p53-Mediated PI3KAKTmTOR Pathway Played a Role in PtoxDpt-Induced EMT Inhibition in Liver Cancer Cell Lines
Joint Authors
Fu, Yun
Li, Changzheng
Li, Yongli
Wang, Tingting
Sun, Yanjie
Huang, Tengfei
Li, Cuiping
Li, Yichun
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-05-05
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
Epithelial-mesenchymal transition (EMT) involves metastasis and drug resistance; thus, a new EMT reversing agent is required.
It has shown that wild-type p53 can reverse EMT back to epithelial characteristics, and iron chelator acting as a p53 inducer has been demonstrated.
Moreover, recent study revealed that etoposide could also inhibit EMT.
Therefore, combination of etoposide with iron chelator might achieve better inhibition of EMT.
To this end, we prepared di-2-pyridineketone hydrazone dithiocarbamate S-propionate podophyllotoxin ester (PtoxDpt) that combined the podophyllotoxin (Ptox) structural unit (etoposide) with the dithiocarbamate unit (iron chelator) through the hybridization strategy.
The resulting PtoxDpt inherited characteristics from parent structural units, acting as both the p53 inducer and topoisomerase II inhibitor.
In addition, the PtoxDpt exhibited significant inhibition in migration and invasion, which correlated with downregulation of matrix metalloproteinase (MMP).
More importantly, PtoxDpt could inhibit EMT in the absence or presence of TGF-β1, concomitant to the ROS production, and the additional evidence revealed that PtoxDpt downregulated AKT/mTOR through upregulation of p53, indicating that PtoxDpt induced EMT inhibition through the p53/PI3K/AKT/mTOR pathway.
American Psychological Association (APA)
Li, Yongli& Wang, Tingting& Sun, Yanjie& Huang, Tengfei& Li, Cuiping& Fu, Yun…[et al.]. 2019. p53-Mediated PI3KAKTmTOR Pathway Played a Role in PtoxDpt-Induced EMT Inhibition in Liver Cancer Cell Lines. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1202749
Modern Language Association (MLA)
Li, Yongli…[et al.]. p53-Mediated PI3KAKTmTOR Pathway Played a Role in PtoxDpt-Induced EMT Inhibition in Liver Cancer Cell Lines. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-15.
https://search.emarefa.net/detail/BIM-1202749
American Medical Association (AMA)
Li, Yongli& Wang, Tingting& Sun, Yanjie& Huang, Tengfei& Li, Cuiping& Fu, Yun…[et al.]. p53-Mediated PI3KAKTmTOR Pathway Played a Role in PtoxDpt-Induced EMT Inhibition in Liver Cancer Cell Lines. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1202749
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1202749