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

May 5, 2017Journal of biological rhythms

Internal Circadian Clock Gene Bmal1 May Affect Glioblastoma's Sensitivity to Temozolomide

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Abstract

Daily rhythms in glioblastoma cells influence the effectiveness of the chemotherapy drug temozolomide (TMZ).

  • Circadian rhythms were observed in both human and mouse glioblastoma cells.
  • The timing of TMZ administration affected the sensitivity of murine GBM tumor cells to the drug.
  • The greatest DNA damage, activation of cell death, and growth inhibition occurred when TMZ was given near the peak expression of the core clock gene Bmal1.
  • Deleting the Bmal1 gene eliminated circadian rhythms in gene expression and reduced the effectiveness of TMZ.
  • These findings suggest that the natural daily rhythms in tumor cells may influence chemotherapy outcomes.

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