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

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 αbisabolol (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 GEMtreated 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 αbisabolol to facilitate its clinical application. Our data indicate that solubilized α-bisabolol has therapeutic potential and could improve the prognosis of cancer patients.

Chitosan and Cyclodextrins—Versatile Materials Used to Create Drug Delivery Systems for Gastrointestinal Cancers

“…Kano et al [ 130 ] have recently synthesized cyclodextrin-conjugated α-bisabolol and tested it against pancreatic cancer cells. The authors reported significant modifications of cytomorphology, apoptosis induction, and the suppression of phosphorylation of focal adhesion kinase.…”

“…One study also reports using an oral chitosan-based formulation that ensured desirable stability in a simulated gastrointestinal environment, with slow cumulative drug release displayed in simulated gastrointestinal fluids without enzymes and in body fluid [ 113 ]. As for pancreatic cancer, cyclodextrin-based formulations were reported for intravenous injection [ 128 , 130 ], oral delivery [ 133 ] (demonstrated by in vivo studies to facilitate absorption and avoid pre-systemic metabolism, increasing the bioavailability of the carried drug), and potential suitability for both oral and parenteral administration [ 131 ] (only tested in vitro). Differently, among the chitosan-based formulations designed for a specific type of administration for fighting pancreatic cancer, one was engineered for intravenous delivery via folate receptor targeting [ 135 ], and two were developed for oral administration based on the intrinsic properties of this natural polymer [ 136 , 138 ].…”