Genistein reduces proliferation of EP3-expressing melanoma cells through inhibition of PGE2-induced IL-8 expression
| Autor: | Diana Teti, Rosaria Oteri, Isabella Venza, Concetta Beninati, Maria Visalli, Mario Venza |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Angiogenesis Immunology Genistein Genistein Melanoma IL-8 PGE2 EP receptors Dinoprostone 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Tumor Cells Cultured medicine Anticarcinogenic Agents Humans Immunology and Allergy Receptor Melanoma Cell Proliferation Pharmacology Dose-Response Relationship Drug Chemistry Cell growth Interleukin-8 Cell cycle medicine.disease Antineoplastic Agents Phytogenic 030104 developmental biology 030220 oncology & carcinogenesis Receptors Prostaglandin E EP3 Subtype Cutaneous melanoma Cancer research Female |
| Popis: | Genistein, a natural isoflavone found in soybean products, is considered as a powerful anti-cancer agent, although the involved mechanisms are not fully understood. There is a growing body of evidence that, among the genes inhibited by genistein and responsible for cell cycle progression, invasion, metastasis, and angiogenesis, IL-8 occupies a relevant place. On the other hand, it is equally well documented that IL-8 is upregulated by prostaglandin E2 (PGE2) in different pathological conditions, particularly in neoplastic disease. Here we investigated whether genistein could affect cell growth in a panel of oral, uveal and cutaneous melanoma cell lines by interfering with basal or PGE2-induced IL-8 production. To this end, experiments were performed to evaluate the effect of PGE2 treatment on IL-8 levels, the expression and the role of PGE2 receptors and whether genistein could be able to interfere with these events. Finally, it was evaluated whether the inhibition of oral, uveal and cutaneous melanoma cell proliferation in the presence of genistein could be related to a reduction of IL-8 levels. We show that PGE2 enhances IL-8 synthesis via the EP3 receptor and that genistein is able to down-regulate the latter, as well as to decrease IL-8 mRNA and protein expression, thereby inhibiting oral, uveal and cutaneous melanoma cell proliferation. Taken together, our data provide new insights into the anti-cancer properties of genistein by showing that this flavonoid may affect the development and growth of melanoma at oral, uveal and cutaneous sites. Moreover, these results provide evidence that genistein may exert its therapeutic activity through its ability to prevent PGE2-mediated IL-8 induction. |
| Databáze: | OpenAIRE |
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