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Here, we investigate the apoptotic effect of allicin, the predominant component of freshly crushed garlic, on neuroblastoma cells. In this paper, the authors have first assessed the effect of allicin on human neuroblastoma SK-N-SH cells and then investigated the underlying mechanism. The results indicate that allicin suppresses SK-N-SH cell growth in a dose-dependent and time-dependent manner and that 5 μmol/l of allicin leads to a significant increase in apoptotic rate with annexin-V/PI double staining. Western blot analysis shows that treatment with allicin-induced apoptosis through activation of caspases-3 and 9. Phosphorylation of p38 MAPK contributes to allicin-induced apoptosis upstream of caspase activation. Using p38 MAPK inhibitor, the authors discovered that p38 MAPK activation subsequently induces the release of cytochrome-c from mitochondria into the cytosol. Taken together, the results demonstrate that allicin can activate the p38 MAPK pathway, which leads to mitochondrial release of cytochrome-c, thus inducing SK-N-SH cell apoptosis. Overall, this study suggests that allicin may be used as one of the novel pharmacological treatment strategies in neuroblastoma. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Source


Hao E.,Shandong University | Lang F.,Shandong University | Chen Y.,Peoples Hospital of Rizhao | Zhang H.,Shandong University | And 3 more authors.
PLoS ONE | Year: 2013

Background/Aims:Septic cardiomyopathy is a severe condition that remains a challenge for clinical management. This study investigated whether the natural polyphenolic compound resveratrol could be used as a prophylactic treatment to alleviate sepsis-related myocardial injury; the underlying molecular mechanisms were deciphered by both in vitro and in vivo experiments.Methods:A mouse model of endotoxin-induced cardiomyopathy was developed by intraperitoneal injection of LPS, and resveratrol was administered prophylatically to the animals. Serum LDH and CK activities were measured to detect myocardial injury, and echocardiography was performed to monitor cardiac structure and function. Various cytokines/chemokines and the Nrf2 antioxidant defense system were examined in the heart tissue. The effects of resveratrol on LPS-induced Nrf2 activation, ROS generation, and apoptotic cell death were further investigated in cultured primary human cardiomyocytes. An Nrf2 specific siRNA was used to define its role in resveratrol-mediated cardiomyocyte protective effect.Results:Resveratrol pretreatment significantly attenuated LPS-induced myocardial injury in mice, which was associated with suppressed proinflammatory cytokine production and enhanced Nrf2 activation in the heart. In cultured primary human cardiomyocytes, resveratrol activated Nrf2, inhibited LPS-induced ROS generation, and effectively protected the cells from LPS-induced apoptotic cell death. Knockdown of Nrf2 abrogated resveratrol-mediated protection of the cells from LPS-induced cell death.Conclusion:Resveratrol effectively alleviates endotoxin-induced cardiac toxicity through mechanisms that involve the Nrf2 antioxidant defense pathway. Our data suggest that resveratrol might be developed as a useful prophylactic management for septic cardiomyopathy. © 2013 Hao et al. Source


Zhao J.-X.,Qingdao University | Liu H.,Peoples Hospital of Rizhao | Lv J.,Qingdao University | Yang X.-J.,Qingdao University
European Review for Medical and Pharmacological Sciences | Year: 2014

OBJECTIVE: The PI3K/Akt signaling pathway is constitutively activated in some ovarian cancers; when activated, it promotes invasion and inhibits chemotherapy-mediated apopto-sis in cancer cells.The fungal metabolite wortman-nin is the currently known inhibitors that show fairly high specificity for PI3K.We examined whether PI3K/Akt activity correlates with invasion and apoptotic resistance to chemotherapy in cultured human ovarian cancer cells, and whether inhibition of PI3K/Akt by wortmannin inhibits invasion and enhances cisplatin-induced apoptosis in cultured human ovarian cancer cells. MATERIALS AND METHODS: The cisplatin-sensitive A2780 ovarian adenocarcinoma cell line and its daughter line, A2780cis was evaluated for basal Akt activity. Chemotherapy-induced cell death was evaluated following down-regulation of Akt activity by wortmannin treatment or upregulation of Akt activity by myr-Akt treatment. Invasion and migration were assessed using Boyden chamber assays RESULTS: Inhibiting or activation of PI3K/Akt signaling pathway by wortmannin had little effect on the basal level of apoptosis in ovarian cancer cells, but increased the apoptotic effect of chemotherapy in A2780cis cells, decreased the apoptotic effect of chemotherapy in cis-platin-sensitive A2780 cells. Cisplatin resistant cells display increased potential for migration and invasion. CONCLUSIONS: The antiapoptotic effect of AKT activation in ovarian cancer cells confer invasive ability and resistance to apoptosis. Wort-mannin is as adjuncts to conventional chemotherapy in the treatment of ovarian cancer. Source


