Neuroblastoma (NB) is the most common neoplasm during infancy. Unfortunately, NB is still a lethal cancer. Therefore, innovative curative therapies are immediately required. In this study, we showed the prodeath… Click to show full abstract
Neuroblastoma (NB) is the most common neoplasm during infancy. Unfortunately, NB is still a lethal cancer. Therefore, innovative curative therapies are immediately required. In this study, we showed the prodeath activity of TPGS in human NB SK-N-SH cancer cells. NB cells were exposed to TPGS (10-80 μM). We report for the first time that TPGS induces cell death by apoptosis in NB cells via a pro-oxidant-mediated signaling pathway. Certainly, H2O2 directly oxidizes DJ-1 cysteine106-thiolate into DJ-1 cysteine106-sulfonate, indirectly activates the transcription factors NF-kappaB, p53, and c-JUN, induces the upregulation of mitochondria regulator proteins BAX/PUMA, and provokes the loss of mitochondrial membrane potential (ΔΨm) and the activation of caspase-3/AIF, leading to nuclear disintegration, demonstrated by cellular and biochemical techniques such as fluorescence microscopy, flow cytometry, and Western blot analysis. Since TPGS is a U.S. Food and Drug Administration (FDA)-approved pharmaceutical excipient, this molecule might be used in clinical trials for NB treatment.
               
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