title: Didodecyldimethylammonium bromide (DDAB) induces caspase-mediated apoptosis in human leukemia HL-60 cells.
abstract: Didodecyldimethylammonium bromide (DDAB) is widely used for an efficient delivery system into mammalian cells. However, the biological activities of DDAB nanoparticles in mammalian cells are insufficiently understood. The purpose of this study was to establish a critical role of DDAB in cellular response. Here, we demonstrate that DDAB is a potent inducer of cell death in a wide range of tumor cell lines, wherein leukemia cells (HL-60 and U937) and neuroblastoma cells (Neuro2a) were more sensitive to DDAB than carcinoma cells such as HepG2 and Caco-2 cells. Moreover, in HL-60 cells, treatment with DDAB led to increased numbers of apoptotic cells with fragmented DNA (99.6%) and high levels of caspase-3 activation in comparison to that with actinomycin D. Cotreatment with a caspase-8 inhibitor (Z-IETD-FMK) or a polyethylene glycol (Mr 2000) (PEG 2000) effectively prevented the activation of caspase-3 induced by DDAB. These results suggest that DDAB can trigger caspase-3-mediated apoptosis through the extrinsic caspase-8 pathway and cytotoxic pore formation in cell membrane. Therefore, the present findings provide new insight into the biological activity of DDAB to induce caspase-mediated apoptosis.
authors.affiliation: Department of Biological Chemistry, Biotechnology and Food Research Institute, Fukuoka Industrial Technology Center, Kurume, Fukuoka 8390861, Japan. kkusumoto@fitc.pref.fukuoka.jp
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Kusumoto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ishikawa
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism*; D061945:Caspase Inhibitors; D018929:Cell Culture Techniques; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D008027:Light; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000494:pharmacology*; D012542:Scattering, Radiation; D013501:Surface-Active Agents / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D061945:Caspase Inhibitors; D004337:Drug Carriers; D004791:Enzyme Inhibitors; D000644:Quaternary Ammonium Compounds; D013501:Surface-Active Agents; C046112:didodecyldimethylammonium; D053148:Caspase 3