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However, its therapeutic efficacy against acute lymphoblastic leukemia (ALL) remains underexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      ALL cell lines and normal bone marrow mononuclear cells were treated with Vitamin C to assess cell viability, apoptosis, proliferation, and cell cycle progression. Colony formation assays evaluated long-term growth. Additionally, transgenic mouse models were employed to evaluate the\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      antitumor activity of high-dose Vitamin C in ALL. Western blotting, ROS detection 2\u2032,7\u2032-Dichlorofluorescin diacetate (DCFH-DA), and RNA sequencing with GSEA were conducted to explore Vitamin C\u2019s mechanism of action.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results demonstrated that high-dose Vitamin C exhibited potent cytotoxicity toward ALL cells at relatively low concentrations (200\u00a0\u03bcM) while sparing normal human bone marrow mononuclear cells even at concentrations as high as 1\u00a0mM. Vitamin C effectively inhibited ALL cell line proliferation, induced apoptosis, and disrupted cell cycle progression. We further identified that the increased expression of Solute Carrier Family 23 Member 1 (SLC23A1) in ALL cells enhanced their sensitivity to Vitamin C. In SLC23A1 knockout cells, treatment with 200\u00a0\u03bcM Vitamin C significantly restored cell viability and reduced apoptosis compared to controls. Mechanistically, high-dose Vitamin C induced apoptosis in ALL cells by activating the ER stress response through the PERK\/CHOP pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Taken together, our findings suggest that high-dose Vitamin C demonstrated significant anti-leukemic effects in ALL, showing cytotoxicity at 200\u00a0\u03bcM. Furthermore, SLC23A1 may serve as a potential biomarker for predicting the therapeutic response to Vitamin C treatment in ALL patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/09603271251345656","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T01:21:09Z","timestamp":1748568069000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["High-dose vitamin C potently induces apoptosis in acute lymphoblastic leukemia by activating ER stress response"],"prefix":"10.1177","volume":"44","author":[{"given":"Hui meng","family":"Sun","sequence":"first","affiliation":[{"name":"Tianjin Medical University Cancer Institute and Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8964-7155","authenticated-orcid":false,"given":"Yanan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Nankai University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiping","family":"Luo","sequence":"additional","affiliation":[{"name":"Tianjin Medical University Cancer Institute and Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong hui","family":"Xing","sequence":"additional","affiliation":[{"name":"Tianjin Medical University Cancer Institute and Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Zhai","sequence":"additional","affiliation":[{"name":"Tianjin Medical University Cancer Institute and Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"He","sequence":"additional","affiliation":[{"name":"Tianjin Medical University Cancer Institute and Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqi","family":"Wu","sequence":"additional","affiliation":[{"name":"Tianjin Medical University Cancer Institute and Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Tianjin Medical University Cancer Institute and Hospital"},{"name":"Nankai University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.59.1636"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-05-038950"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)33018-1"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpls.2018.02006"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232012249"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11041060"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0135-7"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-020-01738-0"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.07.032"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-023-01954-5"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2012.08.004"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-0788-8"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1TA0214-121RR"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2015.01.004"},{"key":"e_1_3_7_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.3.805"},{"key":"e_1_3_7_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-010-9441-3"},{"key":"e_1_3_7_18_2","doi-asserted-by":"publisher","DOI":"10.1177\/1534735416681639"},{"key":"e_1_3_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2017.12.028"},{"key":"e_1_3_7_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-019-04598-w"},{"key":"e_1_3_7_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu12051351"},{"key":"e_1_3_7_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature17041"},{"key":"e_1_3_7_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.18030"},{"key":"e_1_3_7_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1101"},{"key":"e_1_3_7_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/19.2.185"},{"key":"e_1_3_7_26_2","doi-asserted-by":"crossref","unstructured":"Larriba Y Rueda C Fern\u00e1ndez MA et al. 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