The citrus methoxyflavone tangeretin affects human cell-cell interactions.
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.
Brack
Marc E
ME
Department of Radiotherapy, Nuclear Medicine and Experimental Cancerology, Ghent University Hospital, Gent, Belgium. brackemarc@hotmail.com
Boterberg
Tom
T
Depypere
Herman T
HT
Stove
Christophe
C
Leclercq
Georges
G
Mareel
Marc M
MM
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
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