α-bisabolol is an effective proapoptotic agent against bcr-abl+ cells in synergism with imatinib and nilotinibα-bisabolol是一种有效的proapoptotic代理对bcr - abl +细胞与伊马替尼和nilotinib合作.pdfVIP

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α-bisabolol is an effective proapoptotic agent against bcr-abl+ cells in synergism with imatinib and nilotinibα-bisabolol是一种有效的proapoptotic代理对bcr - abl +细胞与伊马替尼和nilotinib合作.pdf

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α-bisabololisaneffectiveproapoptoticagentagainstbcr-ablcellsinsynergismwithimatinibandnilotinibα-bisabolol是一种有效的proapoptotic代理对bcr-abl细胞与伊马替尼和nilotinib合作

a-bisabolol Is an Effective Proapoptotic Agent against BCR-ABL+ Cells in Synergism with Imatinib and Nilotinib 1 1 1 2 Massimiliano Bonifacio , Antonella Rigo , Emanuele Guardalben , Christian Bergamini , 3 2 1 3{ 1 Elisabetta Cavalieri , Romana Fato , Giovanni Pizzolo , Hisanori Suzuki , Fabrizio Vinante * 1 Department of Medicine, Section of Hematology, University of Verona, Verona, Italy, 2 Department of Biochemistry ‘‘G. Moruzzi’’, University of Bologna, Bologna, Italy, 3 Department of Life and Reproduction Sciences, Section of Biochemistry, University of Verona, Verona, Italy Abstract We showed that a-bisabolol is active against primary acute leukemia cells, including BCR-ABL+ acute lymphoblastic leukemias (ALL). Here we studied the activity of a-bisabolol against BCR-ABL+ cells using 3 cell lines (K562, LAMA-84, CML- T1) and 10 primary BCR-ABL+ ALL samples. We found that: (a) a-bisabolol was effective in reducing BCR-ABL+ cell viabilty at concentrations ranging from 53 to 73 mM; (b) a-bisabolol concentrations in BCR-ABL+ cellular compartments were 4- to 12- fold higher than in normal cells, thus indicating a preferential intake in neoplastic cells; (c) a-bisabolol displayed a slight to strong synergism with the Tyrosine Kinase Inhibitors (TKI) imatinib and nilotinib: the combination of a-bisabolol+imatinib allowed a dose reduction of each compound up to 7.2 and 9.4-fold respectively, while the combination of a- bisabolol+nilotinib up to 6.7 and 5-fold respectively; (d) a-bisabolol-induced apoptosis was ass