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Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma

Slat, Emily A. ; Sponagel, Jasmin ; Marpegan, Luciano ; Simon, Tatiana ; Kfoury, Najla ; Kim, Albert ; Binz, Andrea ; Herzog, Erik D. ; Rubin, Joshua B.

Journal of biological rhythms, 2017-04, Vol.32 (2), p.121-129 [Periódico revisado por pares]

Los Angeles, CA: SAGE Publications

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Título:
Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma
Autor: Slat, Emily A. ; Sponagel, Jasmin ; Marpegan, Luciano ; Simon, Tatiana ; Kfoury, Najla ; Kim, Albert ; Binz, Andrea ; Herzog, Erik D. ; Rubin, Joshua B.
Assuntos: Activation ; Alkylation ; Animals ; Antineoplastic Agents, Alkylating - pharmacology ; Apoptosis ; Apoptosis - drug effects ; ARNTL Transcription Factors - deficiency ; ARNTL Transcription Factors - genetics ; ARNTL Transcription Factors - metabolism ; BMAL1 protein ; Brain ; Cancer ; Cell Line, Tumor ; Cell Proliferation ; Circadian rhythm ; Circadian Rhythm - drug effects ; Circadian rhythms ; Clinical trials ; CLOCK protein ; Clonal deletion ; Cytotoxicity ; Dacarbazine - analogs & derivatives ; Dacarbazine - pharmacology ; Deoxyribonucleic acid ; DNA ; DNA damage ; DNA Repair - drug effects ; Drug Administration Schedule ; Gene deletion ; Gene expression ; Gene Expression Regulation, Neoplastic ; Glioblastoma ; Glioblastoma - drug therapy ; Humans ; In vitro methods and tests ; Inhibition ; Medical research ; Mice ; Optimization ; Period Circadian Proteins - metabolism ; Sensitivity ; Studies ; Temozolomide ; Toxicity ; Tumor cells ; Tumors
É parte de: Journal of biological rhythms, 2017-04, Vol.32 (2), p.121-129
Notas: These authors contributed equally.
Descrição: The safety and efficacy of chemotherapeutics can vary as a function of the time of their delivery during the day. This study aimed to improve the treatment of glioblastoma (GBM), the most common brain cancer, by testing whether the efficacy of the DNA alkylator temozolomide (TMZ) varies with the time of its administration. We found cell-intrinsic, daily rhythms in both human and mouse GBM cells. Circadian time of treatment affected TMZ sensitivity of murine GBM tumor cells in vitro. The maximum TMZ-induced DNA damage response, activation of apoptosis, and growth inhibition occurred near the daily peak in expression of the core clock gene Bmal1. Deletion of Bmal1 (Arntl) abolished circadian rhythms in gene expression and TMZ-induced activation of apoptosis and growth inhibition. These data indicate that tumor cell-intrinsic circadian rhythms are common to GBM tumors and can regulate TMZ cytotoxicity. Optimization of GBM treatment by timing TMZ administration to daily rhythms should be evaluated in prospective clinical trials.
Editor: Los Angeles, CA: SAGE Publications
Idioma: Inglês

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Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma

Slat, Emily A. ; Sponagel, Jasmin ; Marpegan, Luciano ; Simon, Tatiana ; Kfoury, Najla ; Kim, Albert ; Binz, Andrea ; Herzog, Erik D. ; Rubin, Joshua B.

Los Angeles, CA: SAGE Publications

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