okadaic-acid and Helicobacter-Infections

The okadaic acid class of tumor promoters, which are inhibitors of protein phosphatases 1 and 2A (PP1 and PP2A), induced tumor promotion in mouse skin, rat glandular stomach, and rat liver. Endogenous protein inhibitors of PP2A, SET and CIP2A, were up-regulated in various human cancers, so it is vital to review the essential mechanisms of tumor promotion by the okadaic acid class compounds, together with cancer progression by SET and CIP2A in humans.. The first part of this review introduces the okadaic acid class compounds and the mechanism of tumor promotion: (1) inhibition of PP1 and PP2A activities of the okadaic acid class compounds; (2) some topics of tumor promotion; (3) TNF-α gene expression as a central mediator in tumor promotion; (4) exposure to the okadaic acid class of tumor promoters in relation to human cancer. The second part emphasizes the overexpression of SET and CIP2A in cancer progression, and the anticancer activity of SET antagonists as follows: (5) isolation and characterization of SET; (6) isolation and characterization of CIP2A; (7) progression of leukemia with SET; (8) progression of breast cancer with SET and CIP2A; (9) progression of lung cancer with SET; (10) anti-carcinogenic effects of SET antagonists OP449 and FTY720; and also (11) TNF-α-inducing protein of Helicobacter pylori, which is a clinical example of the okadaic acid pathway.. The overexpression of endogenous protein inhibitors of PP2A, SET and CIP2A, is tightly linked to the progression of various human cancers, as well as Alzheimer's disease.

Topics: Animals; Autoantigens; Biomarkers, Tumor; Cell Transformation, Neoplastic; Disease Progression; DNA-Binding Proteins; Environmental Exposure; Enzyme Inhibitors; Gene Expression Regulation, Neoplastic; Helicobacter Infections; Helicobacter pylori; Histone Chaperones; Humans; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Molecular Targeted Therapy; Neoplasms; Okadaic Acid; Protein Phosphatase 2; Signal Transduction; Transcription Factors; Tumor Necrosis Factor-alpha

The classic two-stage chemical carcinogenesis in rodents is not directly linked to multistage carcinogenesis in humans. In light of our findings that tumor necrosis factor-α (TNF-α) is an endogenous tumor promoter and that TNF-α-inducing protein (Tipα) of Helicobacter pylori stimulates progression of cancer and epithelial-mesenchymal transition, we think it is necessary to re-examine the concept of tumor promoter, from chemicals to inflammatory proteins.. This paper begins with "inflammation," discovered by Virchow, studies of Yamagiwa and Tsutsui, and briefly reviews numerous topics, such as (1) the classic concept of tumor promoter, (2) tumor promotion on mouse skin induced by protein kinase C activators and okadaic acid class compounds, (3) organ specificity of tumor promoters, presenting numerous tumor promoters in various organs, (4) unique tumor promotion induced by inhibitors of protein phosphatases 1 and 2A in mouse skin, rat glandular stomach, and rat liver, (5) the significant role of TNF-α in tumor-promoting inflammation, (6) progression induced by Tipα of H. pylori, and (7) enhancement of cancer treatment efficacy with the combination of anticancer drugs and green tea catechins, to inhibit tumor-promoting inflammation.. Human cancer development involves both durable genetic changes caused by carcinogens and proinflammatory cytokines, and simultaneous inflammation in progression induced by proinflammatory cytokines and chemokines.

Topics: Animals; Anticarcinogenic Agents; Carcinogens; Catechin; Gastrointestinal Neoplasms; Helicobacter Infections; Humans; Inflammation; Inflammation Mediators; Neoplasms, Experimental; Okadaic Acid; Organ Specificity; Skin Neoplasms