当前位置： SCI文献检索 > CHEMICAL RESEARCH IN TOXICOLOGY期刊下所有文献 > N-O Reduction and ROS-Mediated AKT/FOXO1 and AKT/P53 Pathways Are Involved in Growth Promotion and Cytotoxicity of Cyadox.

N-O Reduction and ROS-Mediated AKT/FOXO1 and AKT/P53 Pathways Are Involved in Growth Promotion and Cytotoxicity of Cyadox.

Abstract：

:Cyadox is a novel derivative of quinoxaline-1,4-dioxides (QdNOs) with the potential to be developed as a feed additive. However, the pharmacological and toxicological bioactive molecules of cyadox and the molecular mechanism of its pharmacological and toxic actions remain unclear. In the present study, cyadox and its main metabolites of cy1, cy4, cy6, and cy12 were selected; the growth promotion characteristic was indicated by the mRNA level of EGF; and the cytotoxicity of cyadox was determined by methylthiazol tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release, and Annexin V-FITC/PI apoptosis detection kit with flow cytometry. The intracellular ROS, cyclin D1, and Akt/P53/FOXO1 signaling pathway were also investigated. Our data suggested that cyadox showed relatively higher activity than its metabolites, and the ROS was generated from N-O reduction of cyadox. Moreover, cyadox (2 μM) activated the Akt and increased the EGF, cyclin D1, and FOXO1 expression levels. Cyadox (100 μM) induced cytotoxicity in L02 cells in a concentration- and time-dependent manner. Additionally, the activated P53 pathway, hyperactivated Akt, and apoptosis were found in L02 cells after incubation with 100 μM cyadox. Our data demonstrated that Akt promoted cell survival when it was mildly activated by cyadox at 2 μM, and Akt leads to apoptosis when it was severely activated by cyadox at 100 μM. Thus, the present study revealed that N-O reduction of cyadox and ROS-mediated AKT/FOXO1 and AKT/P53 pathways were involved in growth promotion and cytotoxicity of cyadox.

journal_name

Chem Res Toxicol

journal_title

Chemical research in toxicology

authors

Liu Q,Lei Z,Zhou K,Yu H,Liu S,Sun Q,Wang X,Dai M,Yuan Z

doi

10.1021/acs.chemrestox.8b00194

subject

Has Abstract

pub_date

2018-11-19 00:00:00

pages

1219-1229

issue

11

eissn

0893-228X

issn

1520-5010

journal_volume

31

pub_type

杂志文章

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