Modulation of the damaging actions of each or both drugs. AModulation of the damaging actions

Modulation of the damaging actions of each or both drugs. A
Modulation of the damaging actions of each or both drugs. A compound like a-bisabolol – and others [27] – could help to identify profitable new strategies for both mutated and nonmutated leukemias [9,28,29].JC-1 aggregatesJC-1 aggregatesCavalieri et al. Journal of Translational Medicine 2011, 9:45 12 ofOur biochemical data suggest a direct effect on mitochondrial integrity as a possible mechanism of a-bisabolol damage to leukemic cells. This behavior is supported by the observed oxygen consumption decrease in the presence of glutamate/malate and by the unaffected respiration rates in the presence of succinate/glycerol-3phosphate. Microscopy and flow cytometry data show that a-bisabolol disrupts m , which induces outer membrane permeabilization and leads to the apoptotic death of blasts. Our data not only implicate a-bisabolol for the first time in mitochondrial Lixisenatide chemical information impairment in human leukemic cells but also suggest that this goes through a peculiar model of cell death, i.e., the formation of a cellular population with intermediate D m which is a feature of apoptosis seen only in a few cell types and never described to date in leukemic blasts [30]. In all leukemia samples treated with a-bisabolol, BID was found to be expressed in a full-lenght form that was suitable for binding to a-bisabolol. We failed to demonstrate full-length BID translocation to the mitochondria in leukemic cells as a pro-apoptotic mechanism [19]. Nevertheless, BID might act as a carrier that conveys abisabolol to the mitochondrial membrane. Thus, according to our previous and present work, abisabolol enters cells via lipid rafts and directly involves mitochondrial permeability transition pore opening [20], which is responsible for the reduced glutamate/malatesupported oxygen consumption and leads to disruption of the mitochondrial membrane potential and programmed cell death. The reciprocal role of BID and abisabolol [3] remains elusive in leukemic cells.Authors’ contributions EC, AR, ACdP performed the research, analyzed data, and performed statistical analysis; MB, EG, CB, RF contributed analytical tools, performed selected experiments and analyzed data; GP contributed criticism; HS suggested the research, contributed ideas and critical scientific knowledge, analyzed and interpreted data; FV chose the clinical setting, designed and performed the research, analyzed and interpreted data, and wrote the paper; all authors checked the final version of the manuscript. Competing interests The authors declare that they have no competing interests. Received: 18 November 2010 Accepted: 21 April 2011 PubMed ID: Published: 21 April 2011 References 1. Cavalieri E, Mariotto S, Fabrizi C, De Prati AC, Gottardo R, Leone S, Berra LV, Lauro GM, Ciampa AR, Suzuki H: -bisabolol, a non-toxic natural compound, strongly induces apoptosis in glioma cells. Biochem Biophys Res Commun 2004, 315:589-594. 2. Costarelli L, Malavolta M, Giacconi R, Cipriano C, Gasparini N, Tesei S, Pierpaoli S, Orlando F, Suzuki H, Perbellini L, Piacenza F, Emanuelli M, Mocchegiani E: In vivo effect of alpha-bisabolol, a nontoxic sesquiterpene alcohol, on the induction of spontaneous mammary tumors in HER-2/neu transgenic mice. Oncol Res 2010, 18:409-418. 3. Darra E, Abdel-Azeim S, Manara A, Shoji K, Marechal JD, Mariotto S, Cavalieri E, Perbellini L, Pizza C, Perahia D, Crimi M, Suzuki H: Insight into the apoptosis-inducing action of -bisabolol towards malignant tumo.