{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T17:46:04Z","timestamp":1776361564867,"version":"3.51.2"},"reference-count":47,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Resistance to primary chemotherapeutics poses a significant challenge in treating solid tumors. The majority of the second\u2010line chemo and targeted therapeutics act moderately\/less effectively in drug\u2010resistant tumors owing to the multicausal nature of drug resistance. Therefore, a single agent with pleiotropic effects would be beneficial in combating this adversity.\n                    <jats:italic>Withania somnifera<\/jats:italic>\n                    exhibits multifunctional anticancer properties, but its role in overcoming chemoresistance remains poorly understood. We evaluated the cytotoxic effect of Ashwamax\n                    <jats:sup>TM<\/jats:sup>\n                    \u2010\n                    <jats:italic>W. somnifera<\/jats:italic>\n                    (WS)\u2014extract and Withaferin A (WFA), in intrinsically resistant (KATO\u2010III and SKOV3) and acquired chemoresistant gastric (AGS\n                    <jats:sup>5FU<\/jats:sup>\n                    ) and ovarian (A2780\n                    <jats:sup>LR<\/jats:sup>\n                    ) cancer cellular models. We examined their impact on autophagy and apoptosis pathways and elucidated the underlying molecular mechanism. In vivo efficacy of WFA on cisplatin\u2010paclitaxel\u2010resistant epithelial ovarian cancer (EOC)\u00a0xenografts was assessed using noninvasive optical imaging. Mechanistically, WFA is more proficient in targeting chemoresistant cells than Ashwamax\n                    <jats:sup>TM<\/jats:sup>\n                    \u2010WS extract and activates apoptosis by overriding the AKT\u2013NF\u2010\u03baB\u2013STAT3\u2013survivin axis. Preclinical imaging revealed dose\u2010dependent tumor regression (during and after treatment) in platinum\u2010taxol\u2010resistant EOC xenografts that were unresponsive to cisplatin challenge. WFA, at\u00a03\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    dosage, reduced tumor volume by 4.7\u2010fold compared to controls, with sustained antitumor effects persisting after treatment cessation. WFA effectively targets the AKT\u2013NF\u2010\u03baB\u2013STAT3\u2013survivin axis to overcome single and multidrug resistance in gastric and epithelial ovarian cancers, presenting a promising therapeutic alternative for chemoresistant malignancies.\n                  <\/jats:p>","DOI":"10.1002\/mc.70043","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T13:34:37Z","timestamp":1759239277000},"page":"2037-2051","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Withaferin A Exerts Cytotoxicity in Single\/Multidrug\u2010Resistant Gastric and Ovarian Cancer Cells and Tumor Xenografts Through the AKT\u2013NF\u2010\u03baB\u2013STAT3\u2013Survivin Axis"],"prefix":"10.1002","volume":"64","author":[{"given":"Priti S.","family":"Shenoy","sequence":"first","affiliation":[{"name":"Imaging Cell Signaling &amp; Therapeutics Lab, Advanced Centre for Treatment, Research and Education in Cancer Tata Memorial Centre Navi Mumbai India"},{"name":"Homi Bhabha National Institute Mumbai India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shubhankar","family":"Dash","sequence":"additional","affiliation":[{"name":"Imaging Cell Signaling &amp; Therapeutics Lab, Advanced Centre for Treatment, Research and Education in Cancer Tata Memorial Centre Navi Mumbai India"},{"name":"Department of Experimental Hematology Institute of Hematology &amp; Transfusion Medicine Warsaw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diksha","family":"Joshi","sequence":"additional","affiliation":[{"name":"Imaging Cell Signaling &amp; Therapeutics Lab, Advanced Centre for Treatment, Research and Education in Cancer Tata Memorial Centre Navi Mumbai India"},{"name":"Homi Bhabha National Institute Mumbai India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bharat","family":"Rekhi","sequence":"additional","affiliation":[{"name":"Homi Bhabha National 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