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The underlying molecular mechanisms were investigated, involving the analysis of the TRPV1-PLC\u03b3-NOX4 and PERK-ATF3-JMJD2C-SLC7A11-GPX4 signaling pathways. The functional role of ATF3 was further validated using gene knockdown approaches and promoter-binding assays. In addition, the\n                      <jats:italic>in vivo<\/jats:italic>\n                      therapeutic efficacy of 8-gingerol was assessed using a xenograft mouse model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Treatment with 8-gingerol significantly reduced cell viability and intracellular GSH levels, while increasing caspase-3 activity, LDH release, ROS generation, and MDA levels. These molecular and cellular effects were associated with marked inhibition of tumor growth\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Mechanistically, 8-gingerol induced intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      accumulation and ROS production, thereby promoting endoplasmic reticulum (ER) stress-mediated apoptotic and ferroptotic cell death. This process was mediated in a manner involving activation of the TRPV1-PLC\u03b3-NOX4 axis and ATF3-dependent suppression of SLC7A11 via the histone demethylase JMJD2C. Importantly, pharmacological inhibition of ROS or genetic targeting of ATF3 significantly attenuated 8-gingerol-induced cell death, confirming the critical functional roles of these signaling pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings demonstrate that 8-gingerol induces coordinated apoptotic and ferroptotic cell death through a Ca\n                      <jats:sup>2+<\/jats:sup>\n                      -dependent ER stress mechanism, highlighting its potential as a novel therapeutic strategy for the treatment of ovarian cancer.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12964-026-03014-8","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T03:46:26Z","timestamp":1783655186000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["8-gingerol from Zingiber officinale induces ER stress-mediated ferroptosis and apoptosis in ovarian cancer involving TRPV1 activation"],"prefix":"10.1186","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6737-2739","authenticated-orcid":false,"given":"Tae Woo","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"3014_CR1","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.ygyno.2010.01.041","volume":"117","author":"L Cheng","year":"2010","unstructured":"Cheng L, et al. 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