| dc.description.abstract | Neuroblastoma (NB) is a neural cancer originating from embryonic neural crest cells of the sympathetic nervous system. It represents the most prevalent extracranial solid tumor in children, and patients classified as high-risk typically face a poor prognosis with low survival rates. Developing an effective anti-tumor drug for high-risk patients is urgent for the current NB treatment. Selenocystine (SeC), a selenium-containing amino acid, has emerged as a promising candidate for anti-tumor therapy in several previous studies. Importantly, SeC can selectively target cancer cells while sparing normal cells from harm. Despite the documented anti-proliferative effects and the advantageous characteristic of SeC across various cancer types, its therapeutic potential in NB remains largely unexplored. In this study, we aim to investigate the efficacy of SeC as a therapeutic agent for NB using SK-N-BE(2)C and SK-N-SH cells as in-vitro models. Cell counting, MTS assays, and colony formation assays revealed a dose-dependent reduction in cell viability following SeC treatment, underscoring its anti-proliferative effects in NB. Further analysis using flow cytometry demonstrated SeC-induced accumulation of cells in the sub-G1 phase and an increase in Annexin V-positive cells, indicative of apoptosis. Regardless of the protein markers of apoptosis such as PARP, Caspase 3, Caspase 8, and Bcl-2, or the mRNAs expression levels of apoptosis-related genes such as Bcl-2 and Bax, both of them showed significant apoptosis induced by SeC. To elucidate the underlying mechanisms, RNA-Seq analysis was employed in SeC-treated SK-N-BE(2)C cells. From the over-representation analysis of Biological Process (BP) and Disease Ontology (DO), it is evident that numerous genes related to neural functions are altered. This further confirms that SeC has a huge impact on NB cells. The volcano plot revealed significant upregulation of the KLF4 and CDKN1A genes, indicating that SeC-induced cell cycle arrest and apoptosis in NB cells may be mediated by the KLF4-CDKN1A pathway. Subsequent studies will explore the specific roles of KLF4 and CDKN1A in SeC-induced responses in NB cells. Additionally, an in-vivo xenograft study will be conducted to validate the therapeutic potential of SeC in a more physiological setting. | en_US |