Pristimerin induces apoptosis and tumor inhibition of oral squamous cell carcinoma through activating ROS-dependent ER stress/Noxa pathway

Phytomedicine. 2021 Nov;92:153723. doi: 10.1016/j.phymed.2021.153723. Epub 2021 Aug 19.

Abstract

Background: Pristimerin (Pri), a natural quinone methide triterpenoid isolated from Celastraceae and Hippocrateaceae, exhibits potent antitumor activity against various cancers. However, the mechanism of apoptosis induction by Pri in oral squamous cell carcinoma (OSCC) and its anti-OSCC effect in vivo has not been widely studied.

Purpose: This study aimed to investigate the anti-OSCC activities of Pri in vitro and in vivo and addressed the potential mechanisms of Pri-induced apoptosis.

Methods: The effects of Pri on OSCC cells were analyzed by cell viability, colony formation and flow cytometry assays. Western blotting and qRT-PCR assays were chosen to detect the expression of proteins and genes. The anti-OSCC efficacy of Pri in vivo was evaluated by CAL-27 xenografts.

Results: We showed that Pri inhibited the proliferation of human OSCC cell lines. Additionally, Pri induced apoptosis by upregulating Noxa expression. Furthermore, Pri treatment triggered excessive endoplasmic reticulum (ER) stress activation and subsequently induced c-Jun N-terminal kinase (JNK) signaling. ROS scavengers and ER stress inhibitors significantly attenuated Pri-induced OSCC cell apoptosis. Finally, Pri suppressed tumor growth in CAL-27 xenografts, accompanied ER stress activation and cell apoptosis.

Conclusion: These results reveal that Pri suppressed tumor growth and triggered cell apoptosis through ER stress activation in OSCC cells and xenografts, suggesting that Pri may serve as a therapeutic agent for OSCC.

Keywords: Apoptosis; ER stress; Noxa; OSCC; Pri.

MeSH terms

  • Apoptosis
  • Carcinoma, Squamous Cell* / drug therapy
  • Cell Line, Tumor
  • Cell Proliferation
  • Endoplasmic Reticulum Stress
  • Head and Neck Neoplasms*
  • Humans
  • Mouth Neoplasms* / drug therapy
  • Pentacyclic Triterpenes
  • Reactive Oxygen Species
  • Squamous Cell Carcinoma of Head and Neck
  • Triterpenes* / pharmacology

Substances

  • Pentacyclic Triterpenes
  • Reactive Oxygen Species
  • Triterpenes
  • celastrol methyl ester