Circadian regulation of mouse topoisomerase I gene expression by glucocorticoid hormones

Yukako Kuramoto, Koujirou Hata, Koyanagi Satoru, Shigehiro Ohdo, Hiroshi Shimeno, Shinji Soeda

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Because glucocorticoid hormones modulate various biological processes, the endogenous rhythm of their secretion is thought to be an important factor affecting the efficacy and/or toxicity of many drugs. Topoisomerase I (Topo I) is a nuclear target of the anticancer drug camptothecin (CPT). In this study, we demonstrate that Topo I expression in tumor-bearing mice and the efficacy of CPT on the tumor are affected by the 24-h variation in circulating glucocorticoid levels. A single administration of corticosterone (CORT) to the tumor-bearing mice resulted in a significant increase in Topo I mRNA levels not only in the tumor masses but also in other healthy tissues such as liver and skeletal muscle. The CORT-induced increase in Topo I mRNA was suppressed by pretreating the mice with RU486, a glucocorticoid receptor antagonist. Significant 24-h oscillations in the Topo I mRNA levels were observed in the tumor and healthy liver without exogenous CORT, and were eliminated by adrenalectomy of the mice. This result suggests that endogenous glucocorticoid hormones are involved in the circadian regulation of Topo I gene expression. Furthermore, the anti-tumor efficacy of the Topo I inhibitor CPT-11 on the tumor-bearing mice was enhanced by administering the drug at the time when the Topo I activity was increased. Our present results demonstrate that glucocorticoid is involved in the 24-h oscillation mechanism of Topo I gene expression and suggest that monitoring the circadian rhythm in Topo I activity is useful for choosing the most appropriate time of day to administer of Topo I inhibitors.

Original languageEnglish
Pages (from-to)1155-1161
Number of pages7
JournalBiochemical Pharmacology
Volume71
Issue number8
DOIs
Publication statusPublished - Apr 14 2006

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Type I DNA Topoisomerase
Gene expression
Glucocorticoids
Hormones
Tumors
Gene Expression
Bearings (structural)
Corticosterone
Neoplasms
Topoisomerase I Inhibitors
Camptothecin
irinotecan
Liver
Messenger RNA
Pharmaceutical Preparations
Biological Phenomena
Adrenalectomy
Glucocorticoid Receptors
Gene Expression Profiling
Circadian Rhythm

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

Cite this

Circadian regulation of mouse topoisomerase I gene expression by glucocorticoid hormones. / Kuramoto, Yukako; Hata, Koujirou; Satoru, Koyanagi; Ohdo, Shigehiro; Shimeno, Hiroshi; Soeda, Shinji.

In: Biochemical Pharmacology, Vol. 71, No. 8, 14.04.2006, p. 1155-1161.

Research output: Contribution to journalArticle

Kuramoto, Yukako ; Hata, Koujirou ; Satoru, Koyanagi ; Ohdo, Shigehiro ; Shimeno, Hiroshi ; Soeda, Shinji. / Circadian regulation of mouse topoisomerase I gene expression by glucocorticoid hormones. In: Biochemical Pharmacology. 2006 ; Vol. 71, No. 8. pp. 1155-1161.
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