Terfenadine-induced apoptosis in human melanoma cells is mediated through Ca2+ homeostasis modulation and tyrosine kinase activity, independently of H1 histamine receptors
| Autor: | Idoia Ortega-Martínez, Yoana Arroyo-Berdugo, María Dolores Boyano, M. Begoña Ruiz-Larrea, Shawkat-Muhialdin Jangi, J. L. Diaz-Perez, Francesca Nicolau-Galmés, Noelia Andollo |
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| Rok vydání: | 2007 |
| Předmět: |
Histamine H1 Antagonists
Non-Sedating Cancer Research Programmed cell death medicine.medical_specialty Inositol Phosphates Fluorescent Antibody Technique Apoptosis Biology Histamine receptor chemistry.chemical_compound Cell Line Tumor Internal medicine Cyclic AMP medicine Homeostasis Humans Receptors Histamine H1 RNA Small Interfering Cyclic GMP Egtazic Acid Melanoma DNA Primers Base Sequence Phospholipase C Reverse Transcriptase Polymerase Chain Reaction Cell growth General Medicine Protein-Tyrosine Kinases Histamine H1 Antagonists Cell biology Endocrinology chemistry Type C Phospholipases embryonic structures Calcium Electrophoresis Polyacrylamide Gel Terfenadine Tyrosine kinase Histamine Intracellular |
| Zdroj: | Carcinogenesis. 29:500-509 |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/bgm292 |
| Popis: | In our previous works, we have demonstrated that terfenadine (TEF) induces DNA damage and apoptosis in human melanoma cell lines. In this present work, we have studied the effect of histamine on viability of A375 human melanoma cells and the cell-signalling pathways through which TEF may induce its apoptotic effect. We have found that exogenous histamine stimulates A375 melanoma cell proliferation in a dose- and time-dependent manner. Moreover, TEF-induced apoptosis seems to occur via other cellular pathways independent of the histamine-signalling system since co-treatment of histamine with TEF did not protect melanoma cells from the cytotoxic effect of TEF, and alpha fluoromethylhistidine did not induce the same cytotoxic effect of TEF. In addition, we have observed that knocking down the H1 histamine receptor (HRH1) by small interference RNA approach protects melanoma cells only slightly from TEF-induced apoptosis. To explore the molecular mechanisms responsible for histamine and TEF effect on the cell growth, we analysed intracellular cyclic nucleotides and Ca(2+) levels. TEF did not modify intracellular levels of cyclic adenosine 3',5'-monophosphate and cyclic guanine 3',5'-monophosphate; however, TEF induced a very sharp and sustained increase in cytosolic Ca(2+) levels in A375 melanoma cells. On the contrary, histamine did not modulate intracellular Ca(2+). TEF-induced Ca(2+) rise and apoptosis appear to be phospholipase C (PLC) dependent since neomycin and U73122, two inhibitors of PLC, abolished cytosolic Ca(2+) increase and protected the cells completely from cell death. Furthermore, inhibition of tyrosine kinase activity by genistein blocked cytosolic Ca(2+) rise and TEF-induced apoptosis. These results suggest that TEF modulates Ca(2+) homeostasis and induces apoptosis through other cellular pathways involving tyrosine kinase activity, independently of HRH1. |
| Databáze: | OpenAIRE |
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