title: Ethanol extract of Hedyotis diffusa willd upregulates G0/G1 phase arrest and induces apoptosis in human leukemia cells by modulating caspase cascade signaling and altering associated genes expression was assayed by cDNA microarray.
abstract: The authors' previous study has shown that water extract of Hedyotis diffusa Willd (HDW) promoted immune response and exhibited anti-leukemic activity in BALB/c leukemic mice in vivo. In this study, the anti-proliferation effects of ethanol extract of H. diffusa Willd (EEHDW) on lung cancer cell lines (A549, H1355, and LLC), leukemia cell lines (HL-60, WEHI-3), and a mouse melanoma cell line (B16F10) in vitro were investigated. The results demonstrated that EEHDW suppressed the cell proliferation of A549, H1355, HL-60, WEHI-3, and B16F10 cells as well as reduced cell viability in a concentration-dependent manner. We found that EEHDW inhibited the cell proliferation of HL-60 cells in concentration-dependent manner. In addition, EEHDW triggered an arrest of HL-60 cells at G0/G1 phase and sub-G1 population (apoptotic cells). EEHDW provoked DNA condensation and DNA damage in HL-60 cells. The activities of caspase-3, caspase-8, and caspase-9 were elevated in EEHDW-treated HL-60 cells. DNA microarray to investigate and display the gene levels related to cell growth, signal transduction, apoptosis, cell adhesion, cell cycle, DNA damage and repair, transcription and translation was also used. These findings suggest that EEHDW may be a potential herbal medicine and therapeutic agent for the treatment of leukemia.
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Yu-Jui
authors.initials: YJ
authors.lastname: Kuo
authors.affiliation: Department of Pharmacology, China Medical University, Taichung, Taiwan.
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.affiliation: Department of Life Sciences, National Chung Hsing University, 250, Kuo-Kuang Road, Taichung, 402, Taiwan.
authors.forename: Chi-Cheng
authors.initials: CC
authors.lastname: Lu
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Su-Yin
authors.initials: SY
authors.lastname: Chiang
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Jaung-Geng
authors.initials: JG
authors.lastname: Lin
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.|Department of Biotechnology, Asia University, Taichung 413, Taiwan, People's Republic of China.
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D000431:Ethanol / Q000737:chemistry; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D018922:HL-60 Cells; D032064:Hedyotis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000473:pathology; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010936:Plant Extracts / Q000737:chemistry / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; D010936:Plant Extracts; D000431:Ethanol; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases
keywords: G0/G1 phase arrest; Hedyotis diffusa Willd; apoptosis; human leukemia cells; cDNA Microarray