Identification of Homoharringtonine as a potent inhibitor of glioblastoma cell proliferation and migration.

We previously demonstrated that Annexin A2 (ANXA2) is a pivotal mediator of the pro-oncogenic features displayed by glioblastoma (GBM) tumors, the deadliest adult brain malignancies. In GBM, ANXA2 sustains a transcriptional program involved in cell stemness, proliferation and invasion, negatively impacting patient prognosis. Transcriptional signatures obtained by the modulation of ANXA2 activity/levels were functionally mapped through the QUADrATiC bioinformatic tool for compound identification. Selected compounds were screened by cell proliferation and migration assays in primary GBM cells. Screening of compounds selected through QUADrATiC identified HHT as a potent inhibitor of GBM cell motility and proliferation. A further molecular characterization of the effects displayed by HHT, confirmed its ability to inhibit a transcriptional program involved in cell migration and invasion. Moreover, we demonstrated that the multiple antitumoral effects displayed by HHT are correlated to the inhibition of a PDGFRα-dependent intracellular signaling through the impairment of STAT3 and RhoA axes. Homoharringtonine is a potent inhibitor of GBM cell proliferation and migration Gene expression was measured using Affymetrix platform in primary GBM cells transfected with siNEG or anti-ANXA2 siRNA, and in GBM cells treated or not with homoharringtonine (HHT).