INSIGHT INTO THE APOPTOSIS-INDUCING ACTION OF alfa-BISABOLOL TOWARDS MALIGNANT TUMOUR CELLS: INVOLVEMENT OF LIPID RAFTS AND BID

Elena Darra, Kazuo Shoji, Sofia Mariotto, Elisabetta Cavalieri,*Luigi Perbellini, **Massimo Crimi, Hisanori Suzuki Dipartimento di Scienze Morfologico-Biomediche, Università di Verona, *Dipartimento di Medicina e Sanità Pubblica, Università di Verona, **Dipartimento Scientifico Tecnologico, Università di Verona, 37134 Verona, Italy

In the precedent report we showed that a-bisabolol, the sesquiterpen present widely in the plant kingdom, exerts a rapid and efficient apoptosis-inducing action selectively towards human and mice malignant glioblastoma cell lines through mitochondrial damage. The present study extends these data demonstrating its apoptosis-inducing action towards highly malignant human pancreatic carcinoma cell lines without affecting human fibroblast viability. The present study further shows the preferential incorporation of alfa-bisabolol to transformed cells through lipid rafts on plasma membranes and, thereafter, direct interaction between alfa-bisabolol and Bid protein, one of pro-apoptotic Bcl2 family proteins, analysed either by Surface Plasmon Resonance method or by intrinsic fluorescence measurement. Notions that lipids 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 alfa-bisabolol action may include its capacity to interact with Bid protein.