Activation of TAp73 and Inhibition of TrxR by Verteporfin for Improved Cancer Therapy in TP53 Mutant Pancreatic Tumors | Zendy

Pilar Acedo | Zendy; Aristi P. Fernandes | Zendy; Joanna ZawackaPankau | Zendy

Open Access

Activation of TAp73 and Inhibition of TrxR by Verteporfin for Improved Cancer Therapy in TP53 Mutant Pancreatic Tumors

Author(s) -

Pilar Acedo,

Aristi P. Fernandes,

Joanna ZawackaPankau

Publication year - 2019

Publication title -

future science oa

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.825

H-Index - 23

ISSN - 2056-5623

DOI - 10.4155/fsoa-2018-0082

Subject(s) - pancreatic cancer , cancer research , mutant , gemcitabine , verteporfin , cancer , medicine , biology , genetics , surgery , visual acuity , choroidal neovascularization , gene

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.

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