Mitochondrial Dysfunction Promotes Breast Cancer Cell Migration and Invasion through HIF1α Accumulation via Increased Production of Reactive Oxygen Species

Although mitochondrial dysfunction has been observed in various types of human cancer cells, the molecular mechanism underlying mitochondrial dysfunction mediated tumorigenesis remains largely elusive. To further explore the function of mitochondria and their involvement in the pathogenic mechanisms of cancer development, mitochondrial dysfunction clones of breast cancer cells were generated by rotenone treatment, a specific inhibitor of mitochondrial electron transport complex I. These clones were verified by mitochondrial respiratory defect measurement. Moreover, those clones exhibited increased reactive oxygen species (ROS), and showed higher migration and invasive behaviors compared with their parental cells. Furthermore, antioxidant N-acetyl cysteine, PEG-catalase, and mito-TEMPO effectively inhibited cell migration and invasion in these clones. Notably, ROS regulated malignant cellular behavior was in part mediated through upregulation of hypoxia-inducible factor-1 α and vascular endothelial growth factor. Our results suggest that mitochondrial dysfunction promotes cancer cell motility partly through HIF1α accumulation mediated via increased production of reactive oxygen species

Arsenic Trioxide Inhibits Cell Growth and Induces Apoptosis through Inactivation of Notch Signaling Pathway in Breast Cancer

Arsenic trioxide has been reported to inhibit cell growth and induce apoptotic cell death in many human cancer cells including breast cancer. However, the precise molecular mechanisms underlying the anti-tumor activity of arsenic trioxide are still largely unknown. In the present study, we assessed the effects of arsenic trioxide on cell viability and apoptosis in breast cancer cells. For mechanistic studies, we used multiple cellular and molecular approaches such as MTT assay, apoptosis ELISA assay, gene transfection, RT-PCR, Western blotting, and invasion assays. For the first time, we found a significant reduction in cell viability in arsenic trioxide-treated cells in a dose-dependent manner, which was consistent with induction of apoptosis and also associated with down-regulation of Notch-1 and its target genes. Taken together, our findings provide evidence showing that the down-regulation of Notch-1 by arsenic trioxide could be an effective approach, to cause down-regulation of Bcl-2, and NF-κB, resulting in the inhibition of cell growth and invasion as well as induction of apoptosis. These results suggest that the anti-tumor activity of arsenic trioxide is in part mediated through a novel mechanism involving inactivation of Notch-1 and its target genes. We also suggest that arsenic trioxide could be further developed as a potential therapeutic agent for the treatment of breast cancer

Chemoresistance to gemcitabine in hepatoma cells induces epithelial-mesenchymal transition and involves activation of PDGF-D pathway

Hepatocellular carcinoma (HCC) is one of the common malignances in the world and has high mortality in part due to development of acquired drug resistance. Therefore, it is urgent to investigate the molecular mechanism of drug resistance in HCC. To explore the underlying mechanism of drug resistance in HCC, we developed gemcitabine-resistant (GR) HCC cells. We used multiple methods to achieve our goal including RT-PCR, Western blotting analysis, transfection, Wound-healing assay, migration and invasion assay. We observed that gemcitabine-resistant cells acquired epithelial-mesenchymal transition (EMT) phenotype. Moreover, we found that PDGF-D is highly expressed in GR cells. Furthermore, down-regulation of PDGF-D in GR cells led to partial reversal of the EMT phenotype. Our findings demonstrated that targeting PDGF-D could be a novel strategy to overcome gemcitabine resistance in HCC

Effects of urease and nitrification inhibitors on soil N, nitrifier abundance and activity in a sandy loam soil

