Cyclodextrin Conjugated α-Bisabolol Suppresses FAK Phosphorylation and Induces Apoptosis in Pancreatic Cancer

Anticancer Res. 2023 Mar;43(3):1009-1016. doi: 10.21873/anticanres.16245.

Abstract

Background/aim: α-Bisabolol is an essential oil component extracted from plants, such as chamomile. We have previously reported that α-bisabolol suppressed proliferation, invasion, and motility of pancreas cancer. Cyclodextrin improved the solubility of α-bisabolol, therefore it enabled to administer intravenously. The aim of this study was to clarify the effect of cyclodextrin conjugated α-bisabolol (CD-BSB) and the signals pathways associated with α-bisabolol for pancreatic cancer.

Materials and methods: Human pancreatic cancer cell lines were treated with or without CD-BSB. Cytomorphology and apoptosis were assessed in these treated groups. In addition, several phosphorylated proteins were analyzed to clarify the signal pathway concerning CD-BSB. In subcutaneous xenograft model, tumor volume and Ki-67 expression were evaluated among Control (untreated), CD-BSB, or Gemcitabine (GEM).

Results: CD-BSB significantly changed cytomorphology and induced apoptosis in pancreatic cancer cells. CD-BSB suppressed phosphorylation of focal adhesion kinase (FAK). In addition, pFAK 397 was inhibited by CD-BSB in a concentration-dependent manner in cancer cells. In the subcutaneous xenograft models, the tumor volume in the CD-BSB groups was lower than Control groups. Ki67-positive cells in CD-BSB treated group were lower than the GEM-treated groups.

Conclusion: We clarified the efficiency of CD-BSB in xenograft tumor using intravenous administration. α-Bisabolol suppresses phosphorylation of FAK 397 and impairs cytoskeletal polymerization in a pancreatic cancer cell line. Further investigations are required to reveal the precise mechanisms of the antitumor effects of solubilized α-bisabolol to facilitate its clinical application. Our data indicate that solubilized α-bisabolol has therapeutic potential and could improve the prognosis of cancer patients.

Keywords: FAK; antitumor effects; apoptosis; cyclodextrin; pancreatic cancer; α-Bisabolol.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cyclodextrins* / pharmacology
  • Disease Models, Animal
  • Focal Adhesion Protein-Tyrosine Kinases / drug effects
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Humans
  • Monocyclic Sesquiterpenes* / pharmacology
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / metabolism
  • Phosphorylation

Substances

  • bisabolol
  • Cyclodextrins
  • Focal Adhesion Protein-Tyrosine Kinases
  • Monocyclic Sesquiterpenes