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Status: Bibliographieeintrag

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Verfasst von:Schott, Sarah [VerfasserIn]   i
 Brüning, Ansgar [VerfasserIn]   i
Titel:Induction of apoptosis in cervical cancer cells by the duplex drug 5-FdU-ECyd, coupling 2'-deoxy-5-fluorouridine and 3'-C-ethinylcytidine
Verf.angabe:Sarah Schott, Ansgar Brüning
E-Jahr:2014
Jahr:30 August 2014
Umfang:7 S.
Fussnoten:Gesehen am 04.12.2020
Titel Quelle:Enthalten in: Gynecologic oncology
Ort Quelle:Orlando, Fla. : Academic Press, 1972
Jahr Quelle:2014
Band/Heft Quelle:135(2014), 2, Seite 342-348
ISSN Quelle:1095-6859
Abstract:OBJECTIVE: Therapeutic options are limited for patients with advanced cervical cancer, and more effective drugs with favorable side-effect profiles are needed. We developed a nucleoside analogue duplex drug (5-FdU-ECyd), in which the DNA synthesis inhibitor 5-fluorodeoxyuridine is coupled to the RNA synthesis inhibitor 3'-C-ethinylcytidine. We therefore aimed to test its efficacy in cervical carcinoma cells in vitro and to establish its mechanism of action. - METHODS: The cytotoxic effects of 5-FdU-ECyd on cervical cancer cells were assessed using the MTT assay, clonality assays, FACScan analysis, and its effect on cancer cell spheroids. Mechanisms of cell death were analyzed by Western blotting for apoptosis and autophagy pathways and mitochondrial membrane potential. - RESULTS: HeLa, CaSki, SiHa, and Me180 cervical cancer cells were highly sensitive to 5-FdU-ECyd in both 2- and 3-dimensional cancer models. The cell death induced by 5-FdU-ECyd was associated with characteristic morphological and biochemical signs of apoptosis, including nuclear chromatin condensation and fragmentation, PARP cleavage, and a breakdown in mitochondrial membrane potential. 5-FdU-ECyd treatment led to an early S-phase arrest and drastically reduced expression of the anti-apoptosis protein Mcl-1 and increased signaling via the JNK and p38 MAPK pathways. - CONCLUSIONS: 5-FdU-ECyd is highly cytotoxic in cervical cancer cells and exploits apoptosis pathways that might be specific to cancer, but not normal cells. 5-FdU-ECyd might represent a new chemotherapeutic option for patients with advanced or treatment refractory cervical cancer.
DOI:doi:10.1016/j.ygyno.2014.08.034
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1016/j.ygyno.2014.08.034
 DOI: https://doi.org/10.1016/j.ygyno.2014.08.034
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Antineoplastic Agents
 Apoptosis
 Apoptotic pathway
 Carcinoma, Squamous Cell
 Cell Cycle Checkpoints
 Cell Line, Tumor
 Cervical cancer
 Cytotoxic 5-FdU-ECyd conjugate
 Drug Screening Assays, Antitumor
 Female
 HeLa Cells
 Humans
 Membrane Potential, Mitochondrial
 Oligonucleotides
 Uterine Cervical Neoplasms
K10plus-PPN:1742093574
Verknüpfungen:→ Zeitschrift

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