Engeletin suppresses cervical carcinogenesis in vitro and in vivo by reducing NF-κB-dependent signaling.

Cervical cancer is an aggressive human cancer with poor prognosis among women, and urgently requires effective treatments. Engeletin (ENG, dihydrokaempferol 3-rhamnoside), as a flavanonol glycoside, could be found in various kinds of vegetables and fruits, exerting significant anti-inflammatory biological activities. However, its role in regulating cervical cancer, as well as the underlying molecular mechanisms are still unknown. In this study, we found that ENG treatments dose-dependently reduced the proliferation of cervical cancer cells. Epithelial to mesenchymal transition (EMT) process in cervical cancer was also restrained by ENG using transwell analysis, as evidenced by the significantly reduced migration and invasion. In addition, ENG treatments restricted vascular endothelial growth factor-A (VEGFA) expression in cervical cancer cells, contributing to the suppression of angiogenesis. Mechanistically, ENG significantly reduced the expression of chemokine (C-C motif) ligand 2 (CCL2) in cervical cancer cells associated with the blockage of nuclear factor-κB (NF-κB) signaling pathway. Moreover, ENG functioned as an inhibitor of NF-κB, which was involved in the repression of angiogenesis. In xenograft model, ENG treatment effectively reduced the tumor volume and weight, accompanied with decreased expression of phosphorylated NF-κB, CCL2 and VEGFA, and showed little influence on the body weight change. Therefore, ENG might be a potential therapeutic strategy for the treatment of cervical cancer.

Apoptotic cell death induced by Z-Ligustilidein human ovarian cancer cells and role of NRF2.

Z-Ligustilide is the most potent bioactive component of Angelica sinensis, which is widely used in Chinese traditional medicine. Z-Ligustilide selectively affected ovarian cancer cell survival in a dose dependent manner. Z-Ligustilide induced apoptotic cell death was determined by flow cytometry. We also demonstrated that apoptotic cell death was triggered by Z-Ligustilideinduced oxidative stress and mitochondria played an active role. Mitochondrial polarization was reduced by Z-Ligustilidewhereas mitochondrial superoxide formation was increased. NRF2 was induced by Z-Ligustilide in OVCAR-3 cells at epigenetic level and its downstream antioxidant defense genesHeme oxygenase-1,NAD(P)H Quinone Dehydrogenase 1, UDP Glucuronosyltransferase Family 1 Member A1and Glutamate-Cysteine Ligase. NRF2 knockdown by siRNA resulted increased cell death by Z-Ligustilide in ovarian cancer cells. Our result demonstrated the pro-survival role of NRF2 in Z-Ligustilide induced ovarian cancer cell death.

Correlation analysis of urine metabolites and clinical staging in patients with ovarian cancer.

This study is to investigate the correlation between urine metabolites and clinical staging in patients with ovarian cancer. The urina sanguinis from 56 cases of primary epithelial ovarian cancer patients and 15 healthy volunteers was collected and the urine metabolites were extracted. Ultra high performance liquid chromatography/time-of-flight mass spectrometry (UPLC-Q-TOF-MS) analysis was performed. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were used to analyze the mass spectrometry data. Database retrieval and comparison of the screened metabolites were performed and one-way ANOVA and least significant difference (LSD) t test were carried out. PCA analysis of UPLC-Q-TOF-MS results showed that the score plots of samples from healthy people and patients with ovarian cancer at different clinical stages were separated. Further PLS-DA analysis significantly improved the classification results. The R(2)X was 0.757, the R(2)Y was 0.977 and the Q(2)Y was 0.87, indicating that the model stability and predictability were good. Eight metabolites, including N-acetylneuraminic acid-9-phosphate, 5'-methioadenosine, uric acid-3-nucleoside, pseudouridine, L-valine, succinic acid, L-proline and ß-nicotinamide mononucleotide were identified. The contents of these metabolites increased with the development of the disease. There was correlation between urine metabolites and clinical staging in patients with ovarian cancer.

Different effects of H2O2 treatment on cervical squamous carcinoma cells and adenocarcinoma cells.

INTRODUCTION: This study aims to compare the antioxidant abilities of cervical squamous carcinoma cells and cervical adenocarcinoma cells and to study the related mechanisms. MATERIAL AND METHODS: Cervical squamous carcinoma and adenocarcinoma cells were treated with H2O2. Cell proliferation was determined with the MTT assay. The reactive oxygen species (ROS) level was detected by the 2',7'-dichlorofluorescein-diacetate (DCFH-DA) method. The 5,5'-dithiobis-2-nitrobenzoic acid (DTNB) method was performed to measure intracellular concentrations of reduced glutathione (GSH) and oxidized glutathione (GSSG). The nitrite formation method, the molybdate colorimetric method, and the DTNB colorimetric method were used to determine activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), respectively. RESULTS: Compared with untreated control cells, cell proliferation of cervical squamous carcinoma cells and cervical adenocarcinoma cells was significantly inhibited by H2O2 treatment (p < 0.05). Reactive oxygen species levels and GSSG levels were significantly increased (p < 0.01), whereas GSH levels were significantly decreased (p < 0.05 or 0.01) in both cells after H2O2 treatment. Thus the ratio of GSH/GSSG was significantly decreased by H2O2 treatment in both cells (p < 0.01). In addition, H2O2 treatment significantly increased activities of SOD, CAT, and GPx in both cells (p < 0.05 or 0.01). Furthermore, the above-mentioned changes induced by H2O2 treatment were more dramatic in cervical squamous carcinoma cells. CONCLUSIONS: The antioxidant ability of cervical squamous carcinoma cells is lower than that of cervical adenocarcinoma cells, which may be related to the increased ROS levels in cervical squamous carcinoma cells induced by H2O2 treatments.