Akademik Veri Yönetim Sistemi
Cukurova Medical Journal, cilt.48, sa.3, ss.939-947, 2023 (ESCI)
Purpose: Intracellular calcium (Ca2+) signaling plays a role in many cellular events, such as cell proliferation and differentiation, gene transcription, oxidative stress, the antioxidant system, and apoptosis. Transient receptor potential vanilloid 4 (TRPV4) channels are non-selective cation (Ca2+) channels. The present study aims to investigate the cytotoxic activity of RN-1734, a transient receptor potential vanilloid 4 (TRPV4) antagonist, in the G361 human melanoma cancer cell line. Materials and Methods: The effects of RN-1734 on G361 cell viability at concentrations of 1, 5, 25, 50, and 100 μM were measured using the 3-(4,5-dimethylthiazol-2-il)-2,5-diphenyltetrazolium bromide (MTT) method. Total antioxidant status (TAS) and total oxidant status (TOS) levels were determined using a ready-made commercial kit, after which oxidative stress index (OSI) values were calculated. To determine the apoptotic effects of RN-1734, Bcl-2, Bax, and p53 expression levels, caspase-3 and -8 activities were examined via quantitative real-time PCR analysis. Results: G361 cell viability significantly decreased to 82.72, 72.81, 56.36, 39.16 and 18.96% in RN-1734 groups (1, 5, 25, 50 and 100 μM) compared to the control group (100.00%). At IC50 concentration (39.48 μM), RN-1734 application (3.35 mmol/g prot.-TAS, 45.87 μmol/g prot.-TOS, and 1501.97 AU-OSI) increased the TAS level (2.17 mmol/g prot.) and decreased the TOS level (55.41 μmol/g prot.) and OSI value (3142.76 AU) compared to the control group. Conclusion: Our findings show that RN-1734 may be a novel therapeutic approach to treating melanoma by decreasing the cell viability of G361 human melanoma cancer cells.