1. Proapoptotic Effects of triazol-1,4-Naphthoquinones Involve Intracellular ROS Production and MAPK/ERK Pathway in Human Leukemia Cells.
- Author
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Coulidiati TH, Dantas BB, Faheina-Martins GV, de Morais Gomes ER, Gonçalves JCR, and de Araújo DAM
- Subjects
- Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Humans, MAP Kinase Signaling System drug effects, Molecular Structure, Structure-Activity Relationship, Tumor Cells, Cultured, Antineoplastic Agents pharmacology, Apoptosis drug effects, Reactive Oxygen Species metabolism
- Abstract
Background: The natural products constitute an important source of antitumor and cytotoxic agents. Naphthoquinones are effectively quinones present in different plants, with demonstrated anticancer activities. A recent study conducted by our group demonstrated the antileukemic potential of two novel triazol-1,4- naphthoquinones derivatives, PTN (2-(4-Phenyl-1H-1,2,3-triazol-1-yl)-1,4-naphthoquinone) and MPTN (2-[4- (4-Methoxyphenyl)-1H-1,2,3-triazol-1-yl]-1,4-naphthoquinone). Although, the mechanisms underlying the proapoptotic effects of PTN and MPTN have not been fully elucidated so far., Objective: The aim of this study was to evaluate the proapoptotic mechanism of PTN and MPTN in human acute leukemia cells., Methods: We used fluorescence microscopy to observe acridine orange and annexin V staining cells. Flow cytometry assay has also been used for ROS quantification, BAX and cytochrome c proteins expression and apoptosis analysis. MTT assay and western blotting technique have been performed as well for MAPK pathway analysis., Results: By using the acridine orange and annexin V staining with fluorescence microscopy, we have characterized the proapoptotic effects of PTN and MPTN in HL-60 cells involving the intrinsic mitochondrial pathway, since these compounds promoted an increase in the intracellular BAX and cytochrome c protein levels (p<0.05). We further demonstrated that apoptosis induction in HL-60 cells was mediated by increasing intracellular ROS levels via ERK but not p38 MAPKs pathway., Conclusion: Taken together, these results have demonstrated that PTN and MPTN are promising tools for the development of new anti-leukemic drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2020
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