Acedo, P;
Fernandes, A;
Zawacka-Pankau, J;
(2019)
Activation of TAp73 and inhibition of TrxR by Verteporfin for improved cancer therapy in TP53 mutant pancreatic tumors.
Future Science
, 5
(2)
, Article FSO366. 10.4155/fsoa-2018-0082.
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Abstract
Aim: TAp73 is a tumor suppressor, which compensates for p53 loss and induces apoptosis in tumors in response to genotoxic stress or small-molecule treatments. Pancreatic ductal adenocarcinoma has a late onset of the disease, responds poorly to the existing therapies and has a very low survival rates. Result: Here, using drug-repurposing approach, we found that protoporphyrin IX (PpIX) and benzoporphyrin derivative (BPD) monoacid ring A activate TAp73 and induce apoptosis in pancreatic cancer cells. PpIX and BPD induce reactive oxygen species and inhibit thioredoxin reductase 1. Conclusion: Thus, PpIX and BPD target cancer cells' vulnerabilities namely activate TAp73 tumor suppressor and inhibit oncogenic Trx1. Our findings may contribute to faster repurposing of PpIX and BPD to treat pancreatic tumors.
| Type: | Article |
|---|---|
| Title: | Activation of TAp73 and inhibition of TrxR by Verteporfin for improved cancer therapy in TP53 mutant pancreatic tumors |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.4155/fsoa-2018-0082 |
| Publisher version: | http://doi.org/10.4155/fsoa-2018-0082 |
| Language: | English |
| Additional information: | Copyright © Authors 2019, Open access This work is licensed under the Creative Commons Attribution4.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | ROS, TAp73, apoptosis, benzoporphyrin derivative, drug repurposing, mutant p53, pancreatic cancer, protoporphyrin IX, thioredoxin reductase |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10072001 |
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