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*, Demetrius A. Machado de Araújo

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 20 , Issue 17 , 2020


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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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VOLUME: 20
ISSUE: 17
Year: 2020
Page: [2089 - 2098]
Pages: 10
DOI: 10.2174/1871520620666200721124221
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