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Title: Exploiting the potential of autophagy in cisplatin therapy: a new strategy to overcome resistance
Author: García-Cano, Jesús
Ambroise, Gorbatchev
Pascual-Serra, Raquel
Carrión, Maria Carmen
Serrano-Oviedo, Leticia
Ortega-Muelas, Marta
Cimas, Francisco J.
Sabater, Sebastià
Ruiz Hidalgo, María José
Sanchez Perez, Isabel
Mas, Antonio
Jalón, Félix A.
Vazquez, Aimé
Sánchez-Prieto, Ricardo
Keywords: Autofàgia
Mort cel·lular
Cell death
Issue Date: 20-Jun-2015
Publisher: Impact Journals
Abstract: Resistance to cisplatin is a major challenge in the current cancer therapy. In order to explore new therapeutic strategies to cisplatin resistance, we evaluated, in a model of lung cancer (H1299 and H460 cell lines), the nature of the pathways leading to cell death. We observed that H1299 displayed a natural resistance to cisplatin due to an inability to trigger an apoptotic response that correlates with the induction of autophagy. However, pharmacological and genetic approaches showed how autophagy was a mechanism associated to cell death rather than to resistance. Indeed, pro-autophagic stimuli such as mTOR or Akt inhibition mediate cell death in both cell lines to a similar extent. We next evaluated the response to a novel platinum compound, monoplatin, able to promote cell death in an exclusive autophagy-dependent manner. In this case, no differences were observed between both cell lines. Furthermore, in response to monoplatin, two molecular hallmarks of cisplatin response (p53 and MAPKs) were not implicated, indicating the ability of this pro-autophagic compound to overcome cisplatin resistance. In summary, our data highlight how induction of autophagy could be used in cisplatin resistant tumours and an alternative treatment for p53 mutated patient in a synthetic lethally approach.
Note: Reproducció del document publicat a:
It is part of: Oncotarget, 2015, vol. 6, num. 17, p. 15551-15565
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ISSN: 1949-2553
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)

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