Inhibitors of urease and ammonia monooxygenase can limit the rate of conversion of urea to ammonia and ammonia to nitrate, respectively, potentially improving N fertilizer use efficiency and reducing gaseous losses. Winter wheat grown on a sandy soil in the UK was treated with urea fertilizer with the urease inhibitor N-(n-butyl) thiophosphoric triamide (NBPT), the nitrification inhibitor dicyandiamide (DCD) or a combination of both. The effects on soil microbial community diversity, the abundance of genes involved in nitrification and crop yields and net N recovery were compared. The only significant effect on N-cycle genes was a transient reduction in bacterial ammonia monooxygenase abundance following DCD application. However, overall crop yields and net N recovery were significantly lower in the urea treatments compared with an equivalent application of ammonium nitrate fertilizer, and significantly less for urea with DCD than the other urea treatments

Xia, J.; et al., Arsenic Trioxide Inhibits Cell Growth and Induces Apoptosis through Inactivation of Notch Signaling Pathway in Breast Cancer. Int. J. Mol. Sci. 2012, 13, 9627–9641

The authors wish to change Figure 5D of the paper published in IJMS [1]. In Figure 5D, the bands for NF-κB and Bcl-2 are similar with Notch-1 bands. The authors have carefully checked the original files and found that it is an inadvertent mistake in the published version of Figure 5D. Figure 5 is revised as follows. The authors would like to apologize for any inconvenience caused to the readers by these changes.[...

Synapsis and Meiotic Recombination in Male Chinese Muntjac (Muntiacus reevesi)

The muntjacs (Muntiacus, Cervidae) have been extensively studied in terms of chromosomal and karyotypic evolution. However, little is known about their meiotic chromosomes particularly the recombination patterns of homologous chromosomes. We used immunostained surface spreads to visualise synaptonemal complexes (SCs), recombination foci and kinetochores with antibodies against marker proteins. As in other mammals pachytene was the longest stage of meiotic prophase. 39.4% of XY bivalents lacked MLH1 foci compared to less than 0.5% of autosomes. The average number of MLH1 foci per pachytene cell in M. reevesi was 29.8. The distribution of MLH1 foci differed from other mammals. On SCs with one focus, the distribution was more even in M. reevesi than in other mammals; for SCs that have two or more MLH1 foci, usually there was a larger peak in the sub-centromere region than other regions on SC in M. reevesi. Additionally, there was a lower level of interference between foci in M. reevesi than in mouse or human. These observations may suggest that the regulation of homologous recombination in M. reevesi is slightly different from other mammals and will improve our understanding of the regulation of meiotic recombination, with respect to recombination frequency and position

Assessing China's agricultural water use efficiency in a green-blue water perspective : a study based on data envelopment analysis

Uneven water resources and growing food demand due to an increasing population bring challenges to China. One important mechanism to address these challenges is to enhance water use efficiency (WUE). This requires information on current efficiencies in water use for agricultural production. In this study, we provide a benchmarking tool to assess relative agricultural WUE in 31 provinces in China during 2003-2013. Data Envelopment Analysis (DEA) was used with both green-blue water and blue-only scenarios. Results show that China’s agricultural WUE has improved evidently after 2008. Overall technical efficiency (TE) and the pure technical efficiency (PTE) in China based on the green-blue scenario are relatively high, with the average potential increase less than 10% (8% and 4%, respectively). However, there is a larger potential for blue water use efficiency (14% and 7% respectively). The PTE in Northern China (NC) is higher than that in Southern China (SC) while the TE in NC is lower under green-blue scenario. Moreover, the TE and PTE in NC are lower than that in SC under blue-only scenario. These results indicate that green water management techniques in NC are superior to SC but the scale efficiency (SE) in NC is lower. There are four provinces where the efficiency values are on the frontier in four cases, i.e. two scenarios (green-blue and blue-only) and two assumptions in DEA, but fourteen provinces where the efficiency values are not on the frontier in any case and most of them were located in SC. Our results also suggest that improving SE can substantially contribute to national WUE, but exploring the solutions to enhance blue water use efficiency in China is also a key task in the future works. The research results have important implications for China and different provinces to improve agricultural WUE by water policies and management