<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "The Effects of Iron Chelators on the Phenotype of HPV-Positive Cervical Cancer cells"^^ . "Oncogenic human papillomavirus (HPV) types are major human carcinogens. Sustained expression of the viral E6 and E7 oncogenes is essential for the malignant growth of HPV-positive cancer cells. Moreover, cancer cells typically exhibit metabolic alterations. Surprisingly little is known about the relation between the HPV oncogenes and the cellular iron metabolism although it is increasingly recognised to be linked to tumourigenesis. Thus, the overall aim of the presented studies was to investigate the crosstalk between oncogenic HPVs and the iron metabolism of their tumourigenic host cells. \r\nInterestingly, treatment of HPV-positive cervical cancer cells with the iron chelators deferoxamine (DFO) or ciclopirox (CPX) strongly suppresses expression of the viral E6/E7 oncogenes, suggesting therapeutic potential for these agents. Further detailed work was focused on CPX since (in contrast to DFO) this drug can be applied topically and thus could be suitable for the treatment of HPV-induced (pre)neoplasias. It was found that CPX efficiently blocks cellular proliferation in both 2D and 3D cell culture, induces cell cycle arrest in the G1 and S phase and ultimately leads to cellular senescence. Both E6/E7 repression and senescence are a consequence of iron deprivation since they can be prevented by excess iron. Notably, although mTORC1 signalling is widely believed to be required for senescence induction, the pro-senescent activity of CPX is independent of mTORC1 signalling. Proteome analyses revealed candidate proteins which might be involved in the CPX-induced growth arrest and senescence. Moreover, prolonged treatment of HPV-positive cervical cancer cells with CPX results in apoptosis which is observable under both normoxic and hypoxic conditions. Since CPX exerts pro-apoptotic effects also under hypoxia, it could be used in combination with radio- and chemotherapy which both are typically less active against hypoxic tumour cells.\r\nTaken together, these results reveal that HPV oncogene expression is very sensitive to iron deprivation. CPX could be a particularly promising agent for the treatment of HPV-positive cancers since it represses E6/E7, induces senescence and apoptosis under normoxic conditions and can also eliminate hypoxic cells which pose a major problem for the efficacy of anti-cancer drugs in the clinic."^^ . "2019" . . . . . . . "Julia Alexandra"^^ . "Braun"^^ . "Julia Alexandra Braun"^^ . . . . . . "The Effects of Iron Chelators on the Phenotype of HPV-Positive Cervical Cancer cells (PDF)"^^ . . . "Doktorarbeit_Julia Braun_final_PDFA.pdf"^^ . . . "The Effects of Iron Chelators on the Phenotype of HPV-Positive Cervical Cancer cells (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "The Effects of Iron Chelators on the Phenotype of HPV-Positive Cervical Cancer cells (Other)"^^ . . . . . . "preview.jpg"^^ . . . "The Effects of Iron Chelators on the Phenotype of HPV-Positive Cervical Cancer cells (Other)"^^ . . . . . . "medium.jpg"^^ . . . "The Effects of Iron Chelators on the Phenotype of HPV-Positive Cervical Cancer cells (Other)"^^ . . . . . . "small.jpg"^^ . . . "The Effects of Iron Chelators on the Phenotype of HPV-Positive Cervical Cancer cells (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #25814 \n\nThe Effects of Iron Chelators on the Phenotype of HPV-Positive Cervical Cancer cells\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .