title: Lupiwighteone induces cell cycle arrest and apoptosis and activates the Nrf2/ARE pathway in human neuroblastoma cells.
abstract: Lupiwighteone (Lup) is a kind of natural isoflavone, but its pharmacological effect and active mechanism are rarely reported. This study aimed to investigate the anticancer and cancer preventive effects of Lup on human neuroblastoma (SH-SY5Y) cells. We found that Lup could inhibit SH-SY5Y cells growth in a concentration- and time-dependent manner. Further studies suggested that Lup could induce G2/M phase arrest associated with an evident decrease in cyclin B1/D1 and cyclin dependent kinase (CDK) 1/2/4/6 protein expressions. Moreover, Lup could regulate the changes of mitochondrial membrane potential and increase intracellular reactive oxygen species (ROS) production. After the cells were treated with Lup, topical morphological characteristics were observed; apoptosis-related protein expressions, such as Bax, cytochrome c, cleaved caspase-9, cleaved caspase-3 and cleaved PARP-1 were increased; and protein expressions, such as Bcl-2, procaspase-9, PARP-1 and P-Akt were decreased. These changes were observed simultaneously. In addition, Nrf2 transcription factor activation was detected by an ARE-GFP reporter assay. Nrf2 nuclear localization was then investigated using a fluorescence microscope. Furthermore, Nrf2 and Keap1 protein levels were determined by western blot. Our results may provide a scientific basis for the application of the anticancer and cancer preventive effects of Lup on SH-SY5Y cells.
authors: School of Pharmaceutical Engineering & Life Science, Changzhou University, 1, Gehu Road, Changzhou, Jiangsu 213164, PR China. Electronic address: renjie2006@163.com.
authors: Jie
authors: J
authors: Ren
authors: School of Pharmaceutical Engineering & Life Science, Changzhou University, 1, Gehu Road, Changzhou, Jiangsu 213164, PR China.
authors: Jie
authors: J
authors: Yang
authors: School of Pharmaceutical Engineering & Life Science, Changzhou University, 1, Gehu Road, Changzhou, Jiangsu 213164, PR China.
authors: Yuanyuan
authors: Y
authors: Xu
authors: School of Pharmaceutical Engineering & Life Science, Changzhou University, 1, Gehu Road, Changzhou, Jiangsu 213164, PR China.
authors: Qianhui
authors: Q
authors: Huang
authors: School of Pharmaceutical Engineering & Life Science, Changzhou University, 1, Gehu Road, Changzhou, Jiangsu 213164, PR China.
authors: Meng
authors: M
authors: Yang
authors: School of Pharmaceutical Engineering & Life Science, Changzhou University, 1, Gehu Road, Changzhou, Jiangsu 213164, PR China. Electronic address: hukun1979@163.com.
authors: Kun
authors: K
authors: Hu
mesh_terms: D061745:Antioxidant Response Elements / Q000235:genetics*; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology*; D021381:Protein Transport / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018797:Cell Cycle Proteins; D007529:Isoflavones; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; C000602100:lupiwighteone
keywords: Apoptosis; Lupiwighteone; Nrf2