Transient Receptor Potential Vanilloid 1 Expression and Functionality in MCF-7 Cells: A Preliminary Investigation
Autor: | Giuliana Abbadessa, Silvia Racca, Francesca Piccione, Giovanni Re, Cristina Vercelli, Raffaella Barbero, B. Cuniberti |
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Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Cancer Research
Cell growth business.industry Functionality assays TRPV1 Competition assays Anandamide Pharmacology TRPV1 receptor TRPC5 Blot chemistry.chemical_compound Oncology chemistry 3-(4 5-dimethylthiazol-2-yl)-2 5-diphenyl tetrazolium bromide Medicine lipids (amino acids peptides and proteins) TRPM2 Original Article MCF-7 cells Receptor business Capsazepine |
Zdroj: | Journal of Breast Cancer |
ISSN: | 2092-9900 1738-6756 |
Popis: | Purpose Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel belonging to the transient receptor potential family, and it is expressed in different neoplastic tissues. Its activation is associated with regulation of cancer growth and progression. The aim of this research was to study the expression and pharmacological characteristics of TRPV1 in cells derived from human breast cancer MCF-7 cells. Methods TRPV1 presence was assessed by binding studies and Western blotting. Receptor binding characteristics were evaluated through competition assays, while 3-(4,5-dimethylthiazol-2-yl)-2,5,-dipheyltetrazolium bromide reduction assays were performed to confirm an early hypothesis regarding the modulation of cancer cell proliferation. The functionality of TRPV1 was evaluated by measuring Ca2+ uptake in the presence of increasing concentrations of TRPV1 agonists and antagonists. Results Binding studies identified a single class of TRPV1 (Bmax 1,492±192 fmol/mg protein), and Western blot showed a signal at 100 kDa corresponding to the molecular weight of human TRPV1. Among the different tested agonists and antagonists, anandamide (Ki: 2.8×10-11 M) and 5-iodoresiniferatoxin (5-I-RTX) (Ki: 5.6×10-11 M) showed the highest degrees of affinity for TRPV1, respectively. All tested TRPV1 agonists and antagonists caused a significant (panandamide>capsaicin and 5-I-RTX=capsazepine, respectively. Conclusion These data indicate that both TRPV1 agonists and antagonists induce significant inhibition of MCF-7 cell growth. Even though the mechanisms involved in the antiproliferative effects of TRPV1 agonists and antagonists should be further investigated, it has been suggested that agonists cause desensitization of the receptor, leading to alteration in Ca2+-influx regulation. By contrast, antagonists cause a functional block of the receptor with consequent fatal dysregulation of cell homeostasis. |
Databáze: | OpenAIRE |
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