Licochalcone A induces endoplasmic reticulum stress-mediated apoptosis of endometrial cancer cells via upregulation of GRP78 expression

Environ Toxicol. 2024 May;39(5):2961-2969. doi: 10.1002/tox.24156. Epub 2024 Feb 2.

Abstract

Licochalcone A (LicA), a natural compound extracted from licorice root, has been shown to exert a variety of anticancer activities. Whether LicA has such effects on endometrial cancer (EMC) is unclear. This study aims to investigate the antitumor effects of LicA on EMC. Our results show that LicA significantly reduced the viability and induced apoptosis of EMC cells and EMC-7 cells from EMC patients. LicA was also found to induce endoplasmic reticulum (ER) stress, leading to increased expression of ER-related proteins (GRP78/PERK/IRE1α/CHOP) in EMC cell lines. Suppression of GRP78 expression in human EMC cells treated with LicA significantly attenuated the effects of LicA, resulting in reduced ER-stress mediated cell apoptosis and decreased expression of ER- and apoptosis-related proteins. Our findings demonstrate that LicA induces apoptosis in EMC cells through the GRP78-mediated ER-stress pathway, emphasizing the potential of LicA as an anticancer therapy for EMC.

Keywords: GRP78; apoptosis; endometrial cancer; endoplasmic reticulum; licochalcone A.

MeSH terms

  • Apoptosis
  • Apoptosis Regulatory Proteins / metabolism
  • Chalcones*
  • Endometrial Neoplasms*
  • Endoplasmic Reticulum Chaperone BiP*
  • Endoplasmic Reticulum Stress
  • Endoribonucleases / metabolism
  • Endoribonucleases / pharmacology
  • Female
  • Humans
  • Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction
  • Transcription Factor CHOP / metabolism
  • Up-Regulation

Substances

  • licochalcone A
  • Endoplasmic Reticulum Chaperone BiP
  • Endoribonucleases
  • Protein Serine-Threonine Kinases
  • Apoptosis Regulatory Proteins
  • Transcription Factor CHOP
  • Chalcones