abstract
1-(1-Naphthyl)piperazine (1-NPZ) is a serotonergic derivative of quipazine acting both as antagonist and agonist of different serotonin receptors, with promising results for the management of skin cancer. In this work, we studied the effect of 1-NPZ on human MNT-1 melanoma cells by evaluating its effects on cell viability, ability to form colonies, cell cycle dynamics, reactive oxygen species (ROS) production and apoptosis. Treatment of MNT-1 cells with 1-NPZ for 24 h decreased cell viability and induced apoptosis in a dose-dependent manner. Activity against melanoma was confirmed with a different melanoma cell line, SK-MEL-28. Simultaneously, 1-NPZ affected cell cycle progression by mediating a S-phase delay. Higher levels of ROS were also detected in MNT-1 cells after treatment with 1-NPZ. Furthermore, 1-NPZ significantly increased the expression of cyclooxygenase-2 in MNT-1 cells. These findings suggest that 1-NPZ pretreatment is able to induce oxidative stress, and consequently apoptotic cell death in melanoma cells. In conclusion, this study demonstrates the cytotoxic and genotoxic potential of 1-NPZ against melanoma cells.
keywords
CIS-UROCANIC ACID; DNA-DAMAGE; IMMUNE SUPPRESSION; CANCER-CELLS; LUNG-CANCER; APOPTOSIS; PHOTOCARCINOGENESIS; RECEPTOR; ASSAY; SKIN
subject category
Toxicology
authors
Menezes, AC; Carvalheiro, M; de Oliveira, JMPF; Ascenso, A; Oliveira, H
our authors
Groups
acknowledgements
The authors acknowledge Dr. Manuela Gaspar (iMed.ULisboa, Portugal) for kindly providing human MNT-1 melanoma cells for this work. Thanks are due, for the financial support to CESAM (UID/AMB/50017), to FCT/MEC through national funds, and the co-funding by the FEDER, within the PT2020 Partnership Agreement and Compete 2020. This work was supported by national funds through the Portuguese Foundation for Science and Technology (FCT) through the fellows of Jose Miguel P. Ferreira de Oliveira (SFRH/BPD/74868/2010) and Helena Oliveira (SFRH/BPD/111736/2015).