Caffeine Sensitizes U87-MG Human Glioblastoma Cells to Temozolomide through Mitotic Catastrophe by Impeding G2 Arrest.
Temozolomide (TMZ) is the first-line chemotherapeutic agent in the treatment of glioblastoma multiforme (GBM). Despite its cytotoxic effect, TMZ also induces cell cycle arrest that may lead to the development of chemoresistance and eventual tumor recurrence. Caffeine, a widely consumed neurostimulan...
| Published in: | BioMed Research International Vol. 2018; pp. 1 - 11 |
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| Main Authors: | , , , , |
| Format: | pictorial research tables/charts Journal Article |
| Published: |
Wiley-Blackwell
6/28/2018
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=130381415&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 130381415 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 6/28/2018 vid: 2018 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 130381415 130381415 130381415 10.1155/2018/5364973 130381415 ppf: 1 ppct: 10 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Caffeine Sensitizes U87-MG Human Glioblastoma Cells to Temozolomide through Mitotic Catastrophe by Impeding G2 Arrest. aug: au: Li, Ning Zhang, Pingde Kiang, Karrie Mei Yee Cheng, Yin Stephen Leung, Gilberto Ka Kit affil: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong sug: subj: Caffeine Pharmacodynamics Temozolomide Pharmacodynamics Glioma Cell Line, Tumor Drug Effects Cell Physiology Drug Effects Drug Combinations Human Signal Transduction Drug Effects Cell Proliferation Drug Effects Phosphorylation Drug Effects Gene Expression Drug Effects Apoptosis Drug Effects ab: Temozolomide (TMZ) is the first-line chemotherapeutic agent in the treatment of glioblastoma multiforme (GBM). Despite its cytotoxic effect, TMZ also induces cell cycle arrest that may lead to the development of chemoresistance and eventual tumor recurrence. Caffeine, a widely consumed neurostimulant, shows anticancer activities and is reported to work synergistically with cisplatin and camptothecin. The present study aimed to investigate the effects and the mechanisms of action of caffeine used in combination with TMZ in U87-MG GBM cells. As anticipated, TMZ caused DNA damage mediated by the ATM/p53/p21 signaling pathway and induced significant G2 delay. Concurrent treatment with caffeine repressed proliferation and lowered clonogenic capacity on MTT and colony formation assays, respectively. Mechanistic study showed that coadministration of caffeine and TMZ suppressed the phosphorylation of ATM and p53 and downregulated p21 expression, thus releasing DNA-damaged cells from G2 arrest into premature mitosis. Cell cycle analysis demonstrated that the proportion of cells arrested in G2 phase decreased when caffeine was administered together with TMZ; at the same time, the amount of cells with micronucleation and multipolar spindle poles increased, indicative of enhanced mitotic cell death. Pretreatment of cells with caffeine further enhanced mitotic catastrophe development in combined treatment and sensitized cells to apoptosis when followed by TMZ alone. In conclusion, our study demonstrated that caffeine enhanced the efficacy of TMZ through mitotic cell death by impeding ATM/p53/p21-mediated G2 arrest. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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