| First Author | Shchors K | Year | 2015 |
| Journal | Cancer Cell | Volume | 28 |
| Issue | 4 | Pages | 456-471 |
| PubMed ID | 26412325 | Mgi Jnum | J:225946 |
| Mgi Id | MGI:5695376 | Doi | 10.1016/j.ccell.2015.08.012 |
| Citation | Shchors K, et al. (2015) Dual Targeting of the Autophagic Regulatory Circuitry in Gliomas with Repurposed Drugs Elicits Cell-Lethal Autophagy and Therapeutic Benefit. Cancer Cell 28(4):456-71 |
| abstractText | The associations of tricyclic antidepressants (TCAs) with reduced incidence of gliomas and elevated autophagy in glioma cells motivated investigation in mouse models of gliomagenesis. First, we established that imipramine, a TCA, increased autophagy and conveyed modest therapeutic benefit in tumor-bearing animals. Then we screened clinically approved agents suggested to affect autophagy for their ability to enhance imipramine-induced autophagy-associated cell death. The anticoagulant ticlopidine, which inhibits the purinergic receptor P2Y12, potentiated imipramine, elevating cAMP, a modulator of autophagy, reducing cell viability in culture, and increasing survival in glioma-bearing mice. Efficacy of the combination was obviated by knockdown of the autophagic regulatory gene ATG7, implicating cell-lethal autophagy. This seemingly innocuous combination of TCAs and P2Y12 inhibitors may have applicability for treating glioma. |
