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This study investigated SAMA and cisplatin's combined effects and underlying ROS\/MAPK mechanisms of action on oral cancer cells. The combination significantly reduced viability (ATP assay) in oral cancer Ca9\u201122 and CAL 27 cells compared with either agent alone, with synergistic indices confirming enhanced antiproliferation. Moreover, this combination markedly suppressed colony formation and cell migration. SAMA\/cisplatin induced subG1 accumulation and G2\/M arrest, elevated cellular and mitochondrial ROS, and promoted apoptosis, as evidenced by increased annexin V positivity and caspase\u20113, \u20108, and \u20109 activation, while DNA damage markers \u03b3H2AX and 8\u2011OHdG were also markedly elevated. In contrast, normal oral S\u2011G cells showed minimal cytotoxic damage and mechanical changes, suggesting selectivity. Mechanistically, JNK inhibition rescued the antiproliferative response and suppressed apoptosis, caspase activation, and DNA damage. Pretreatment with the ROS scavenger NAC attenuated all test effects, confirming ROS dependence. Together, these findings demonstrate that SAMA synergizes with cisplatin to selectively enhance oxidative stress, apoptosis, and DNA damage in oral cancer cells via ROS\u2011dependent JNK signaling, highlighting its potential as a cisplatin adjunct.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70327","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T13:27:16Z","timestamp":1779802036000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Santamarine Synergizes With Cisplatin via ROS\/JNK Axis to Selectively Induce Apoptosis and DNA Damage in Oral Cancer Cells In Vitro"],"prefix":"10.1002","volume":"87","author":[{"given":"Hsin\u2010I.","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Biomedical Science and Environmental Biology, PhD Program in Life Sciences, College of Life Sciences Kaohsiung Medical University Kaohsiung 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