title: Flow cytometric evaluation of synergistic pro-apoptotic effects of statins and clofibrates in IM-9 human lymphoblasts.
abstract: 1. In the present study, we evaluated fibrate-mediated potentiation of statin-induced apoptosis in IM-9 human lymphoblasts. 2. The pro-apoptotic effects of statin and fibrate were measured by flow cytometry with biotin-annexin V, followed by addition of avidin-fluorescein isothiocyanate and propidium iodide. Apoptosis was confirmed using karyopyknotic staining, as well as detection of DNA fragmentation and caspase 3 activation. 3. Incubation of IM-9 cells with both 0.1 micromol/L cerivastatin and 200 micromol/L clofibrate had a synergistic effect compared with 0.1 micromol/L cerivastatin alone or 200 micromol/L clofibrate alone. The magnitude of apoptosis induced by various combinations of statins and clofibrate were as follows: cerivastatin (0.1 micromol/L) + clofibrate (200 micromol/L) > atorvastatin (0.1 micromol/L) + clofibrate (200 micromol/L) > pravastatin (100 micromol/L) + clofibrate (200 micromol/L). Other fibrates (bezafibrate and clinofibrate) did not show any synergistic effect. Furthermore, karyopyknotic staining, caspase 3 activation and DNA fragmentation demonstrated synergistic pro-apoptotic effects of statin and fibrate. 4. The results of the present study suggest that simultaneous treatment with statins and clofibrate could provide improved therapeutic efficacy in leukaemia patients.
authors.affiliation: School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Tomiyama
authors.forename: Noriko
authors.initials: N
authors.lastname: Yasuda
authors.forename: Chihiro
authors.initials: C
authors.lastname: Iwano
authors.forename: Sumio
authors.initials: S
authors.lastname: Matzno
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsuyama
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000069059:Atorvastatin; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002994:Clofibrate / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D004357:Drug Synergism; D004789:Enzyme Activation; D005434:Flow Cytometry; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D017035:Pravastatin / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011725:Pyridines; D011758:Pyrroles; D000069059:Atorvastatin; C086276:cerivastatin; D053148:Caspase 3; D002994:Clofibrate; D017035:Pravastatin