title: The citrus methoxyflavone tangeretin affects human cell-cell interactions.
abstract: Two effects of the citrus methoxyflavone tangeretin on cell-cell interactions are biologically relevant. Firstly, tangeretin upregulates the function of the E-cadherin/catenin complex in human MCF-7/6 breast carcinoma cells. This leads to firm cell-cell adhesion and inhibition of invasion in vitro. Secondly, tangeretin downregulates the interleukin-2 receptor on T-lymphocytes and natural killer cells. This leads to a decrease in the cytotoxic competence of these immunocytes against cancer cells. The second effect can become important when high doses of tangeretin are combined with adjuvant tamoxifen treatment for breast cancer. Experiments with nude mice bearing MCF-7/6 tumors showed that tangeretin given orally at high doses, abrogated the therapeutic suppression of tumor growth exerted by tamoxifen. No evidence for a tumor promoting effect of tangeretin by itself was found in these experiments. Tangeretin may be an interesting molecule for application in cases where immunosuppression could be clinically beneficial.
authors.affiliation: Department of Radiotherapy, Nuclear Medicine and Experimental Cancerology, Ghent University Hospital, Gent, Belgium. brackemarc@hotmail.com
authors.forename: Marc E
authors.initials: ME
authors.lastname: Brack
authors.forename: Tom
authors.initials: T
authors.lastname: Boterberg
authors.forename: Herman T
authors.initials: HT
authors.lastname: Depypere
authors.forename: Christophe
authors.initials: C
authors.lastname: Stove
authors.forename: Georges
authors.initials: G
authors.lastname: Leclercq
authors.forename: Marc M
authors.initials: MM
authors.lastname: Mareel
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology; D015820:Cadherins / Q000502:physiology; D002277:Carcinoma / Q000276:immunology / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects*; D002957:Citrus / Q000737:chemistry*; D000075202:Contraindications; D003598:Cytoskeletal Proteins / Q000502:physiology; D004347:Drug Interactions; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D005260:Female; D047309:Flavones; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000633:toxicity; D007694:Killer Cells, Natural / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000502:physiology; D013629:Tamoxifen / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015534:Trans-Activators / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D015820:Cadherins; D003598:Cytoskeletal Proteins; D020847:Estrogen Receptor Modulators; D047309:Flavones; D005419:Flavonoids; D007166:Immunosuppressive Agents; D009363:Neoplasm Proteins; D015534:Trans-Activators; D051176:beta Catenin; D013629:Tamoxifen; C059006:tangeretin