title: Insight into the apoptosis-inducing action of alpha-bisabolol towards malignant tumor cells: involvement of lipid rafts and Bid.
abstract: 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.
authors.affiliation: Dipartimento di Scienze Morfologico-Biomediche, Università di Verona, Strada Le Grazie, 8, 37134 Verona, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Darra
authors.forename: Safwat
authors.initials: S
authors.lastname: Abdel-Azeim
authors.forename: Anna
authors.initials: A
authors.lastname: Manara
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shoji
authors.forename: Jean-Didier
authors.initials: JD
authors.lastname: Maréchal
authors.forename: Sofia
authors.initials: S
authors.lastname: Mariotto
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cavalieri
authors.forename: Luigi
authors.initials: L
authors.lastname: Perbellini
authors.forename: Cosimo
authors.initials: C
authors.lastname: Pizza
authors.forename: David
authors.initials: D
authors.lastname: Perahia
authors.forename: Massimo
authors.initials: M
authors.lastname: Crimi
authors.forename: Hisanori
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000032:analysis / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D000081222:Monocyclic Sesquiterpenes; D010190:Pancreatic Neoplasms / Q000473:pathology; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*; D020349:Surface Plasmon Resonance; D013997:Time Factors
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D000081222:Monocyclic Sesquiterpenes; D011994:Recombinant Proteins; D012717:Sesquiterpenes; C004497:bisabolol; D053148:Caspase 3