Tanshinone IIA promotes cardiac differentiation and improves cell motility by modulating the Wnt/β‑catenin signaling pathway

Mol Med Rep. 2020 Sep;22(3):1839-1846. doi: 10.3892/mmr.2020.11272. Epub 2020 Jun 24.

Abstract

Although the cardiovascular pharmacological actions of Tanshinone IIA (TanIIA) have been extensively studied, research on its roles in cardiac regeneration is still insufficient. The present study employed the cardiac myoblast cell line H9c2 to evaluate the possible roles of TanIIA in cardiac regeneration. It was found that certain concentration of TanIIA inhibited cell proliferation by suppressing the expression of proteins related to the cell cycle [cyclin dependent kinase (CDK)4, CDK6 and cyclin D1] and proliferation [c‑Myc, octamer‑binding transcription factor 4 (Oct4) and proliferating cell nuclear antigen (PCNA)] without inducing apoptosis. In this process, the expression of cardiac troponin in the treated cells was significantly increased and the migration of the treated cells toward the wound area was significantly enhanced. Meanwhile, TanIIA inhibited the canonical signaling pathway through increasing the expression of glycogen synthase kinase 3β (GSK‑3β) and adenomatous polyposis coli (APC) and increased the expression of Wnt11 and Wnt5a in the noncanonical Wnt signaling pathway. Following β‑catenin agonist WAY‑262611 intervention, the effect of TanIIA on the promotion of cardiac differentiation and improved cell migration was significantly reduced. In conclusion, it was hypothesized that TanIIA could promote cardiac differentiation and improve cell motility by modulating the Wnt/β‑catenin signaling pathway. These results suggest that TanIIA may play beneficial roles in myocardial regeneration following stem cell transplantation.

Keywords: Tanshinone iia; H9c2 cells; cardiac differentiation; cell motility; Wnt/β-catenin signaling.

MeSH terms

  • Abietanes / pharmacology*
  • Animals
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cyclin-Dependent Kinase 6 / metabolism
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Rats
  • Wnt Signaling Pathway / drug effects*

Substances

  • Abietanes
  • Ccnd1 protein, rat
  • tanshinone
  • Cyclin D1
  • Cdk4 protein, rat
  • Cdk6 protein, rat
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6