Activation of TAp73 and inhibition of TrxR by Verteporfin for improved cancer therapy in TP53 mutant pancreatic tumors

Future Science OA
Pilar AcedoJoanna Zawacka-Pankau

Abstract

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. 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. 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.

References

Jan 27, 1999·Methods in Enzymology·E S ArnérA Holmgren
Nov 28, 2007·Annual Review of Pathology·Anirban Maitra, Ralph H Hruban
Feb 18, 2009·World Journal of Gastroenterology : WJG·Qi XieCheng-Gang Wei
May 5, 2009·Cancer Cell·Jeremy M R LambertVladimir J N Bykov
May 28, 2011·CA: a Cancer Journal for Clinicians·Patrizia AgostinisJakub Golab
Jun 7, 2011·The New England Journal of Medicine·Paul B ChapmanUNKNOWN BRIM-3 Study Group
Aug 28, 2012·The Journal of Biological Chemistry·Fatbardha VarfajPaul R Ortiz de Montellano
Feb 14, 2013·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M MalvezziE Negri
Oct 24, 2014·Cell Death & Disease·A KosteckaJ Zawacka-Pankau
May 20, 2015·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Igor PuzanovKevin B Kim
Aug 6, 2015·European Journal of Dermatology : EJD·Romain GabeffBrigitte Dreno
Dec 15, 2015·Expert Review of Anticancer Therapy·Ivonne RegelJörg Kleeff
Feb 11, 2016·ACS Chemical Biology·Susan KlaegerBernhard Kuster
Oct 22, 2017·Advances in Cancer Research·Elias S J Arnér
Dec 16, 2017·Nature Reviews. Cancer·Vladimir J N BykovKlas G Wiman
Feb 16, 2018·Science Translational Medicine·William C StaffordElias S J Arnér
Apr 20, 2018·Cell Death & Disease·Qiang ZhangJoanna Zawacka-Pankau

❮ Previous
Next ❯

Methods Mentioned

BETA
FACS
flow cytometry
Fluorescence microscopy

Software Mentioned

GEM
CELLQuest

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.