Center of Experimental Medicine, Wuhan First Hospital, Wuhan City, People’s Republic of China.

Human colon cancer is the leading cause of cancer death in both men and women worldwide. The c-Myc gene is frequently deregulated and overexpressed in this malignancy, and strategies designed to inhibit c-Myc expression in cancer cells may have considerable therapeutic value. We design and use short hairpin RNA (shRNA) to inhibit c-Myc expression in Colo 320 cells and validat its effect on cell proliferation. In this study, four c-Myc-shRNA expression vectors were constructed and introduced into Colo 320 cells, and the cell cycle and apoptotic cells were analyzed by flow cytometry. The effects of c-Myc silencing on tumor-cell growth was assessed by the soft agar assay and by DNA synthesis experiments. Expression of c-Myc was also assessed by real-time reverse transcription polymerase chain reaction and Western blot analysis. Upon transient transfection with plasmid-encoding shRNA, it was found that expression of c-Myc decreased in shRNA-transfected cells, and the downregulation of c-Myc inhibited cell growth and induced apoptosis in Colo 320 cells. c-Myc downregulation also increased cell population in the G0-G1 phase. In conclusion, our findings demonstrate that shRNA can inhibit the DNA replication and induce apoptosis in Colo 320 cells effectively and, therefore, could be used as a new potential anticancer tool for the therapy of human colon cancer.

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Molecular and Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, P.O.B. 63, 00014 Helsinki, Finland. tatiana.petrova@helsinki.fi

The Drosophila transcription factor Prospero functions as a tumor suppressor, and it has been suggested that the human counterpart of Prospero, PROX1, acts similarly in human cancers. However, we show here that PROX1 promotes dysplasia in colonic adenomas and colorectal cancer progression. PROX1 expression marks the transition from benign colon adenoma to carcinoma in situ, and its loss inhibits growth of human colorectal tumor xenografts and intestinal adenomas in Apc(min/+) mice, while its transgenic overexpression promotes colorectal tumorigenesis. Furthermore, in intestinal tumors PROX1 is a direct and dose-dependent target of the beta-catenin/TCF signaling pathway, responsible for the neoplastic transformation. Our data underscore the complexity of cancer pathogenesis and implicate PROX1 in malignant tumor progression through the regulation of cell polarity and adhesion.

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Division of Population Science, Fox Chase Cancer Center, 510 Township Line Road, 1st floor, Cheltenham, PA 19012, United States.

OBJECTIVE: This study examined the prevalence and correlates of U.S. adults’ awareness of the role that physical activity plays in preventing colon cancer. METHODS: Data were analyzed for 1932 respondents to the Health Information National Trends Survey who answered a question about factors that reduce the chances of getting colon cancer. Individuals who listed physical activity in response to this question were denoted as being aware of its role in colon cancer prevention. RESULTS: Few respondents (15.0%) listed physical activity as a means of reducing colon cancer risk. Awareness was especially low among individuals aged 50 years and over, those with lower levels of education, individuals who believe that physical activity recommendations are confusing, those reporting less exposure to information about physical activity and cancer, individuals who did not report looking for information about cancer, those with poorer knowledge of colon cancer symptoms, and less physically active individuals. CONCLUSIONS: There is poor awareness among U.S. adults of the role that physical activity plays in preventing colon cancer. PRACTICE IMPLICATIONS: Health care providers should routinely inform their patients that engaging in regular physical activity greatly reduces the risk of developing colon cancer.

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Department of Surgery and Pharmacology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.

The aim of this study was to investigate the effect of quercetin, a flavonoid, on the apoptotic pathway in a human prostate cell line (LNCaP). We observed that treatment of cells for 24h with quercetin-induced cell death in a dose-dependent manner. A sustained inhibition of the major survival signal, Akt, occurred in quercetin-treated cells. Treatment of LNCaP cells with an apoptosis inducing concentration of quercetin (100muM) resulted in a rapid decrease in the inhibitory Ser((473)) phosphorylation of Akt leading to inhibition of its kinase activity. Quercetin treatment (100muM) also caused a decrease in Ser((136)) phosphorylation of Bad, which is a downstream target of Akt. Protein interaction assay revealed that during treatment with quercetin, Bcl-xL dissociated from Bax and then associated with Bad. Our results also show that quercetin decreases the Bcl-xL:Bax ratio and increases translocation and multimerization of Bax to the mitochondrial membrane. The translocation is accompanied by cytochrome c release, and procaspases-3, -8 and -9 cleavage and increased poly(ADP-ribose) polymerase (PARP) cleavage. Similar results were observed in human colon cancer HCT116Bax(+/+) cell line, but not HCT116Bax(-/-) cell line. Interestingly, at similar concentrations (100muM), quercetin treatment did not affect the viability or rate of apoptosis in normal human prostate epithelial cell line (PrEC) and rat prostate epithelial cell line (YPEN-1). Our results indicate that the apoptotic processes caused by quercetin are mediated by the dissociation of Bax from Bcl-xL and the activation of caspase families in human prostate cancer cells.

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Department of Medicine, University of Toronto, Canada; Department of Physiology, University of Toronto, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Canada; Division of Cell and Molecular Biology, Toronto General Research Institute, University Health Network, 10-354, Toronto Medical Discovery Tower, The MaRS Building, 101 College Street, Toronto, Ontario, Canada M5G 1L7.

Type II diabetes mellitus (T2D) develops as the consequence of relative insulin insufficiency. The onset of T2D is characterized by insulin resistance, and in most cases, with hyperinsulinemia for compensation. Extensive basic and clinical examinations have identified a large profile of T2D susceptibility genes and multiple risk factors, including obesity and sedentary life style, which are shared by colon cancer development. The intestinal endocrine L cells produce an incretin hormone, namely glucagon-like peptide-1 (GLP-1), which stimulates insulin secretion in blood glucose dependent manner, pancreatic beta cell proliferation and neogenesis. It has been shown that in T2D patients, postprandial GLP-1 secretion level is reduced. I hypothesize that during the development of insulin resistance, intestinal endocrine L cells produce more GLP-1 for compensation. This compensatory response involves the activation of Wnt signaling pathway and the cross-talk between Wnt and insulin signaling pathways. A pathological consequence of this compensation will be the stimulated expression of proto-oncogenes, including c-Myc.

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