Targeting breast cancer cells by MRS1477, a positive allosteric modulator of TRPV1 channels
Yazarlar (11)
Mustafa Naziroǧlu
Süleyman Demirel Üniversitesi, Türkiye
Doç. Dr. Bilal ÇİĞ
Süleyman Demirel Üniversitesi, Türkiye
Walter Blum
University Of Fribourg, İsviçre
Csaba Vizler
Hun-Ren Biological Research Centre, Szeged, Macaristan
Andrea Buhala
Hun-Ren Biological Research Centre, Szeged, Macaristan
Annamária Marton
Hun-Ren Biological Research Centre, Szeged, Macaristan
Róbert Katona
Hun-Ren Biological Research Centre, Szeged, Macaristan
Katalin Jósvay
Hun-Ren Biological Research Centre, Szeged, Macaristan
Beat Schwaller
University Of Fribourg, İsviçre
Zoltán Oláh
Miskolci Egyetem, Macaristan
László Pecze
University Of Fribourg, İsviçre
| Makale Türü |
Özgün Makale
(SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale)
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| Dergi Adı | Plos One | ||
| Dergi ISSN | 1932-6203 Wos Dergi Scopus Dergi | ||
| Dergi Tarandığı Indeksler | SCI | ||
| Makale Dili | İngilizce | Basım Tarihi | 06-2017 |
| Cilt / Sayı / Sayfa | 12 / 6 / 179950–0 | DOI | 10.1371/journal.pone.0179950 |
| Makale Linki | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0179950&type=printable | ||
| Özet |
| There is convincing epidemiological and experimental evidence that capsaicin, a potent natural transient receptor potential cation channel vanilloid member 1 (TRPV1) agonist, has anticancer activity. However, capsaicin cannot be given systemically in large doses, because of its induction of acute pain and neurological inflammation. MRS1477, a dihydropyridine derivative acts as a positive allosteric modulator of TRPV1, if added together with capsaicin, but is ineffective, if given alone. Addition of MRS1477 evoked Ca2+ signals in MCF7 breast cancer cells, but not in primary breast epithelial cells. This indicates that MCF7 cells not only express functional TRPV1 channels, but also produce endogenous TRPV1 agonists. We investigated the effects of MRS1477 and capsaicin on cell viability, caspase-3 and -9 activities and reactive oxygen species production in MCF7 cells. The fraction of apoptotic cells was increased after 3 days incubation with capsaicin (10 mu M) paralleled by increased reactive oxygen species production and caspase activity. These effects were even more pronounced, when cells were incubated with MRS1477 (2 mu M) either alone or together with CAPS (10 mu M). Capsazepine, a TRPV1 blocker, inhibited both the effect of capsaicin and MRS1477. Whole-cell patch clamp recordings revealed that capsaicinevoked TRPV1-mediated current density levels were increased after 3 days incubation with MRS1477 (2 mu M). However, the tumor growth in MCF7 tumor-bearing immunodeficient mice was not significantly decreased after treatment with MRS1477 (10 mg/kg body weight, i.p., injection twice a week). In conclusion, in view of a putative in vivo treatment with MRS1477 or similar compounds further optimization is required. |
| Anahtar Kelimeler |
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| WoS | 29 |
| SCOPUS | 32 |