1.The roles of c-Jun and CBP in the inhibitory effect of quercetin on prostate cancer cells.
Hui-qing YUAN ; Huai-fang GUO ; Mei-lan HE ; Feng KONG ; Xiao-Yan HU ; An-li JIANG ; Xia XU ; Jian-ye ZHANG ; Y F Young CHARLES
Acta Pharmaceutica Sinica 2006;41(9):819-824
AIMTo further uncover the possible mechanism of quercetin-mediated inhibitory effect on prostate cancer cells.
METHODSThe cell extracts treated with quercetin or without treatment were used for checking protein expression levels of c-Jun and cAMP response element binding protein (CREB)-binding protein (CBP) by Western blotting assay. Regulatory effects of c-Jun and CBP on the function of androgen receptor (AR) were examined by cotransfection experiment. Finally, a physical interaction of c-Jun and the AR was investigated by coimmunoprecipitation.
RESULTSQuercetin dramatically induced the protein expression of c-Jun which in turn inhibited the AR function. Meanwhile, quercetin had no detectable effect on CBP expression, and the results of transient transfection demonstrated that the ectopic CBP stimulated the transcriptional activity of AR, whereas CBP-mediated stimulation could be attenuated by quercetin. Furthermore, physical interaction of c-Jun and the AR was confirmed by coimmunoprecipitation result.
CONCLUSIONOverexpression of c-Jun induced by quercetin had inhibitory effect on the function of AR protein, and increased CBP expression did not reverse the inhibition by quercetin. Together, quercetin-mediated inhibition on the AR function might be not by competition with limited amount of CBP in the cell, but through a direct association of c-Jun and the AR.
Antineoplastic Agents, Phytogenic ; pharmacology ; CREB-Binding Protein ; genetics ; metabolism ; physiology ; Cell Line, Tumor ; Humans ; Immunoprecipitation ; Male ; Prostatic Neoplasms ; metabolism ; pathology ; Protein Binding ; drug effects ; Proto-Oncogene Proteins c-jun ; genetics ; metabolism ; physiology ; Quercetin ; pharmacology ; Receptors, Androgen ; genetics ; physiology ; Transfection
2.Hyperoside Induces Endogenous Antioxidant System to Alleviate Oxidative Stress.
Ji Young PARK ; Xia HAN ; Mei Jing PIAO ; Min Chang OH ; Pattage Madushan Dilhara Jayatissa FERNANDO ; Kyoung Ah KANG ; Yea Seong RYU ; Uhee JUNG ; In Gyu KIM ; Jin Won HYUN
Journal of Cancer Prevention 2016;21(1):41-47
BACKGROUND: Hyperoside, a flavonoid which is mainly found in Hypericum perforatum L., has many biological effects. One of the most important effects is to prevent the oxidative stress induced by reactive oxygen species. However, the molecular mechanisms underlying its effect are not fully understood. Oxidative stress is implicated in the occurrence of various physical diseases. A wide array of enzymatic antioxidant defense systems include NADH: quinone oxidoreductase 1, superoxide dismutase, and heme oxygenase-1 (HO-1). In the present study, the protective effects of hyperoside against hydrogen peroxide-induced oxidative stress in human lens epithelial cells, HLE-B3, were investigated in terms of HO-1 induction. METHODS: The protein and mRNA expressions of HO-1 were examined by Western blotting and reverse transcriptase-PCR assays, respectively. To evaluate the ability of hyperoside to activate nuclear factor erythroid 2-related factor 2 (Nrf2), Western blotting and electrophoretic mobility shift assay were performed with nuclear extracts prepared from HLE-B3 cells treated with hyperoside. The activation of extracellular signal-regulated kinase (ERK), the upstream kinase of Nrf2 signaling, was monitored by Western blot analysis. The protective effect of hyperoside in HLE-B3 cells against hydrogen peroxide was performed by MTT assay. RESULTS: Hyperoside increased both the mRNA and protein expression of HO-1 in a time- and dose-dependent manner. In addition, hyperoside elevated the level of of Nrf2 and its antioxidant response element-binding activity, which was modulated by upstream of ERK. Moreover, it activated ERK and restored cell viability which was decreased by hydrogen peroxide. CONCLUSIONS: Hyperoside is an effective compound to protect cells against oxidative stress via HO-1 induction.