Wang C.,Shandong University | Jiang Y.,Shandong University | Li X.,Peoples Hospital of Rizhao | Hu L.,Shandong University
Breast Cancer | Year: 2015

Background: Gold nanoparticles (GNPs) have been conceived to cause increased cytotoxicity of radiotherapy in human malignant cells. Greater uptake of GNPs by cells may induce increased radiation effects. Here we report the radiosensitization effect of glucose-capped GNPs (Glu-GNPs) with different sizes (16 nm and 49 nm) on MDA-MB-231 cells in the presence of megavoltage X-rays. Methods: Transmission electron microscopy (TEM) was used to observe the distribution of Glu-GNPs in cells. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) was used to measure the quantities of Glu-GNPs absorbed by cells. After treatment of Glu-GNPs with a series of concentrations, we used the MTT and clonogenic assays to confirm the radiation enhancement effect of Glu-GNPs on MDA-MB-231 cells. The cell cycle distribution was analyzed by flow cytometry to further explore the mechanisms of enhanced radiosensitivity of Glu-GNPs. Results: TEM showed that Glu-GNPs are mainly distributed in the cytoplasm of cells, including endosomes and lysosomes. ICP-AES indicates that MDA-MB-231 cells absorb more 49-nm Glu-GNPs than 16-nm Glu-GNPs in number (P < 0.05). Glu-GNPs have little cytotoxicity toward MDA-MB-231 cells with a concentration below 20 nM. In the clonogenic assay, the combination of Glu-GNPs with radiation induced a significant growth inhibition, compared with radiation alone (P < 0.05). Moreover 49-nm Glu-GNPs induced much greater radiation effects than 16-nm Glu-GNPs (P < 0.05). Flow cytometry shows that Glu-GNPs can help radiation arrest more cells in the G2/M phase, with greater effect with 49-nm Glu-GNPs than 16-nm Glu-GNPs. Conclusions: Glu-GNPs can increase the cytotoxicity of radiation toward MDA-MB-231 cells, probably by regulating the distribution of the cell cycle, with more cells in the G2/M phase. The effect of radiation enhancement may be related to the quantities of Glu-GNPs in the cells. © 2013, The Japanese Breast Cancer Society. Source


Xu C.-D.,Peoples Hospital of Rizhao
Asian Pacific Journal of Cancer Prevention | Year: 2014

Objective: To explore the clinical effects of nimotuzumab combined with chemotherapy in the treatment of late gastric cancer. Methods: A total of 34 reoccurrence or metastatic patients with late stage gastric cancer who were confirmed by histopathology and/or cytology were selected and randomly divided into observational and control groups, of 17 cases each. Patients in the control group were treated with the standard DCF plan, while patients in observational group additionally received nimotuzumab. The short-term and long-term efficacy and adverse reactions in the 2 groups were followed. Results: The objective response rate (ORR) and disease control rate (DCR) were 64.7% (11/17) and 82.4% (14/17) in observational group and 25.0%(4/16) and 37.5%(6/16) in the control group(ORR and DCR between 2 groups, χ2 = 5.2412, P = 0.0221 and χ2 = 6.9453, P = 0.0084). The median progression-free survival (PFS) time and median overall survival (OS) time were 6.50 months and 12.50 months in observational group and 4.50 months and 8.25 months in the control group (P = 0.0212; P = 0.0255). The main toxic and side effects in the 2 groups were reduced leukocytes and hemoglobin, gastrointestinal reactions and hair loss and these were relieved after symptomatic treatment and nutrition support therapy. There were no differences in the occurrence of toxic and side effects between the 2 groups. Conclusions: Nimotuzumab combined with DCF plan is effective in treating late stage gastric cancer. A larger scale study is now warranted for confirmation of the findings. Source

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