Rottlerin inhibits cell growth, induces apoptosis and cell cycle arrest, and inhibits cell invasion in human hepatocellular carcinoma

Mol Med Rep. 2018 Jan;17(1):459-464. doi: 10.3892/mmr.2017.7924. Epub 2017 Oct 27.

Abstract

Rottlerin, a polyphenolic compound, has been demonstrated to exhibit antitumor activity in various types of human cancer. Several studies have revealed that rottlerin exerts its anticancer function through PKC‑dependent and independent pathways. The transcriptional co‑activator with PDZ‑binding motif (TAZ) oncopreotein is an important molecule in regulation of the Hippo pathway in human cancer. The present study investigated whether rottlerin has a tumor suppressive role via inhibiting the expression of TAZ, using cell viability assay, apoptosis and cell cycle analyses, western blot analysis and Tanswell invasion assay. The results demonstrated that rottlerin suppressed cell growth, triggered cell apoptosis and induced cell cycle arrest. In addition, rottlerin inhibited cell migration and invasion in hepatocellular carcinoma (HCC) cells. Mechanistically, the results demonstrated that rottlerin exerted its antitumor activity partly through the inhibition of TAZ. In addition, the depletion of TAZ led to inhibited cell growth and invasion, whereas the overexpression of TAZ enhanced cell growth and invasion in the HCC cells. Taken together, these findings indicated that the inhibition of TAZ by rottlerin may be a novel strategy for treating HCC.

MeSH terms

  • Acetophenones / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Benzopyrans / pharmacology*
  • Carcinoma, Hepatocellular
  • Cell Cycle Checkpoints / drug effects*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Humans
  • Liver Neoplasms

Substances

  • Acetophenones
  • Antineoplastic Agents
  • Benzopyrans
  • rottlerin