bisabolol and Pancreatic-Neoplasms

Alpha-bisabolol is a plant-derived sesquiterpene alcohol recently associated with a supposed anti-cancer action due to its ability to induce BID-related apoptosis. The molecule, which enters the cell through lipid rafts, may also interact with kisspeptin receptor 1, which has recently been associated with tumor mobility and invasiveness. This evidence suggests the possibility that α-bisabolol might act on the epithelial-mesenchymal transition mechanism, closely associated with the desmoplastic reaction of adipose tissue surrounding a pancreatic ductal adenocarcinoma. This review addresses the issue on the basis of the most recent reported literature in the field.

Topics: Adipocytes; Carcinoma, Pancreatic Ductal; Epithelial-Mesenchymal Transition; Humans; Monocyclic Sesquiterpenes; Pancreatic Neoplasms; Sesquiterpenes; Tumor Microenvironment

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.. 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).. 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.. 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.

Topics: Animals; Apoptosis; Cyclodextrins; Disease Models, Animal; Focal Adhesion Protein-Tyrosine Kinases; Humans; Monocyclic Sesquiterpenes; Pancreatic Neoplasms; Phosphorylation

Pancreatic cancer is highly malignant, characterized by aggressive proliferation, invasion, and metastasis. α-Bisabolol is an oily sesquiterpene alcohol derived from a variety of plants. We previously demonstrated that α-bisabolol is a potential therapeutic agent for pancreatic cancer. The aim of this study was to develop α-bisabolol derivatives which are more potent than the parent compound and may be clinically useful against pancreatic cancer. First, 22 derivatives of α-bisabolol were designed and synthesized. α-Bisabolol derivatives

Topics: Animals; Antigens, Tumor-Associated, Carbohydrate; Antineoplastic Agents; Apoptosis; Blotting, Western; Carcinoembryonic Antigen; Cell Line, Tumor; Cell Proliferation; Cell Survival; Humans; Male; Mice, Inbred BALB C; Mice, Nude; Molecular Structure; Monocyclic Sesquiterpenes; Pancreatic Neoplasms; Proto-Oncogene Proteins c-akt; Sesquiterpenes; Xenograft Model Antitumor Assays

α-Bisabolol is a plant-derived, oily sesquiterpene alcohol that induces apoptosis of various cancer cells. We previously reported the antiproliferative effects of α-bisabolol on pancreatic cancer cell lines using in vitro and in vivo experiments. However, the effects of α-bisabolol on tumor invasiveness and motility are still unknown. In this study, demonstrated that α-bisabolol suppressed the invasiveness and motility of a pancreatic cancer cell line. Although Early growth response 1 (EGR1) was involved in antiproliferative effects of α-bisabolol, it had no relationship with the inhibitory effect of α-bisabolol on cellular invasiveness and motility. Polymerase chain reaction analysis revealed that α-bisabolol induced Kisspeptin 1 receptor (KISS1R) in pancreatic cancer cell lines. The inhibition of KISS1R weakened the inhibitory effect of α-bisabolol on invasiveness of pancreatic cancer cells. The results also implied that the inhibitory effects of α-bisabolol on tumor invasiveness and motility are at least partly associated with the activation of KISS1R. However, there is a possibility that other molecular mechanisms of α-bisabolol regulate invasiveness and motility in pancreatic cancer cells. Further investigations are necessary to clarify the precise mechanisms of α-bisabolol activity for clinical application as a novel treatment for pancreatic cancer.

Topics: Apoptosis; Blotting, Western; Cell Movement; Cell Proliferation; Early Growth Response Protein 1; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Monocyclic Sesquiterpenes; Neoplasm Invasiveness; Pancreatic Neoplasms; Real-Time Polymerase Chain Reaction; Receptors, G-Protein-Coupled; Receptors, Kisspeptin-1; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Small Interfering; Sesquiterpenes; Tumor Cells, Cultured

In the present study, we investigated whether α-bisabolol, a sesquiterpene alcohol present in essential oils derived from a variety of plants, has antitumor effects against pancreatic cancer. α-Bisabolol induced a decrease in cell proliferation and viability in pancreatic cancer cell lines (KLM1, KP4, Panc1, MIA Paca2), but not in pancreatic epithelial cells (ACBRI515). α-Bisabolol treatment induced apoptosis and suppressed Akt activation in pancreatic cancer cell lines. Furthermore, α-bisabolol treatment induced the overexpression of early growth response-1 (EGR1), whereas EGR1 siRNA decreased the α-bisabolol-induced cell death of KLM1 cells. Tumor growth in both subcutaneous and peritoneal xenograft nude mouse models was significantly inhibited by intragastric administration of 1000 mg/kg of α-bisabolol, once a week for three weeks. The results indicate that α-bisabolol could be a novel therapeutic option for the treatment of pancreatic cancer.

Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Early Growth Response Protein 1; Epithelial Cells; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Monocyclic Sesquiterpenes; Pancreatic Neoplasms; Plant Oils; Proto-Oncogene Proteins c-akt; RNA Interference; RNA, Small Interfering; Sesquiterpenes; Xenograft Model Antitumor Assays

In a precedent report we showed that alpha-bisabolol, a sesquiterpene present widely in the plant kingdom, exerts a rapid and efficient apoptosis-inducing action selectively towards human and murine malignant glioblastoma cell lines through mitochondrial damage. The present study extends these data demonstrating the apoptosis-inducing action of alpha-bisabolol towards highly malignant human pancreatic carcinoma cell lines without affecting human fibroblast viability. The present study further shows the preferential incorporation of alpha-bisabolol to transformed cells through lipid rafts on plasma membranes and, thereafter, direct interaction between alpha-bisabolol and Bid protein, one of pro-apoptotic Bcl-2 family proteins, analyzed either by Surface Plasmon Resonance method or by intrinsic fluorescence measurement. Notions that lipid rafts are rich in plasma membranes of transformed cells and that Bid, richly present in lipid rafts, is deeply involved in lipid transport make highly credible the hypothesis that the molecular mechanism of alpha-bisabolol action may include its capacity to interact with Bid protein.

Topics: Apoptosis; BH3 Interacting Domain Death Agonist Protein; Caspase 3; Cell Line, Tumor; Cell Survival; Humans; Membrane Microdomains; Membrane Potentials; Mitochondria; Models, Molecular; Molecular Structure; Monocyclic Sesquiterpenes; Pancreatic Neoplasms; Recombinant Proteins; Sesquiterpenes; Surface Plasmon Resonance; Time Factors