Insight into the apoptosis-inducing action of alpha-bisabolol towards malignant tumor cells: involvement of lipid rafts and Bid.
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.
Darra
Elena
E
Dipartimento di Scienze Morfologico-Biomediche, Università di Verona, Strada Le Grazie, 8, 37134 Verona, Italy.
Abdel-Azeim
Safwat
S
Manara
Anna
A
Shoji
Kazuo
K
Maréchal
Jean-Didier
JD
Mariotto
Sofia
S
Cavalieri
Elisabetta
E
Perbellini
Luigi
L
Pizza
Cosimo
C
Perahia
David
D
Crimi
Massimo
M
Suzuki
Hisanori
H
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
D051023:BH3 Interacting Domain Death Agonist Protein; D000081222:Monocyclic Sesquiterpenes; D011994:Recombinant Proteins; D012717:Sesquiterpenes; C004497:bisabolol; D053148:Caspase 3