Cyclodextrin Conjugated alpha-Bisabolol Suppresses FAK Phosphorylation and Induces Apoptosis in Pancreatic Cancer
Anticancer research(2023)
摘要
Background/Aim: alpha-Bisabolol is an essential oil component extracted from plants, such as chamomile. We have previously reported that alpha-bisabolol suppressed proliferation, invasion, and motility of pancreas cancer. Cyclodextrin improved the solubility of alpha-bisabolol, therefore it enabled to administer intravenously. The aim of this study was to clarify the effect of cyclodextrin conjugated alpha-bisabolol (CD-BSB) and the signals pathways associated with alpha-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. alpha-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 alpha-bisabolol to facilitate its clinical application. Our data indicate that solubilized alpha-bisabolol has therapeutic potential and could improve the prognosis of cancer patients.
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关键词
?-Bisabolol,cyclodextrin,FAK,pancreatic cancer,antitumor effects,apoptosis
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