Licochalcone A inhibits cell growth through the downregulation of the Hippo pathway via PES1 in cholangiocarcinoma cells

Environ Toxicol. 2022 Mar;37(3):564-573. doi: 10.1002/tox.23422. Epub 2021 Nov 30.

Abstract

Overexpression or activation of Yes-associated protein (YAP) is common in cancer cells. Thus, targeting YAP may be a strategy for cancer therapy. Licochalcone A (LicA) is a primary active compound of licorice root and is known to have medicinal effects, such as antioxidant, antibacterial, antiviral, and anticancer effects. However, the anticancer pharmacological mechanism of LicA has not been investigated in cholangiocarcinoma. In this study, we investigated the antiproliferative effect of LicA and the underlying molecular mechanism in HCCC-9810 and RBE human cholangiocarcinoma cells. Our experiments indicated that LicA suppressed the growth of cholangiocarcinoma cells through inactivation of the Hippo pathway. Pescadillo ribosomal biogenesis factor 1 (PES1) was notably upregulated and related to carcinogenesis. We also found that LicA suppressed the expression and nuclear localization of PES1, which was associated with the inhibition of YAP expression and transcriptional activity.

Keywords: Licochalcone A; cell proliferation; cholangiocarcinoma; hippo signaling; pescadillo ribosomal biogenesis factor 1.

MeSH terms

  • Bile Duct Neoplasms* / drug therapy
  • Bile Ducts, Intrahepatic
  • Cell Proliferation
  • Chalcones
  • Cholangiocarcinoma* / drug therapy
  • Down-Regulation
  • Hippo Signaling Pathway
  • Humans
  • RNA-Binding Proteins
  • Signal Transduction

Substances

  • Chalcones
  • PES1 protein, human
  • RNA-Binding Proteins
  • licochalcone A