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Wild-type p53-induced phosphatase (Wip1) is a member of the protein phosphatase type 2C family and is an established oncogene due to its dephosphorylation of several tumor suppressors and negative control of the DNA damage response system. It has been reported to dephosphorylate p53, ataxia telangiectasia mutated, checkpoint kinase 1 and p38 mitogen activated protein kinases, forming negative feedback loops to inhibit apoptosis and cell cycle arrest. Wip1 serves a major role in tumorigenesis, progression, invasion, distant metastasis and apoptosis in various types of human cancer. Therefore, it may be a potential biomarker and therapeutic target in the diagnosis and treatment of cancer. Furthermore, previous evidence has revealed a new role for Wip1 in the regulation of chemotherapy resistance. In the present review, the current knowledge on the role of Wip1 in cancer is discussed, as well as its potential as a novel target for cancer treatment and its function in chemotherapy resistance. [ABSTRACT FROM AUTHOR]

Loss of sirtuin 1 (SIRT1) activity may be associated with metabolic diseases, including diabetes. The aim of the present study was to investigate the potential effects of overexpressed endothelial nitric oxide synthase (eNOS) on cell proliferation and apoptosis with SIRT1 activation in the Min6 mouse pancreatic ß cell line. A pcDNA3.0-eNOS plasmid was constructed and transfected into Min6 cells for 24 h prior to harvesting. eNOS expression was validated and SIRT1 expression was detected following plasmid transfection using reverse transcription-quantitative polymerase chain reaction and western blot analysis, which demonstrated that the expression levels of eNOS and SIRT1 were significantly upregulated. Furthermore, the cell proliferation and cell apoptosis of the Min6 cells were evaluated, using a cell counting kit-8 assay and flow cytometry, respectively. The results suggested that overexpressed eNOS promoted cell proliferation and inhibited cell apoptosis in Min6 cells. The interaction between eNOS and SIRT1 was explored through co-immunoprecipitation, and it found that there was a strong interaction between eNOS and SIRT1. In conclusion, overexpressed eNOS may induce SIRT1 activation, which is implied to play a protective role in Min6 cells, and eNOS may be a new therapeutic target for diseases such as type 2 diabetes. [ABSTRACT FROM AUTHOR]

Zoledronic acid (ZOL), a nitrogen-containing bisphosphonate, is widely used in metastatic bone disease. Previous studies indicate that ZOL has marked anti-leukemia activity, however, the underlying mechanism of action remains to be elucidated. The present study aimed to explore the mechanism of the anti-leukemia effect of ZOL in leukemia cells. It was observed that ZOL inhibited the proliferation of HL-60 and adriamycin-resistant HL-60 (HL-60/A) cells using a WST-8 assay. An Annexin V-propidium iodide indicated that ZOL induced apoptosis of the two cell types in a dose- and time-dependent manner. Hoechst 33342 staining was also used to verify the levels of apoptosis. The colony formation assay demonstrated that ZOL significantly inhibited colony formation capacity in acute myeloid leukemia (AML) cells. This was achieved by the induction of S-phase cell cycle arrest, downregulation of B-cell lymphoma 2 (Bcl-2) and upregulation of Bcl-2 associated X protein and cleaved poly (ADP-ribose) polymerase. The results indicate that ZOL inhibited cell proliferation by inducing apoptosis via the mitochondrial apoptotic pathway and this anti-leukemic activity appeared notably enhanced in HL-60/A cells. As ZOL is already available for clinical use, these results indicate that it may be an effective addition to the chemotherapeutic strategies for AML. [ABSTRACT FROM AUTHOR]