• Title/Summary/Keyword: glutathione-s-transferase (GST)

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Sensitivity of Gastric Cancer Cells to Chemotherapy Drugs in Elderly Patients and Its Correlation with Cyclooxygenase-2 Expression

  • Qiu, Zhen-Qin;Qiu, Zhen-Rong
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.8
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    • pp.3447-3450
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    • 2015
  • Objective: To explore the sensitivity of gastric cancer cells to chemotherapy drugs in elderly patients and its correlation with cyclooxygenase-2 (COX-2) expression in cancer tissue. Materials and Methods: Forty-three elderly patients with gastric cancer (observation group) and 31 young patients with gastrointestinal tumors (control group) who were all diagnosed by pathology and underwent surgery in the 89th Hospital of Chinese People's Liberation Army were selected. Drug sensitivity testing of tumor cells in primary culture was carried out in both groups using a methyl thiazolyl tetrazolium (MTT) method, and the expression of COX-2 and the factors related to multi-drug resistance (MDR) in cancer tissue were assessed by immunohistochemistry. Results: The inhibition rates (IR) of vincristine (VCR), 5-fluorouracil (5-FU), oxaliplatin (L-OHP), mitomycin (MMC) and epirubicin (eADM) on tumor cells in the observation group were dramatically lower than in the control group, with statistical significance (P<0.05 or P<0.01). The positive rates of COX-2, glutathione s-transferase-${\pi}$ (GST-${\pi}$) and P glycoprotein (P-gp) expression in cancer tissue in the observation group were all higher than in control group (P<0.05), while that of DNA topoisomerase $II{\alpha}$ ($TopoII{\alpha}$) expression lower than in the control group (P<0.01). In the observation group, COX-2 expression in cancer tissue had a significantly-positive correlation with GST-${\pi}$ and P-gp (r=0.855, P=0.000; r=0.240, P=0.026), but a negative correlation with $TopoII{\alpha}$ (r=-0.328, P=0.002). In the control group, COX-2 expression in cancer tissue was only correlated with P-gp positively (r=0.320, P=0.011). Bivariate correlation analysis displayed that COX-2 expression in cancer tissue in the observation group had a significantly-negative correlation with the IRs of 5-FU, L-OHP, paclitaxel (PTX) and eADM in tumor cells (r=-0.723, P=0.000; r=-0.570, P=0.000; r=-0.919, P=0.000; r=-0.781, P=0.000), but with hydroxycamptothecine (HCPT), VCR and 5-FU in the control group (r=-0.915, P=0.000; r=-0.890, P=0.000; r=-0.949, P=0.000). Conclusions: Gastric cancer cells in elderly patients feature stronger MDR, which may be related to high COX-2 expression.

APP Tail 1 (PAT1) Interacts with Kinesin Light Chains (KLCs) through the Tetratricopeptide Repeat (TPR) Domain (APP tail 1 (PAT1)과 kinesin light chains (KLCs)의 tetratricopeptide repeat (TPR) domain을 통한 결합)

  • Jang, Won Hee;Kim, Sang-Jin;Jeong, Young Joo;Jun, Hee Jae;Moon, Il Soo;Seog, Dae-Hyun
    • Journal of Life Science
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    • v.22 no.12
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    • pp.1608-1613
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    • 2012
  • A conventional kinesin, KIF5/Kinesin-I, transports various cargoes along the microtubule through interaction between its light chain subunit and the cargoes. Kinesin light chains (KLCs) interact with many different cargoes using their tetratricopeptide repeat (TPR) domain, but the mechanism underlying recognition and binding of a specific cargo has not yet been completely elucidated. We used the yeast two-hybrid assay to identify proteins that interact with the TPR domain of KLC1. We found an interaction between the TPR domain of KLC1 and an amyloid precursor protein (APP)-binding protein PAT1 (protein interacting with APP tail 1). The yeast two-hybrid assay demonstrated that the TPR domain-containing region of KLC1 mediated binding to the C-terminal tail region of PAT1. PAT1 also bound to KLC2 but not to kinesin heavy chains (KIF5A, KIF5B, and KIF5C) in the yeast two-hybrid assay. These protein-protein interactions were also observed in the glutathione S-transferase (GST) pull-down assay and by co-immunoprecipitation. Anti-PAT1 antibody as well as anti-APP anti-body co-immunoprecipitated KLC and KHCs associated with PAT1 from mouse brain extracts. These results suggest that PAT1 could mediate interactions between Kinesin-I and APP containing vesicles.

