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• W4381199585 abstract "Hydroxyapatite nanoparticles (HAPNs) have been reported to specifically induce apoptosis and sustained elevation of intracellular Ca2+ concentration ([Ca2+]i) in cancer cells. However, it remains unclear whether calcium overload, the abnormal intracellular accumulation of Ca2+, is the intrinsic cause of cell apoptosis, how HAPNs specifically evoke calcium overload in cancer cells, and which potential pathways were involved in apoptosis initiation in response to calcium overload. In this study, using various cancer and normal cells, we observed a positive correlation between the degree of increased [Ca2+]i and the specific toxicity of HAPNs. Moreover, chelating intracellular Ca2+ with BAPTA-AM inhibited HAPN-induced calcium overload and apoptosis, thus demonstrating that calcium overload was the main cause of HAPN-induced cytotoxicity in cancer cells. Notably, the dissolution of particles outside the cells did not affect cell viability or [Ca2+]i. In contrast, internalized HAPNs dissolved more readily in cancer cells than in normal cells and inhibited the activity of plasma membrane calcium-ATPase solely in cancer cells to prevent extrusion of excessive Ca2+, hence leading to calcium overload in tumor cells. Upon exposure to HAPNs, the Ca2+-sensitive cysteine protease calpain was activated and then cleaved the BH3-only protein Bid. Consequently, cytochrome c was released, and caspase-9 and -3 were activated, leading to mitochondrial apoptosis. However, these effects were alleviated by the calpain inhibitor calpeptin, confirming the involvement of calpain in HANP-induced apoptosis. Therefore, our results demonstrated that calcium overload induced by HAPNs caused cancer cell-specific apoptosis by inhibiting PMCA and activating calpain in tumor cells and thus may contribute to a more comprehensive understanding of biological effects of this nanomaterial and facilitate the development of calcium overload cancer therapy." @default.
• W4381199585 created "2023-06-20" @default.
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• W4381199585 date "2023-01-01" @default.
• W4381199585 modified "2023-10-16" @default.
• W4381199585 title "Hydroxyapatite nanoparticles induced calcium overload-initiated cancer cell-specific apoptosis through inhibition of PMCA and activation of calpain" @default.
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• W4381199585 doi "https://doi.org/10.1039/d3tb00542a" @default.
• W4381199585 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37403708" @default.
• W4381199585 hasPublicationYear "2023" @default.
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