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Background  The primary glioblastoma multiforme (GBM) is the most malignant form of astrocytic tumor with an average survival of approximately 12–14 months. The search for novel and more efficient chemo-agents against this disease is urgent. Salinomycin induces broad anti-cancer effects; however, its role in GBM and the underlying mechanism are not clear.    Results  Here we found that salinomycin induced both apoptosis and necrosis in cultured glioma cells, and necrosis played a major role in contributing salinomycin’s cytotoxicity. Salinomycin induced p53 translocation to mitochondria, where it formed a complex with cyclophilin-D (CyPD). This complexation was required for mitochondrial permeability transition pore (mPTP) opening and subsequent programmed necrosis. Blockade of Cyp-D by siRNA-mediated depletion or pharmacological inhibitors (cyclosporin A and sanglifehrin A) significantly suppressed salinomycin-induced glioma cell necrosis. Meanwhile, p53 stable knockdown alleviated salinomycin-induced necrosis in glioma cells. Reactive oxygen species (ROS) production was required for salinomycin-induced p53 mitochondrial translocation, mPTP opening and necrosis, and anti-oxidants n-acetylcysteine (NAC) and pyrrolidine dithiocarbamate (PDTC) inhibited p53 translocation, mPTP opening and glioma cell death.    Conclusions  Thus, salinomycin mainly induces programmed necrosis in cultured glioma cells.    Electronic supplementary material  The online version of this article (doi:10.1186/s13046-015-0174-1) contains supplementary material, which is available to authorized users.

ROS-p53-cyclophilin-D signaling mediates salinomycin-induced glioma cell necrosis