The Effect of Isoflavone and/or Grape Seed Oil Supplementation on Blood Lipid Profiles and Bone Strength in Ovariectomized Female Rats (이소플라본과 포도종실유의 보충이 난소절제 흰쥐의 혈중지질 패턴 및 골격강도에 미치는 영향)

  • 정혜경;최창숙;이지현;박원종;강명화
    • Journal of Nutrition and Health
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    • v.36 no.7
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    • pp.667-674
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    • 2003
  • The study was performed to investigate the effects of isoflavone and/or grape seed oil supplementation on serum and liver lipid profiles and bone strength in ovariectomized female rats. Female Spraque-Dawley rats were assigned into 4 groups of ovariectomized (O), isoflavone (0.085 mg/100 g b.w/day) in ovariectomized rats, grape seed oil in ovariectomized rats and isoflavone and/or grape seed oil in ovariectomized rats. After 8 weeks, biochemical profiles of serum, liver and bone were analyzed. Total food intakes, body weight gains and FER (food efficiency ratio) were not statistically significantly different among groups. Total cholesterol, triglyceride and LDL-cholesterol levels in serum were decreased by fed of isoflavone and/or grape seed oils. However, crude lipid and total cholesterol contents in liver were not affect of isoflavone and/or grape seed oil. The hepatic glutathione contents were increased by isoflavone and/or grape seed oil fed. The hepatic glutathione-S-transferase activity in isoflavone and/or grape seed oil supplemented groups were higher than that O group. Bone (scapular and femur bone) dry weight, femur of max weight and bending strength were no significant difference among groups. Our finding suggest that isoflavone/grape seed oils might have potential role for serum lipid profiles improvement and bone strength in vivo.

Induction of Apoptosis by Methanolic Extract of Rubia Cordifolia Linn in HEp-2 Cell Line is Mediated by Reactive Oxygen Species

  • Shilpa, P.N.;Sivaramakrishnan, V.;Devaraj, S. Niranjali
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2753-2758
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    • 2012
  • Rubia cordifolia Linn, which belongs to the Rubiaceae family, is a well-known herb used in Ayurvedic medicine. In the present study, we investigated the influence of a methanolic extract (RC) on the induction of apoptosis in HEp-2 (human laryngeal carcinoma) cell line, as evidenced by cytotoxicity, morphological changes and modification in the levels of pro-oxidants. Inhibition of cell proliferation and lactate dehydrogenase (LDH) release increased in a time and dose-dependent manner. Further, reduced glutathione (GSH), glutathione transferase (GST) and protein levels decreased and lipid peroxidation increased significantly on RC treatment in a dose dependent manner when compared to controls. Based on the results we determined the optimal dose as 30mg/ ml and the apoptotic effect of RC extract (30 mg/ml) on HEp-2 cells was confirmed by fluorescent microscopy and transmission electron microscopy (TEM) based on morphological and ultrastructural changes. RC extract suppressed the proliferation of HEp-2 oral cancer cells inducing apoptotic cell death in vitro. These results point to potential of RC extract as an agent for the treatment of laryngeal squamous cell carcinoma.

Chemopreventive Efficacy of Moringa oleifera Pods Against 7, 12-Dimethylbenz[a]anthracene Induced Hepatic Carcinogenesis in Mice

  • Sharma, Veena;Paliwal, Ritu;Janmeda, Pracheta;Sharma, Shatruhan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2563-2569
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    • 2012
  • Oxidative stress is a common mechanism contributing to initiation and progression of hepatic damage in a variety of liver disorders. Hence there is a great demand for the development of agents with potent antioxidant effect. The aim of the present investigation is to evaluate the efficacy of Moringa oleifera as a hepatoprotective and an antioxidant against 7, 12-dimethylbenz[a]anthracene induced hepatocellular damage. Single oral administration of DMBA (15 mg/kg) to mice resulted in significantly (p<0.001) depleted levels of xenobiotic enzymes like, cytochrome P450 and b5. DMBA induced oxidative stress was confirmed by decreased levels of reduced glutathione (GSH) and glutathione-S-transferase (GST) in the liver tissue. The status of hepatic aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) which is indicative of hepatocellular damage were also found to be decreased in DMBA administered mice. Pretreatment with the Moringa oleifera (200 and 400 mg/kg) orally for 14 days significantly reversed the DMBA induced alterations in the liver tissue and offered almost complete protection. The results from the present study indicate that Moringa oleifera exhibits good hepatoprotective and antioxidant potential against DMBA induced hepatocellular damage in mice that might be due to decreased free radical generation.

Antidiabetic and Antioxidative Effects of Corni fructus In Streptozotocin-Induced Diabetic Rats (산수유 추출물이 Streptozotocin으로 유발된 흰쥐의 항당뇨 및 항산화 작용에 미치는 효과)

