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Cytotoxic activity of gallic acid and myricetin against ovarian cancer cells by production of reactive oxygen species.
* 1 , 2 , 3 , 2 , 1
1  Faculty of Nursing and Nutriology, Autonomous University of Chihuahua
2  Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies
3  Faculty of Chemical Sciences, Autonomous University of Chihuahua

Abstract:

Some studies demonstrate that gallic acid (GA) and myricetin (MYR) isolated from Rhus trilobata provide the therapeutic activity of the plant against cancer. However, few reports demonstrate that both compounds also could have therapeutic potential in ovarian cancer treatment. Therefore, to evaluate the cytotoxic activity of GA and MYR against ovarian cancer cells and to determine the possible action mechanism present is important. With this purpose, SKOV-3 ovarian adenocarcinoma cells (HTB-77™, ATCC®) were cultivated at 37°C with 5% CO2 according to supplier's instructions for determine the biological activity of GA and MYR by confocal/transmission electron microscopy, PI-flow cytometry, H2DCF-DA, MTT and Annexin V/PI assays. Possible molecular targets of the compounds were determined by Similarity Ensemble Approach model. Results showed that GA and Myr treatments decreased viability of SKOV-3 cells at 50 and 166 μg/mL respectively (p ≤ 0.05, ANOVA vs vehicle group); As well as morphological changed (cytoplasmatic reduction, nuclear chromatin condensation, cytoplasmic vesicles increment, polymerized actin, and stabilized tubulin), cell cycle arrest (GA: 8.3% G2/M and MYR: 78% G1), and apoptosis induction (GA: 18.9% and MYR: 8.1%), because to ROS generation (34 to 42%) for 24 h (p ≤ 0.05, ANOVA vs vehicle group). In silico studies demonstrated that GA and MYR interact with carbonic anhydrase and PI3K, respectively. As conclusions, GA and MYR show cytotoxic activity against SKOV-3 cells through ROS production, which modify the cytoskeleton and induce apoptosis mainly. Therefore, GA and Myr could be considered as a starting point for the development of novel anticancer agents.

Keywords: Gallic acid; Myricetin; Cytotoxic activity; SKOV-3; Reactive oxygen species
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