دورية أكاديمية
أعرض في EDS

Delineating the Switch between Senescence and Apoptosis in Cervical Cancer Cells under Ciclopirox Treatment.

التفاصيل البيبلوغرافية
العنوان: Delineating the Switch between Senescence and Apoptosis in Cervical Cancer Cells under Ciclopirox Treatment.
المؤلفون: Herrmann AL; Molecular Therapy of Virus-Associated Cancers, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany., Kuhn BJ; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany.; Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Holzer A; Molecular Therapy of Virus-Associated Cancers, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Krijgsveld J; Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.; Medical Faculty, Heidelberg University, 69120 Heidelberg, Germany., Hoppe-Seyler K; Molecular Therapy of Virus-Associated Cancers, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Hoppe-Seyler F; Molecular Therapy of Virus-Associated Cancers, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
المصدر: Cancers [Cancers (Basel)] 2021 Oct 05; Vol. 13 (19). Date of Electronic Publication: 2021 Oct 05.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101526829 Publication Model: Electronic Cited Medium: Print ISSN: 2072-6694 (Print) Linking ISSN: 20726694 NLM ISO Abbreviation: Cancers (Basel) Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مستخلص: The iron-chelating drug ciclopirox (CPX) may possess therapeutic potential for cancer treatment, including cervical cancer. As is observed for other chemotherapeutic drugs, CPX can induce senescence or apoptosis in cervical cancer cells which could differently affect their therapy response. The present study aims to gain insights into the determinants which govern the switch between senescence and apoptosis in cervical cancer cells. We performed proteome analyses, proliferation studies by live-cell imaging and colony formation assays, senescence and apoptosis assays, and combination treatments of CPX with inhibitors of oxidative phosphorylation (OXPHOS) or glycolysis. We found that CPX downregulates OXPHOS factors and facilitates the induction of apoptosis under limited glucose availability, an effect which is shared by classical OXPHOS inhibitors. Under increased glucose availability, however, CPX-induced apoptosis is prevented and senescence is induced, an activity which is not exerted by classical OXPHOS inhibitors, but by other iron chelators. Moreover, we show that the combination of CPX with glycolysis inhibitors blocks cervical cancer proliferation in a synergistic manner. Collectively, our results reveal that the phenotypic response of cervical cancer cells towards CPX is strongly dependent on glucose availability, link the pro-apoptotic and pro-senescent activities of CPX to its bifunctionality as an OXPHOS inhibitor and iron chelator, respectively, and provide a rationale for combining CPX with glycolysis inhibitors.
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فهرسة مساهمة: Keywords: apoptosis; cervical cancer; human papillomavirus; senescence; therapy
تواريخ الأحداث: Date Created: 20211013 Latest Revision: 20211016
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8508512
DOI: 10.3390/cancers13194995
PMID: 34638479
قاعدة البيانات: MEDLINE
الوصف
تدمد:2072-6694
DOI:10.3390/cancers13194995