA; A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute of Chemical Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 United States.; Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130 United States., Marnett LJ; A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute of Chemical Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 United States., Uddin MJ; A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute of Chemical Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 United States.
Jazyk: angličtina
Zdroj: ACS medicinal chemistry letters [ACS Med Chem Lett] 2019 Jul 24; Vol. 11 (10), pp. 1837-1842. Date of Electronic Publication: 2019 Jul 24 (Print Publication: 2020).
DOI: 10.1021/acsmedchemlett.9b00280
Abstrakt: Overexpression of cyclooxygenase-1 (COX-1) is associated with the initiation and progression of ovarian cancer, and targeted imaging of COX-1 is a promising strategy for early detection of this disease. We report the discovery of N -[(5-carboxy-X-rhodaminyl)but-4-yl]-3-(1-(4-methoxyphenyl)-5-( p -tolyl)-1 H -pyrazol-3-yl)propenamide (CMP) as the first COX-1-targeted optical agent for imaging of ovarian cancer. CMP exhibits light emission at 604 nm (λ max ), thereby minimizing tissue autofluorescence interference. In both purified enzyme and COX-1-expressing human ovarian adenocarcinoma (OVCAR-3) cells, CMP inhibits COX-1 at low nanomolar potencies (IC 50 = 94 and 44 nM, respectively). CMP's selective binding to COX-1 in OVCAR-3 cells was visualized microscopically as intense intracellular fluorescence. In vivo optical imaging of xenografts in athymic nude mice revealed COX-1-dependent accumulation of CMP in COX-1-expressing mouse ovarian surface epithelial carcinoma (ID8-NGL) and OVCAR-3 cells. These results establish proof-of-principle for the feasibility of targeting COX-1 in the development of new imaging and therapeutic strategies for ovarian cancer.
Competing Interests: The authors declare no competing financial interest.
Databáze: MEDLINE
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