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All-trans retinoic acid suppresses topoisomerase IIα through the proteasomal pathway

Xiaoting Li1, Yuan Li, Xin Shen

  • 1aDepartment of Nutrition and Food Safety, Nanjing Medical University bDepartment of Gynecology of the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Anti-Cancer Drugs
|May 7, 2015
PubMed

Insights

All-trans retinoic acid (ATRA) suppresses the anticancer target topoisomerase IIα protein levels in carcinoma cells. This mechanism involves proteasomal degradation, promoting cell differentiation.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Cancer Research

Background:

  • Topoisomerase IIα is a nuclear enzyme critical for DNA topology and cell differentiation.
  • It is a recognized anticancer target, with limited data on retinoid regulation.
  • All-trans retinoic acid (ATRA), a vitamin A metabolite, shows anticancer potential.

Purpose of the Study:

  • To investigate the relationship between ATRA and topoisomerase IIα.
  • To elucidate the mechanisms by which ATRA regulates topoisomerase IIα.
  • To explore the impact of this regulation on cell differentiation.

Main Methods:

  • Western blot and immunocytochemistry in human carcinoma cell lines.
  • Analysis of protein and mRNA expression levels.
  • Investigation of proteasome and lysosome degradation pathways.
  • Ubiquitination assays and cyclin D1 expression analysis.

Main Results:

  • ATRA suppressed topoisomerase IIα protein, not mRNA, in carcinoma cells.
  • ATRA induced topoisomerase IIα degradation via the proteasome pathway, involving ubiquitination.
  • Nuclear topoisomerase IIα repression by ATRA correlated with reduced cyclin D1 expression.
  • Knockdown of topoisomerase IIα enhanced cell differentiation, opposing overexpression effects.

Conclusions:

  • ATRA targets topoisomerase IIα for proteasomal degradation in cancer cells.
  • This ATRA-induced repression of topoisomerase IIα influences cell cycle and differentiation.
  • ATRA demonstrates potential anticancer benefits by modulating topoisomerase IIα and promoting cell differentiation.

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