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Induction of immunogenic cell death effect of licoricidin in cervical cancer cells by enhancing endoplasmic reticulum stress-mediated high mobility group box 1 expression.

Abstract
Licoricidin (LCD) is an activity compound of the roots of Glycyrrhiza uralensis, which has therapeutic efficacy, including anti-virus, anti-cancer, and enhanced immunity in Traditional Chinese Medicine. Herein, this study aimed to clarify the effect of LCD on cervical cancer cells. In the present study, we found that LCD significantly inhibited cell viability via inducing cell apoptosis and companies with cleaved-PARP protein expression and caspase-3/-9 activity. Cell viability was markedly reversed these effects by pan-caspase inhibitor Z-VAD-FMK treatment. Furthermore, we showed that LCD-induced ER (endoplasmic reticulum) stress triggers upregulating the protein level of GRP78 (Bip), CHOP, and IRE1α, and subsequently confirmed the mRNA level by quantitative real-time polymerase chain reaction. In addition, LCD exhibited the release of danger-associated molecular patterns from cervical cancer cells, such as the release of high-mobility group box 1 (HMGB1), secretion of ATP, and exposure of calreticulin (CRT) on the cell surface, which led to immunogenic cell death (ICD). These results provide a novel foundation that LCD induces ICD via triggering ER stress in human cervical cancer cells. LCD might be an ICD inducer of immunotherapy in progressive cervical cancer.
AuthorsPei-Ju Wu, Hui-Ling Chiou, Yi-Hsien Hsieh, Chia-Liang Lin, Hsiang-Lin Lee, I-Chun Liu, Tsung-Ho Ying
JournalEnvironmental toxicology (Environ Toxicol) Vol. 38 Issue 7 Pg. 1641-1650 (Jul 2023) ISSN: 1522-7278 [Electronic] United States
PMID37013980 (Publication Type: Journal Article)
Copyright© 2023 Wiley Periodicals LLC.
Chemical References
  • licoricidin
  • Endoribonucleases
  • HMGB1 Protein
  • Protein Serine-Threonine Kinases
  • Endoplasmic Reticulum Chaperone BiP
Topics
  • Female
  • Humans
  • Uterine Cervical Neoplasms
  • Endoribonucleases (pharmacology)
  • HMGB1 Protein (metabolism)
  • Immunogenic Cell Death
  • Cell Line, Tumor
  • Protein Serine-Threonine Kinases
  • Apoptosis
  • Endoplasmic Reticulum Chaperone BiP
  • Endoplasmic Reticulum Stress

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