Acetyl-11-keto-beta-boswellic acid inhibits cell proliferation and growth of oral squamous cell carcinoma via RAB7B-mediated autophagy

Toxicol Appl Pharmacol. 2024 Apr:485:116906. doi: 10.1016/j.taap.2024.116906. Epub 2024 Mar 19.

Abstract

Natural products can overcome the limitations of conventional chemotherapy. Acetyl-11-keto-beta-boswellic acid (AKBA) as a natural product extracted from frankincense, exhibited chemotherapeutic activities in different cancers. However, whether AKBA exerts inhibiting effect of oral squamous cell carcinoma (OSCC) cells growth and the mechanism need to be explored. We attempted to investigate the therapeutic effects of AKBA against OSCC and explore the mechanism involved. Here we attempt to disclose the cell-killing effect of AKBA on OSCC cell lines and try to figure out the specifical pathway. The presence of increase autophagosome and the production of mitochondrial reactive oxygen species were confirmed after the application of AKBA on OSCC cells, and RAB7B inhibition enhanced autophagosome accumulation. Though the increase autophagosome was detected induced by AKBA, autophagic flux was inhibited as the failure fusion of autophagosome and lysosome. Cal27 xenografts were established to verify the role of anti-OSCC cells of AKBA in vivo. Based above findings, we speculate that natural product AKBA suppresses OSCC cells growth via RAB7B-mediated autophagy and may serve as a promising strategy for the therapy of OSCC.

Keywords: Acetyl-11-keto-beta-boswellic acid; Autophagy; Natural products; OSCC; RAB7B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy* / drug effects
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude*
  • Mouth Neoplasms* / drug therapy
  • Mouth Neoplasms* / metabolism
  • Mouth Neoplasms* / pathology
  • Reactive Oxygen Species / metabolism
  • Triterpenes* / pharmacology
  • Xenograft Model Antitumor Assays*
  • rab GTP-Binding Proteins* / metabolism
  • rab7 GTP-Binding Proteins*

Substances

  • Triterpenes
  • rab7 GTP-Binding Proteins
  • rab GTP-Binding Proteins
  • acetyl-11-ketoboswellic acid
  • rab7 GTP-binding proteins, human
  • Reactive Oxygen Species