title: Induction of apoptosis by 3,4'-dimethoxy-5-hydroxystilbene in human promyeloid leukemic HL-60 cells.
abstract: 3, 4'-Dimethoxy-5-hydroxystilbene (DMHS) is a hydroxystilbene compound obtained by methylation and acid hydrolysis of piceid (resveratrol-3-O-glucoside) from Polygonum cuspidatum. Herein, we report that DMHS induces programmed cell death or apoptosis in human promyelocytic leukemic HL-60 cells. We found that treatment of HL-60 cells with DMHS suppressed the cell growth in a concentration-dependent manner with an IC50 value of 25 microM. DMHS increased internucleosomal DNA fragmentation in a time-dependent manner. The cell death by DMHS was partially prevented by the caspase inhibitor, zVAD-fmk. DMHS caused activation of caspases such as caspase-3, -8, and -9. Immunoblot experiments revealed that DMHS-induced apoptosis was associated with the induction of Bax expression. The release of cytochrome c from mitochondria into the cytosol was increased in response to DMHS. Taken together, our present results indicated that DMHS leads to apoptotic cell death in HL-60 cells through increased Bax expression and release of cytochrome c into cytosol and may be considered as a good candidate for a cancer chemopreventive agent in humans.
authors.affiliation: College of Pharmacy, Chungang University, Seoul, Korea.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Shi Yong
authors.initials: SY
authors.lastname: Ryu
authors.forename: Han Bok
authors.initials: HB
authors.lastname: Kim
authors.forename: Mie Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Chun
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003574:Cytochrome c Group / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D018922:HL-60 Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D028502:Polygonum; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D015398:Signal Transduction; D013267:Stilbenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein
chemical_list: C455062:3,4'-dimethoxy-5-hydroxystilbene; D000590:Amino Acid Chloromethyl Ketones; D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D061945:Caspase Inhibitors; D003574:Cytochrome c Group; D004365:Drugs, Chinese Herbal; D005960:Glucosides; D010936:Plant Extracts; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013267:Stilbenes; D051028:bcl-2-Associated X Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; C058229:polydatin