Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Berries have attracted attention for their chemopreventive activities in last a few years. Dietary freeze-dried blackberries have been shown to reduce esophagus and colon cancer development induced by chemical carcinogen in rodents. To elucidate molecular mechanisms involved in chemoprevention by berry extracts, we employed mouse epidermal Cl 41 cell line, a well-characterized in vitro model in tumor promotion studies. Pretreatment of Cl 41 cells with methanol-extracted blackberry fraction RO-ME resulted in a dramatical inhibition of B(a)PDE-induced activation of AP-1 and NFkB, and expression of VEGF and COX-2. The inhibitory effects of RO-ME on B(a)PDE-induced activation of AP-1 and NFkappaB appear to be mediated via inhibition of MAPKs and IkappaBalpha phosphorylation, respectively. In view of the important roles of AP-1, NFkappaB, VEGF and COX-2 in tumor promotion/progression, and VEGF and COX-2 are target of AP-1 and NFkappaB, we anticipate that the ability of black raspberries to inhibit tumor development may be mediated by impairing signal transduction pathways leading to activation of AP-1 and NFkappaB, subsequently resulting in down-regulation of VEGF and COX-2 expression. The RO-ME fraction appears to be the major fraction responsible for the inhibitory activity of black raspberries.
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PMID:Molecular mechanisms involved in chemoprevention of black raspberry extracts: from transcription factors to their target genes. 1680 Jul 74

The h-prune protein is a member of the DHH protein superfamily, and its overexpression in breast, colorectal and gastric cancers correlates with depth of invasion and degree of lymph-node metastasis. Taken together with the observation that h-prune is highly expressed in metastatic breast cancer, this suggests that h-prune can be used as a marker for the identification of subsets of cancer patients with highly aggressive tumours. H-prune possesses a phosphodiesterase (cAMP-PDE) activity, and inhibition of PDE activity with dipyridamole suppresses cell motility. H-prune interacts with nm23-H1, GSK-3beta and gelsolin. Although a correlation between an h-prune PDE activity and cellular motility has been shown, GSK-3beta does not affect the PDE activity of h-prune. Inhibition of the interactions between h-prune and GSK-3beta and nm23-H1 additively suppresses the migration of colon cancer and breast cancer cells, thus suggesting that h-prune regulates cell motility by two different means of action: through its PDE activity and in its interactions with protein partners. Therefore, the identification of highly specific inhibitors of h-prune should be useful in the development of drugs to treat cancer metastasis.
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PMID:Understanding h-prune biology in the fight against cancer. 1795 13

Phosphodiesterase 5 (PDE-5) is a major isoform of cGMP phosphodiesterase in diverse tissues and plays a critical role in regulating intracellular cGMP concentrations. However, the distribution and expression of PDE-5 in colitis-related colon cancer was still unclear, not even the function and mechanism. Western blotting and ELISA were performed to detect colonic PDE-5 expression in AOM/DSS-induced tumorigenesis model. Sildenafil, a specific PDE-5 inhibitor, was used to treat AOM/DSS-induced and AOM-induced colonic tumorigenesis model and DSS-induced colitis model. The leukocyte infiltration in colonic tissue was examined by flow cytometry and immunofluorescence staining. Further matrigel-based invasion assay was employed to determine the effects of Sildenafil on myeloid-derived suppressor cell (MDSC) in vitro. We first demonstrated the upregulation of colonic PDE-5 expression and the prevention role of PDE-5 inhibition in AOM/DSS-induced tumorigenesis model. More importantly, PDE-5 inhibitor Sildenafil inhibited colonic tumorigenesis dependent on inflammation and suppressed DSS-induced colitis. Molecular mechanism investigation indicated that Sildenafil regulated inflammation microenvironment via directly inhibiting MDSC infiltration in colonic tissue. The study provides solid evidence for the use of PDE-5 inhibitor in preventing and treating colonic inflammation-related tumorigenesis.
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PMID:Phosphodiesterase-5 inhibition suppresses colonic inflammation-induced tumorigenesis via blocking the recruitment of MDSC. 3066 14

Despite novel technologies, colon cancer remains undiagnosed and 25% of patients are diagnosed with metastatic colon cancer. Resistant to chemotherapeutic agents is one of the major problems associated with treating colon cancer which creates the need to develop novel agents targeting towards newer targets. A phosphodiesterase is a group of isoenzyme, which, hydrolyze cyclic nucleotides and thereby lowers intracellular levels of cAMP and cGMP leading to tumorigenic effects. Many in vitro and in vivo studies have confirmed increased PDE expression in different types of cancers including colon cancer. cAMP-specific PDE inhibitors increase intracellular cAMP that leads to activation of effector molecules-cAMP-dependent protein kinase A, exchange protein activated by cAMP and cAMP gated ion channels. These molecules regulate cellular responses and exert its anticancer role through different mechanisms including apoptosis, inhibition of angiogenesis, upregulating tumor suppressor genes and suppressing oncogenes. On the other hand, cGMP specific PDE inhibitors exhibit anticancer effects through cGMP dependent protein kinase and cGMP dependent cation channels. Elevation in cGMP works through activation of caspases, suppression of Wnt/b-catenin pathway and TCF transcription leading to inhibition of CDK and survivin. These studies point out towards the fact that PDE inhibition is associated with anti-proliferative, anti-apoptotic and anti-angiogenic pathways involved in its anticancer effects in colon cancer. Thus, inhibition of PDE enzymes can be used as a novel approach to treat colon cancer. This review will focus on cAMP and cGMP signaling pathways leading to tumorigenesis and the use of PDE inhibitors in colon cancer.
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PMID:Therapeutic opportunities in colon cancer: Focus on phosphodiesterase inhibitors. 3112 64