title: Sophoraflavanone G Induces Apoptosis in Human Leukemia Cells and Blocks MAPK Activation.
abstract: Sophoraflavanone G (SG) was isolated from Sophora flavescens. Previously, we have found that SG is able to suppress the inflammatory response in lipopolysaccharide-stimulated RAW 264.7 macrophages. This study aimed to evaluate the effects of SG on apoptosis, and explore its molecular mechanism in human leukemia HL-60 cells. HL-60 cells were treated with various concentrations of SG (3-30 [Formula: see text]M). The viability of the HL-60 cells was assessed using the MTT method, and the nuclear condensation indicative of apoptosis was observed by DAPI fluorescence staining. In addition, apoptotic signal proteins were examined using Western blotting. The results showed that apoptosis, including DNA fragmentation and nuclear condensation, increased significantly in SG-treated HL-60 cells. SG activated caspase-3 and caspase-9, and downregulated Bcl-2 and Bcl-xL. SG also upregulated Bax and released cytochrome c from the mitochondria into the cytoplasm, enabling apoptosis via the mitochondrially-mediated "intrinsic" pathway. Additionally, SG was able to cleave poly (ADP-ribose) polymerase 1 and activate mitogen-activated protein kinase (MAPK) pathways. These results suggest that SG might increase the effect of apoptosis on HL-60 cells through caspase-3 activation, mitochondrial-mediated pathways, and the MAPK pathway.
authors.affiliation: * Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Guishan District, Taoyuan City, Taiwan.
authors.forename: Zih-Ying
authors.initials: ZY
authors.lastname: Li
authors.affiliation: † Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Guishan District, Taoyuan City, Taiwan.|‡ Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Guishan District, Taoyuan City, Taiwan.
authors.forename: Wen-Chung
authors.initials: WC
authors.lastname: Huang
authors.affiliation: * Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Guishan District, Taoyuan City, Taiwan.
authors.forename: Rong-Syuan
authors.initials: RS
authors.lastname: Tu
authors.affiliation: * Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Guishan District, Taoyuan City, Taiwan.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Gu
authors.affiliation: § Department of Cosmetic Sciences, Chang Gung University of Science and Technology, Guishan District, Taoyuan City, Taiwan.
authors.forename: Chwan-Fwu
authors.initials: CF
authors.lastname: Lin
authors.affiliation: ‡ Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Guishan District, Taoyuan City, Taiwan.|¶ Department of Nursing, Chang Gung University of Science and Technology, Guishan District, Taoyuan City, Taiwan.
authors.forename: Chian-Jiun
authors.initials: CJ
authors.lastname: Liou
mesh_terms: D000893:Anti-Inflammatory Agents; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D044950:Flavanones / Q000302:isolation & purification / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000201:enzymology* / Q000473:pathology*; D008928:Mitochondria / Q000201:enzymology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics*; D029909:Sophora / Q000737:chemistry; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D044950:Flavanones; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D045304:Cytochromes c; C064849:vexibinol; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053453:Caspase 9
keywords: Apoptosis; Bax; Caspase-3; PARP-1; Sophoraflavanone G