The GSK-3 inhibitor BIO promotes proliferation in mammalian cardiomyocytes

Chem Biol. 2006 Sep;13(9):957-63. doi: 10.1016/j.chembiol.2006.08.004.


The maintenance of self-renewal in stem cells appears to be distinct from the induction of proliferation of the terminally differentiated mammalian cardiomyocytes because it is believed that the latter are unable to divide. However, proliferation is a necessary step in both processes. Interestingly, the small molecule 6-bromoindirubin-3'-oxime (BIO) is the first pharmacological agent shown to maintain self-renewal in human and mouse embryonic stem cells. To determine whether a molecule that can maintain stem cell properties can also participate in controlling the proliferative capability of the highly differentiated cardiomyocytes, we examine the effect of BIO in postmitotic cardiac cells. Here, we show that BIO promotes proliferation in mammalian cardiomyocytes. Our demonstration of a second role for BIO suggests that the maintenance of stem cell self-renewal and the induction of proliferation in differentiated cardiomyocytes may share common molecular pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Cycle / drug effects
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors*
  • Indoles / pharmacology*
  • Male
  • Mitosis
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / drug effects
  • Oximes / pharmacology*
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Wnt Proteins / metabolism
  • beta Catenin / metabolism


  • 6-bromoindirubin-3'-oxime
  • Enzyme Inhibitors
  • Indoles
  • Oximes
  • Wnt Proteins
  • beta Catenin
  • Glycogen Synthase Kinase 3