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.
Highlights
Dual targeting of TAp73 and TrxR by small molecules that we have identified might bring therapeutic advantage in overcoming the development of the treatment-resistant disease
The authors would like to thank all of their colleagues for sharing their reagents
Here we speculated that PpIX, exogenously delivered to pancreatic cancer cells harboring TP53 mutations, will induce apoptosis via activation of future science group www.future-science.com
Summary
TAp73 is a tumor suppressor, which compensates for p53 loss and induces apoptosis in tumors in response to genotoxic stress or small-molecule treatments
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