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RISS 인기검색어
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- 저자 : Francesca Piccione (검색결과 1 건)
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Cristina Vercelli,Raffaella Barbero,Barbara Cuniberti,Silvia Racca,Giuliana Abbadessa,Francesca Piccione,Giovanni Re 한국유방암학회 2014 Journal of breast cancer Vol.17 No.4
Purpose: Transient receptor potential vanilloid 1 (TRPV1) is a nonselectivecation channel belonging to the transient receptor potentialfamily, and it is expressed in different neoplastic tissues. Its activation is associated with regulation of cancer growth andprogression. The aim of this research was to study the expressionand pharmacological characteristics of TRPV1 in cells derivedfrom human breast cancer MCF-7 cells. Methods: TRPV1presence was assessed by binding studies and Western blotting. Receptor binding characteristics were evaluated through competitionassays, while 3-(4,5-dimethylthiazol-2-yl)-2,5,-dipheyltetrazoliumbromide reduction assays were performed to confirman early hypothesis regarding the modulation of cancer cell proliferation. The functionality of TRPV1 was evaluated by measuringCa2+ uptake in the presence of increasing concentrations ofTRPV1 agonists and antagonists. Results: Binding studies identifieda single class of TRPV1 (Bmax 1,492±192 fmol/mg protein),and Western blot showed a signal at 100 kDa corresponding tothe molecular weight of human TRPV1. Among the different testedagonists and antagonists, anandamide (Ki: 2.8×10-11 M) and5-iodoresiniferatoxin (5-I-RTX) (Ki: 5.6×10-11 M) showed the highestdegrees of affinity for TRPV1, respectively. All tested TRPV1agonists and antagonists caused a significant (p<0.05) decreasein cell growth rate in MCF-7 cells. For agonists and antagonists,the efficacy of tested compounds displayed the following rankorder: resiniferatoxin>anandamide>capsaicin and 5-I-RTX=capsazepine, respectively. Conclusion: These data indicate thatboth TRPV1 agonists and antagonists induce significant inhibitionof MCF-7 cell growth. Even though the mechanisms involvedin the antiproliferative effects of TRPV1 agonists and antagonistsshould be further investigated, it has been suggestedthat agonists cause desensitization of the receptor, leading to alterationin Ca2+-influx regulation. By contrast, antagonists causea functional block of the receptor with consequent fatal dysregulationof cell homeostasis.
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