Titania nanosheet generates peroxynitrite-dependent S-nitrosylation and enhances p53 function in lung cancer cells

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dc.contributor.authorSoonnarong, Rapeepun
dc.contributor.authorTungsukruthai, Sucharat
dc.contributor.authorNutho, Bodee
dc.contributor.authorRungrotmongkol, Thanyada
dc.contributor.authorVinayanuwattikun, Chanida
dc.contributor.authorMaluangnont, Tosapol
dc.contributor.authorChanvorachote, Pithi
dc.date.accessioned2026-08-06T10:33:12Z
dc.date.available2026-08-06T10:33:12Z
dc.date.issued2021-08-01
dc.description.abstractMetal nanomaterials can enhance the efficacy of current cancer therapies. Here, we show that Ti<inf>0.8</inf> O<inf>2</inf> nanosheets cause cytotoxicity in several lung cancer cells but not in normal cells. The nanosheet-treated cells showed certain apoptosis characteristics. Protein analysis further indicated the activation of the p53-dependent death mechanism. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses revealed the cellular uptake of the nanosheets and the induction of cell morphological change. The nanosheets also exhibited a substantial apoptosis effect on drug-resistant metastatic primary lung cancer cells, and it was found that the potency of the nanosheets was dramatically higher than standard drugs. Ti<inf>0.8</inf> O<inf>2</inf> nanosheets induce apoptosis through a molecular mechanism involving peroxynitrite (ONOO<sup>−</sup>) generation. As peroxynitrite is known to be a potent inducer of S-nitrosylation, we further found that the nanosheets mediated the S-nitrosylation of p53 at C182, resulting in higher protein-protein complex stability, and this was likely to induce the surrounding residues, located in the interface region, to bind more strongly to each other. Molecular dynamics analysis revealed that S-nitrosylation stabilized the p53 dimer with a ∆Gbind<sup>residue</sup> of <−1.5 kcal/mol. These results provide novel insight on the apoptosis induction effect of the nanosheets via a molecular mechanism involving S-nitrosylation of the p53 protein, emphasizing the mechanism of action of nanomaterials for cancer therapy.
dc.identifier.citationPharmaceutics, 13(8), 2021
dc.identifier.doi10.3390/pharmaceutics13081233
dc.identifier.issn19994923
dc.identifier.other2-s2.0-85112745989
dc.identifier.urihttps://dspace.kmitl.ac.th/handle/123456789/12197
dc.sourcePharmaceutics
dc.subjectApoptosis
dc.subjectLung cancer
dc.subjectMolecular dynamics
dc.subjectNanosheets
dc.subjectP53
dc.subjectPeroxynitrite
dc.subjectS-nitrosylation
dc.titleTitania nanosheet generates peroxynitrite-dependent S-nitrosylation and enhances p53 function in lung cancer cells
dc.typeArticle

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