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Targeting breast cancer cells by MRS1477, a positive allosteric modulator of TRPV1 channels

  • Nazıroğlu, Mustafa Neuroscience Research Center, Suleyman Demirel University, Isparta, Turkey - Department of Neuroscience, Health Science Institute, Suleyman Demirel University, Isparta, Turkey
  • Çiğ, Bilal Department of Neuroscience, Health Science Institute, Suleyman Demirel University, Isparta, Turkey
  • Blum, Walter Unit of Anatomy, Department of Medicine, University of Fribourg, Switzerland
  • Vizler, Csaba Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary
  • Buhala, Andrea Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary
  • Marton, Annamária Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary
  • Katona, Róbert Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary
  • Jósvay, Katalin Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary
  • Schwaller, Beat Unit of Anatomy, Department of Medicine, University of Fribourg, Switzerland
  • Oláh, Zoltán Institute of Chemistry, Faculty, of Materials Science and Engineering, University of Miskolc, Miskolc-Egyetemva Âros, Hungary - Acheuron Ltd., Szeged, Hungary
  • Pecze, László Unit of Anatomy, Department of Medicine, University of Fribourg, Switzerland
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    22.06.2017
Published in:
  • PLOS ONE. - 2017, vol. 12, no. 6, p. e0179950
English 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 μM) paralleled by increased reactive oxygen species production and caspase activity. These effects were even more pronounced, when cells were incubated with MRS1477 (2 μM) either alone or together with CAPS (10 μM). Capsazepine, a TRPV1 blocker, inhibited both the effect of capsaicin and MRS1477. Whole-cell patch clamp recordings revealed that capsaicin-evoked TRPV1-mediated current density levels were increased after 3 days incubation with MRS1477 (2 μM). 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.
Faculty
Faculté des sciences et de médecine
Department
Département de Médecine
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/305888
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