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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Antineoplastic Agents, Apoptosis, Autophagy, Cell Cycle Checkpoints, Cell Line, Tumor, Cell Survival, Humans, Inhibitory Concentration 50, MAP Kinase Signaling System, Membrane Potential, Mitochondrial, Quinuclidines, Reactive Oxygen Species, Sarcoma, Tumor Suppressor Protein p53.
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Does pRIMA-1 ( MET ) induce death in soft-tissue sarcomas cell independent of p53? Context: The aim of this study was to explore the efficacy and define mechanisms of action of PRIMA-1(MET) as a TP53 targeted therapy in soft-tissue sarcoma (STS) cells. We investigated effects of PRIMA-1(MET) on apoptosis, cell cycle, and induction of oxidative stress and autophagy in a panel of 6 STS cell lines with different TP53 status. Cell viability reduction by PRIMA-1(MET) was significantly observed in 5 out of 6 STS cell lines. We found that PRIMA-1(MET) was capable to induce cell death not only in STS cells harboring mutated TP53 but also in TP53-null STS cells demonstrating that PRIMA-1(MET) can induce cell death independently of TP53 in STS cells. We identified an important role of reactive oxygen species (ROS), involved in PRIMA-1(MET) toxicity in STS cells leading to a caspase-independent cell death. ROS toxicity was associated with autophagy induction or JNK pathway activation which represented potential mechanisms of cell death induced by PRIMA-1(MET) in STS.
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PRIMA-1(MET) anti-tumor activity in STS partly results from off-target effects involving ROS toxicity and do not deserve further development as a TP53-targeted therapy in this setting. Final Decision: yes