Morin inhibits the growth of human leukemia HL-60 cells via cell cycle arrest and induction of apoptosis through mitochondria dependent pathway.
The effects of morin (3,5,7,20,40-pentahydroxyflavone) on human leukemia HL-60 cells in vitro were investigated and the molecular mechanisms of morin-induced G2/M arrest and apoptosis in HL-60 cells were examined. Morin induced morphological changes and decreased the percentage of viable cells via induction of G2/M-phase arrest and apoptosis. Morin-induced G2/M-phase arrest was accompanied by the promotion of p21 and Wee1, and decreased levels of Cdc25c and cyclins A and B1 complex. Morin-induced apoptosis in HL-60 cells was also confirmed by flow cytometric assay, DNA gel electrophoresis for DNA fragmentation and DAPI staining. Morin induced apoptosis in time- and dose-dependent manners. Morin-induced apoptosis was associated with elevated intracellular reactive oxygen species (ROS) increased and Ca2+ production; decreased the levels of mitochondria membrane potential (deltapsi(m)) and increased caspase-3 activation. Collectively, these results suggest that the morin-induced apoptosis in HL-60 cells may result from the activation of caspase-3 and intracellular Ca2+ release, as well as the mitochondria membrane potential pathway.
Kuo
Hsiu-Maan
HM
Department of Parasitology, China Medical University, Taichung, Taiwan, ROC.
Chang
Li-Sheng
LS
Lin
Ya-Ling
YL
Lu
Hsu-Feng
HF
Yang
Jai-Sing
JS
Lee
Jau-Hong
JH
Chung
Jing-Gung
JG
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D064447:Checkpoint Kinase 2; D019925:Cyclin A / Q000096:biosynthesis; D019926:Cyclin B / Q000096:biosynthesis; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D005456:Fluorescent Dyes; D016195:G2 Phase / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007211:Indoles; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009687:Nuclear Proteins / Q000096:biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D051020:bcl-X Protein / Q000096:biosynthesis; D020687:cdc25 Phosphatases / Q000096:biosynthesis; D047309:Flavones
D000975:Antioxidants; D002118:Calcium; D020169:Caspases; D018797:Cell Cycle Proteins; D064447:Checkpoint Kinase 2; D019925:Cyclin A; D019926:Cyclin B; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005419:Flavonoids; D005456:Fluorescent Dyes; D007211:Indoles; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D020687:cdc25 Phosphatases; C494826:BAX protein, human; C494811:BCL2L1 protein, human; C534699:CCNB1 protein, human; C493956:CDKN1A protein, human; C007293:DAPI; C008548:morin; D047309:Flavones; C499349:WEE1 protein, human; C578634:CHEK2 protein, human; C517009:CDC25C protein, human