Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10899339 | Cancer Letters | 2016 | 10 Pages |
Abstract
We observed that APR-246 synergistically enhanced the cytotoxic response of olaparib in TP53 mutant non-small cell lung cancer cell lines, resulting in a strong apoptotic response. In the presence of wild type p53 a G2/M cell cycle block was predominantly observed. NOXA expression levels were significantly increased in a TP53 mutant background, and remained unchanged in the wild type cell line. The combined treatment of APR-246 and olaparib induced cell death that was associated with increased ROS production, accumulation of DNA damage and translocation of p53 to the mitochondria. Out data suggest a promising targeted combination strategy in which the response to olaparib is synergistically enhanced by the addition of APR-246, especially in a TP53 mutant background.
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Authors
Christophe Deben, Filip Lardon, An Wouters, Ken Op de Beeck, Jolien Van den Bossche, Julie Jacobs, Nele Van Der Steen, Marc Peeters, Christian Rolfo, Vanessa Deschoolmeester, Patrick Pauwels,