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This study investigated the anticancer effects of the exogenous hydrogen sulfide (H\u2082S) donor, sodium hydrogen sulfide (NaHS), on neuroblastoma cells, elucidating how it inhibits cell proliferation. The study was conducted using the SH-SY5Y cell line. The cells were exposed to various concentrations of NaHS (32, 16, 8, 4, and 2 mM) for 24 h. Cell viability was assessed using the XTT assay. ELISA was used to measure levels of the growth signal factors HER-2, EGFR, mTOR, ERK-1, and ERK-2, as well as the apoptosis marker caspase-3. In addition, apoptosis was evaluated using the Muse Annexin V &amp; Dead Cell Assay Kit. NaHS significantly reduced cell proliferation, as demonstrated by the XTT assay (<jats:italic>p <\/jats:italic>&lt; 0.001). NaHS treatment also decreased levels of HER-2, EGFR, ERK-1, and ERK-2 (<jats:italic>p <\/jats:italic>&lt; 0.05 to <jats:italic>p <\/jats:italic>&lt; 0.01), while mTOR levels remained unchanged (<jats:italic>p <\/jats:italic>&gt; 0.05) and caspase-3 levels increased (<jats:italic>p <\/jats:italic>&lt; 0.001). Flow cytometry confirmed that NaHS treatment significantly increased the proportion of apoptotic cells (<jats:italic>p <\/jats:italic>&lt; 0.001). The antiproliferative effect of NaHS against neuroblastoma appears to be mediated through the suppression of certain growth signal factors and the induction of apoptosis. These findings suggest that exogenous hydrogen sulfide donors hold promise as a potential therapeutic strategy for neuroblastoma.<\/jats:p>","DOI":"10.1007\/s12032-025-02772-8","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T08:07:55Z","timestamp":1748592475000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Investigating the antiproliferative mechanisms of NaHS, a hydrogen sulfide donor, in the SH-SY5Y cell line"],"prefix":"10.1007","volume":"42","author":[{"given":"Ay\u015feg\u00fcl","family":"\u00d6zt\u00fcrk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziad","family":"Joha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neslihan","family":"Ba\u015fg\u00f6z","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet \u015eevki","family":"Ta\u015fk\u0131ran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"issue":"05","key":"2772_CR1","doi-asserted-by":"publisher","first-page":"366","DOI":"10.4149\/BLL_2022_058","volume":"123","author":"B Sahin","year":"2022","unstructured":"Sahin B, G\u00fcne\u015f H, Ozturk A. 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