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Screening various compounds with potential inhibition of cancer stem cells led to the discovery of a naturally occurring Dioscin as a novel ALDH1A3 inhibitor. However, the precise mechanism underlying its action remains unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Procedure<\/jats:title>\n                    <jats:p>\n                      Immunohistochemical analysis of 90 ovarian serous tumor samples revealed the clinical significance of ALDH1A3 in tumor progression. TCGA data was used to identify genes highly correlated with ALDH1A3 in ovarian cancer. Using CRISPR\/Cas9\u2010generated\n                      <jats:italic>ALDH1A3<\/jats:italic>\n                      knockout (KO) cell lines, we investigated its oncogenic influence in ovarian and gastric cancers. The anti\u2010tumor effects of Dioscin were assessed through MTT, scratch, and 3D spheroid formation assays. In\u00a0vivo efficacy of Dioscin was assessed using a xenograft mouse model. Mechanistic investigations of Dioscin with ALDH1A3 were predicted by molecular docking and assessed through ALDH1A3 enzymatic activity and retinoic acid (RA) metabolism analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ALDH1A3 expression correlates with early\u2010stage ovarian cancer progression. Genetic ablation of\n                      <jats:italic>ALDH1A3<\/jats:italic>\n                      significantly suppressed cell proliferation, migration, and stemness properties. ALDH1A3 is significantly associated with ECM\u2010related genes in ovarian cancer. Dioscin exhibited an ALDH1A3\u2010dependent anti\u2010tumor effect by inhibiting ALDH1A3 enzymatic activity, disrupting RA metabolism, and downregulating the expression of stemness\u2010 and migration\u2010associated proteins (CD44 and MMP2). Furthermore, Dioscin effectively delays tumor growth without obvious signs of toxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study provides the first evidence that Dioscin inhibits ALDH1A3\u2010mediated RA metabolism and cancer stemness. Our data will further support its potential as a therapeutic agent for cancer treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ptr.70247","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:21:24Z","timestamp":1770337284000},"page":"1951-1969","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dioscin Suppresses Ovarian and Gastric Tumor Progression by Inhibiting\n                    <scp>ALDH1A3<\/scp>\n                    \u2010Mediated Retinoic Acid Metabolism and Cancer Stemness"],"prefix":"10.1002","volume":"40","author":[{"given":"Kang","family":"Wu","sequence":"first","affiliation":[{"name":"School of Life Sciences Beijing University of Chinese Medicine  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziying","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Sciences Beijing University of Chinese Medicine  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingzheng","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Obstetrics and Gynecology Hospital Capital Medical University. 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