Ti0.8O2 nanosheets inhibit lung cancer stem cells by inducing production of superoxide anion

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dc.contributor.authorPetpiroon, Nalinrat
dc.contributor.authorBhummaphan, Narumol
dc.contributor.authorSoonnarong, Rapeepun
dc.contributor.authorChantarawong, Wipa
dc.contributor.authorMaluangnont, Tosapol
dc.contributor.authorPongrakhananon, Varisa
dc.contributor.authorChanvorachote, Pithi
dc.date.accessioned2026-08-06T10:24:24Z
dc.date.available2026-08-06T10:24:24Z
dc.date.issued2019-04-01
dc.description.abstractRecent research into the cancer stem cell (CSC) concept has driven progress in the understanding of cancer biology and has revealed promising CSC-specific targets for drug discovery efforts. As malignancies of lung cancer have been shown to be strongly associated with activities of CSCs, we examined the effects of Ti<inf>0.8</inf>O<inf>2</inf> nanosheets on these cells. Here we show that the nanosheets target lung CSCs but not normal primary dermal papilla (DP) stem cells. Whereas Ti<inf>0.8</inf>O<inf>2</inf> caused a dramatic apoptosis along with a decrease in CSC phenotypes, in primary human DP cells such effects of nanosheets have been minimal. Nanosheets reduced the ability of lung cancer cells to generate three-dimensional tumor spheroids, lung CSC markers (CD133 and ALDH1A1), and CSC transcription factors (Nanog and Oct-4). Ti<inf>0.8</inf>O<inf>2</inf> nanosheets reduced CSC signaling through mechanisms involving suppression of protein kinase B (AKT) and Notch-1 pathways. In addition, the nanosheets inhibited the migration and invasive activities of lung cancer cells and reduced epithelial-to-mesenchymal transition (EMT) markers as N-cadherin, vimentin, and Slug, as well as metastasis-related integrins (integrin-av and integrin-b1). Importantly, we found that the selectivity of the Ti<inf>0.8</inf>O<inf>2</inf> nanosheets in targeting cancer cells was mediated by induction of cellular superoxide anion in cancerous but not normal cells. Inhibition of nanosheet-induced superoxide anion restored the suppression of CSC and EMT in cancer cells. These findings demonstrate a promising distinctive effect of Ti<inf>0.8</inf>O<inf>2</inf> nanosheets on lung CSC that may lead to opportunities to use such a nanomaterial in cancer therapy.
dc.identifier.citationMolecular Pharmacology, 95(4), 418-432, 2019
dc.identifier.doi10.1124/mol.118.114447
dc.identifier.issn0026895X
dc.identifier.other2-s2.0-85062602763
dc.identifier.urihttps://dspace.kmitl.ac.th/handle/123456789/9807
dc.sourceMolecular Pharmacology
dc.titleTi0.8O2 nanosheets inhibit lung cancer stem cells by inducing production of superoxide anion
dc.typeArticle

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