MIN-HSIUNG PANLin, J.-H.J.-H.LinLin-Shiau, S.-Y.S.-Y.Lin-ShiauLin, J.-K.J.-K.Lin2018-09-102018-09-101999http://www.scopus.com/inward/record.url?eid=2-s2.0-0032748332&partnerID=MN8TOARShttp://scholars.lib.ntu.edu.tw/handle/123456789/347566Penta-O-galloyl-β-D-glucose is structurally related to (-)- epigallocatechin gallate and is isolated from hydrolyzed tannin. Penta-O- galloyl-β-D-glucose can inhibit tumor promotion by teleocidin. We investigated the effects of penta-O-galloyl-β-D-glucose and various tea polyphenols on cell viability in human leukemia HL-60 cells. In this study, we demonstrated that penta-O-galloyl-β-D-glucose was able to induce apoptosis in a concentration- and time-dependent manner; however, other polyphenols were less effective. We further investigated the molecular mechanisms of penta-O-galloyl-β-D-glucose-induced apoptosis. Treatment with penta-O-galloyl-β-D-glucose caused induction of caspase-3/CPP32 activity in dose- and time-dependent manner, but not caspase-1 activity, and induced the degradation of poly-(ADP-ribose) polymerase. Pretreatment with acetyl-Asp- Glu-Val-Asp-aldehyde (Ac-DEVD-CHO) and Z-Val-Ala-Asp-fluoromethylketone (Z- VAD-FMK) inhibited penta-O-galloyl-β-D-glucose-induced DNA fragmentation. Furthermore, treatment with penta-O-galloyl-β-D-glucose (50 μM) caused a rapid loss of mitochondrial transmembrane potential, release of mitochondrial cytochrome c into cytosol, and subsequent induction of procaspase-9 processing. Our results indicate that penta-O-galloyl-β-D-glucose allows caspase-activated deoxyribonuclease to enter the nucleus and degrade chromosomal DNA, and induces DFF-45 (DNA fragmentation factor) degradation. These results lead to a working hypothesis that penta-O-galloyl-β-D-glucose- induced apoptosis is triggered by the release of cytochrome c into the cytosol, procaspase-9 processing, activation of caspase-3, degradation of poly-(ADP-ribose) polymerase, and DNA fragmentation caused by the caspase- activated deoxyribonuclease through the digestion of DFF-45. The induction of apoptosis by penta-O-galloyl-β-D-glucose may provide a pivotal mechanism for its cancer chemopreventive action.Apoptosis; Caspase- 3; Caspase-9; Caspase-activated deoxyribonuclease; Cytochrome c; DNA fragmentation factor; Penta-O-galloyl-β-D-glucose; Poly-(ADP-ribose) polymerase[SDGs]SDG3caspase 3; DNA fragment; glucose pentagallate; interleukin 1beta converting enzyme; apoptosis; article; cancer prevention; cell viability; concentration response; DNA degradation; drug activity; enzyme activation; human; human cell; leukemia; priority journal; Acridine Orange; Apoptosis; Blotting, Western; Caspase 3; Caspases; Cell Division; DNA Fragmentation; DNA, Neoplasm; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Enzyme Activation; Enzyme Inhibitors; Flow Cytometry; Fluorescent Dyes; HL-60 Cells; Humans; Hydrolyzable Tannins; Membrane Potentials; Mitochondria; Na(+)-K(+)-Exchanging ATPase; Subcellular Fractions; Tanninsjournal article10.1016/S0014-2999(99)00549-X