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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Proapoptotic Effects of triazol-1,4-Naphthoquinones Involve Intracellular ROS Production and MAPK/ERK Pathway in Human Leukemia Cells

Author(s): Tangbadioa H. Coulidiati, Bruna B. Dantas, Glaucia V. Faheina-Martins, Enéas Ricardo de Morais Gomes, Juan C.R. Gonçalves* and Demetrius A. Machado de Araújo

Volume 20, Issue 17, 2020

Page: [2089 - 2098] Pages: 10

DOI: 10.2174/1871520620666200721124221

Price: $65

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.

Keywords: Cancer, acute leukemia, naphthoquinone, cytotoxicity, HL-60, reactive oxygen species.

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