  • Kim, Ok-Kyung
    • Journal of the Korean Applied Science and Technology
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    • v.22 no.2
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    • pp.157-167
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    • 2005
  • The extraction yield of Corni fructus was about 47.5% by extract apparatus. This study was done to investigate the antidiabetic and antioxidative effects of Corni fructus in Streptozotocin (STZ)-induced diabetic rats. The contents of serum glucose, total cholesterol and hepatic lipid peroxide, glutathione were significantly decreaed (p<0.05) in Corni fructus treated group compared to the those of STZ-control group, also content of triglyceride (TG), atherogenic index (AI) and activity of catalase were decreased, but not statistically significant. High density lipoprotein (HDL)-cholesterol and HDL-cholesterol/total cholesterol ratio (HTR) were increased in Corni fructus treated group compared to the those of STZ-control group. The activities of glutathione-S-transferase (GST) and superoxide dismutase (SOD) were significantly decreaed (p<0.05) in Corni fructus treated group compared to the those of STZ-control group. The content of hepatic glycogen and activities of glucose-phosphate dehydrogenase (G-6 PDH), glucokin-ase were significantly increased, but activity of glucose-Grphosphatase (G-6 Pase)was decreased in Corni fructus treated group compared to the those of STZ-control group. Therefore, these results indicated that ethanol extract of Corni fructus would have antidiabetic and antioxidative effects in STZ-induced diabetic rats.

The Hepatotoxicity and Testicular Toxicity Induced by Arecoline in Mice and Protective Effects of Vitamins C and E

  • Zhou, Jianhong;Sun, Qi;Yang, Zhirong;Zhang, Jie
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.2
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    • pp.143-148
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    • 2014
  • Arecoline is a major alkaloid of areca nuts which are widely chewed by southeast Asian and it manifests various toxic effects in different organs of human and animals. In this work, mature mice were treated by vitamins C plus E, arecoline, or both daily for four weeks. The results showed that arecoline significantly increased the levels of serum alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and significantly decreased the levels of reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) in the liver tissues. Additionally, the body weight, testis weight, sperm counts, motility and normal sperms also were significantly decreased. The supplement of vitamins C and E can bring the activities of ALP and GPT to normal levels and partially restore the sperm counts compared to the arecoline-treated group but have no other positive effects. In conclusion, the vitamins C and E partially attenuated the arecoline-induced hepatotoxiciy but basically had on protective effects against the arecoline-induced testicular toxicity.

Antidiabetic and Antioxidative Effects of Lycii fructus in Streptozotocin-Induced Diabetic Rats (Streptozotocin으로 유발된 흰쥐에 대한 구기자 추출물의 혈당강하 및 항산화 작용에 미치는 효과)

  • Kim, Ok-Kyung
    • Journal of the Korean Applied Science and Technology
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    • v.25 no.1
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    • pp.73-82
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    • 2008
  • This study was done to investigate the antidiabetic and antioxidant effects of Lycii fructus in Streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by intravenous injection of STZ at a dose 45mg/kg.b.w. dissolved in citrate buffer(pH4.5). The ethanol extract of Lycii fructus was orally administrated once a day for 7 days. The contents of serum glucose, total cholesterol were significantly decreaed (p<0.05) in Lycii fructus treated group compared to the those of STZ-control group, also content of Triglyceride (TG), Altherogenic index (AI) were decreased, but not statistically significant. But high density lipoprotein (HDL)-cholesterol and HDL-cholesterol/total cholesterol ratio (HTR) were increased in Lycii fructus treated group compared to the those of STZ-control group. The content of hepatic glycogen and activities of glucose-6-phosphate dehydrogenase(G-6PDH), glutathione-s-transferase(GST), superoxide dismutase(SOD) were significantly increased(p<0.05), glucose-6-phos-phatase(G-6pase)was significantly decreased(p<0.05) and The glutathione(GSH), glucokinase(GK) were increased. But not statistically significant In Lycii fructus treated group compared to the those of STZ-control group These results indicated that ethanol extract of Lycii fructus would have antidiabetic and antioxidant effects in STZ-induced diabetic rats.

Effects of Ovariectomy and Calcium Intake on Lipid Profile and Antioxidant Capacities in Rats (난소절제와 칼슘 섭취수준이 흰쥐의 지질패턴과 항산화능에 미치는 영향)

  • Choi, Mi-Kyeong;Kang, Myung-Hwa;Kim, Mi-Hyun
    • Journal of Nutrition and Health
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    • v.41 no.4
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    • pp.299-306
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    • 2008
  • The purpose of this research was to investigate the effect of the calcium intake on lipid profile and antioxidant capacities in ovariectomized (OVX) rats. Rats were divided into 3 groups and fed diet with different levels of calcium (low 0.1%, adequate 0.5%, high 1.5%) for 4 weeks. The half of rats in each group was ovariectomized and the others were sham-operated. And rats were fed same diets for 8 weeks after operation. Feed intake and weight gain were significantly higher in OVX group than those in sham-operated. Serum HDL-cholesterol was the highest in high-calcium group of OVX. Hepatic triglyceride of low-calcium group in sham-operated was the highest, while that of highcalcium group in OVX was the highest. Hepatic activities of glutathione-S-transferase (GST), glutathione peroxidase (GSH-Px), and catalase were significantly decreased by increasement of calcium intake. Hepatic TBARS level was the lowest in high-calcium group of OVX. And hepatic level of TBARS induced by AAPH was significantly decreased by increasement of calcium intake. These results may indicate that the high calcium intake have the potential role to improve lipid profiles and antioxidant capacities in OVX rats.