title: Isoliquiritigenin-induced effects on Nrf2 mediated antioxidant defence in the HL-60 cell monocytic differentiation.
abstract: To evaluate the role of redox homeostasis in differentiation in human promyelocytic leukemia cells (HL-60) induced by isoliquiritigenin (ISL) through modulation of the nuclear erythroid-related factor 2/antioxidant responsive element (Nrf2/ARE) pathway. Morphological changes, cell surface markers CD11b/CD14, and nitroblue tetrazolium (NBT)-reducing ability were used to determine the differentiation of HL-60, and 2,7-dichlorofluorescein was used to detect the level of intracellular reactive oxygen species (ROS). Thiobarbituric acid test was utilised to determine the levels of malondialdehyde production in ISL-treated HL-60. The study determines and presents the redox state of the ratio of reduced/oxidised glutathione as a consequence of progression from differentiation in HL-60. Expression levels of the Nrf2/ARE downstream target genes were determined by quantitative polymerase chain reaction. Nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) inhibitors, apocynin (APO), and diphenyleneiodonium (DPI) were used for the preliminary study to determine the potential downstream targets regulated by NADPH oxidase in ISL-induced HL-60 differentiation. The data showed a strong dose-response relationship between ISL exposure and the characteristics of HL-60 differentiation, namely, morphology changes, NBT reductive activities, and expression levels of surface antigens CD11b/CD14. Intercellular redox homeostasis changes toward oxidation during drug exposure are necessary to support ISL-induced differentiation. The unique expression levels of the Nrf2/ARE downstream target genes in the differentiation of HL-60 recorded a statistically significant and dose-dependent increase (P < 0.05), which were suppressed by NADPH oxidase inhibitor, APO, and DPI. ISL as a differentiation-inducing agent with mechanisms involved in the Nrf2/ARE pathway to modulate intercellular redox homeostasis, and thus, facilitate differentiation.
authors.affiliation: Life Science School, Yantai University, Yantai, 264005, China; Key Laboratory of Xinjiang Endemic Phytomedicine Resources of Ministry of Education, School of Pharmacy, Shihezi University, Shihezi, 832002, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Chen
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Xuan
authors.initials: X
authors.lastname: Yuan
authors.forename: Ying
authors.initials: Y
authors.lastname: Yao
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Xiling
authors.initials: X
authors.lastname: Sun
authors.forename: Quisheng
authors.initials: Q
authors.lastname: Zheng
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D047188:Chalcones / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000494:pharmacology; D018922:HL-60 Cells; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D009861:Onium Compounds / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D020218:Response Elements / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D000098:Acetophenones; D000975:Antioxidants; D047188:Chalcones; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D009861:Onium Compounds; C007517:diphenyleneiodonium; C056165:acetovanillone; C040920:isoliquiritigenin; D019255:NADPH Oxidases; D005978:Glutathione
keywords: Nrf2; differentiation; glutathione; isoliquiritigenin; redox signalling