Antioxidants
;
Blotting, Western
;
Cell Survival
;
Electrophoretic Mobility Shift Assay
;
Epithelial Cells
;
Heme Oxygenase-1
;
Humans
;
Hydrogen
;
Hydrogen Peroxide
;
Hypericum
;
NAD
;
Oxidative Stress*
;
Phosphotransferases
;
Reactive Oxygen Species
;
RNA, Messenger
;
Superoxide Dismutase
3.Isorhamnetin Protects Human Keratinocytes against Ultraviolet B-Induced Cell Damage.
Xia HAN ; Mei Jing PIAO ; Ki Cheon KIM ; Susara Ruwan Kumara MADDUMA HEWAGE ; Eun Sook YOO ; Young Sang KOH ; Hee Kyoung KANG ; Jennifer H SHIN ; Yeunsoo PARK ; Suk Jae YOO ; Sungwook CHAE ; Jin Won HYUN
Biomolecules & Therapeutics 2015;23(4):357-366
Isorhamnetin (3-methylquercetin) is a flavonoid derived from the fruits of certain medicinal plants. This study investigated the photoprotective properties of isorhamnetin against cell damage and apoptosis resulting from excessive ultraviolet (UV) B exposure in human HaCaT keratinocytes. Isorhamnetin eliminated UVB-induced intracellular reactive oxygen species (ROS) and attenuated the oxidative modification of DNA, lipids, and proteins in response to UVB radiation. Moreover, isorhamnetin repressed UVB-facilitated programmed cell death in the keratinocytes, as evidenced by a reduction in apoptotic body formation, and nuclear fragmentation. Additionally, isorhamnetin suppressed the ability of UVB light to trigger mitochondrial dysfunction. Taken together, these results indicate that isorhamnetin has the potential to protect human keratinocytes against UVB-induced cell damage and death.
Apoptosis
;
Cell Death
;
DNA
;
Fruit
;
Humans
;
Keratinocytes*
;
Plants, Medicinal
;
Reactive Oxygen Species
4.Effects of high-frequency repetitive transcranial magnetic stimulation on central facial paralysis after ischemic stroke
Hui ZHU ; Young XIA ; Zunke GONG ; Shin WANG ; Ke MA ; Jinqiu YAN
Chinese Journal of Rehabilitation Theory and Practice 2022;28(2):199-203
Objective To explore the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) on central facial paralysis after ischemic stroke. Methods From June, 2020 to June, 2021, 54 patients with central facial palsy after ischemic stroke who were hospitalized in the Rehabilitation Department of Xuzhou Central Hospital were randomly divided into control group (n = 27) and experimental group (n = 27). Both groups were given conventional rehabilitation treatment, including medication and facial muscle rehabilitation training. The experimental group was treated with 5 Hz rTMS on the affected primary motor cortex, and the control group was treated with the same parameters of sham stimulation at the same site. Before treatment and four weeks after treatment, the House-Brackmann Grading System 2.0 (HBGS-2), the Sunnybrook Facial Grading System, the horizontal distance difference between the bilateral mouth corners to the lower center of the philtrum at rest, the horizontal distance difference between the bilateral mouth corners to the intersection of the mandibular central incisor when showing the teeth at the best effort and the angle of the tongue midline deviating from the facial midline when the tongue was stretched out were used to evaluate the facial nerve function of the patient. Results One case dropped down in each group. Before treatment, there was no significant difference in the scores of HBGS-2 and Sunnybrook Facial Grading System, the horizontal distance difference between the bilateral mouth corners to the lower center of the philtrum at rest, the horizontal distance difference between the bilateral mouth corners to the intersection of the mandibular central incisor when showing the teeth at the best effort, and the angle of the tongue midline deviating from the facial midline when the tongue was stretched out between two groups (P > 0.05). After treatment, all the indexes significantly improved in both groups (|t| > 8.987, P < 0.001), and were better in the experimental group than in the control group (t > 2.939, P < 0.01). Conclusion 5 Hz rTMS on the affected primary motor cortex is effective on the facial nerve function of patients with central facial palsy after ischemic stroke.