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Sci Rep. 2014 Apr 23;4:4749. doi: 10.1038/srep04749.

Apoptosis therapy in cancer: the first single-molecule co-activating p53 and the translocator protein in glioblastoma.

Author information

1
Department of Pharmacy, University of Pisa, Pisa, Italy.
2
Department of Clinical and Experimental Medicine, University of Pisa, Italy.
3
Department of Pharmacy, University of Naples Federico II, Italy.
4
Dipartimento di Scienze Motorie, University of Naples "Parthenope", Naples, Italy.

Abstract

In the complex scenario of cancer, treatment with compounds targeting multiple cell pathways has been emerging. In Glioblastoma Multiforme (GBM), p53 and Translocator Protein (TSPO), both acting as apoptosis inducers, represent two attractive intracellular targets. On this basis, novel indolylglyoxylyldipeptides, rationally designed to activate TSPO and p53, were synthesized and biologically characterized. The new compounds were able to bind TSPO and to reactivate p53 functionality, through the dissociation from its physiological inhibitor, murine double minute 2 (MDM2). In GBM cells, the new molecules caused Δψm dissipation and inhibition of cell viability. These effects resulted significantly higher with respect to those elicited by the single target reference standards applied alone, and coherent with the synergism resulting from the simultaneous activation of TSPO and p53. Taken together, these results suggest that TSPO/MDM2 dual-target ligands could represent a new attractive multi-modal opportunity for anti-cancer strategy in GBM.

PMID:
24756113
PMCID:
PMC3996484
DOI:
10.1038/srep04749
[Indexed for MEDLINE]
Free PMC Article

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