Induction of apoptosis by 3,4'-dimethoxy-5-hydroxystilbene in human promyeloid leukemic HL-60 cells.
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.
Lee
Sung Hee
SH
College of Pharmacy, Chungang University, Seoul, Korea.
Ryu
Shi Yong
SY
Kim
Han Bok
HB
Kim
Mie Young
MY
Chun
Young Jin
YJ
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
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