{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T13:15:29Z","timestamp":1774876529364,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003718","name":"Korea Institute of Oriental Medicine\n\t\t\t\t\t\t\t\t              https:\/\/ror.org\/005rpmt10","doi-asserted-by":"publisher","award":["KSN2026240"],"award-info":[{"award-number":["KSN2026240"]}],"id":[{"id":"10.13039\/501100003718","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Plant-derived saponins have attracted significant interest for their potential to promote apoptotic cell death and enhance antitumor immune responses through immunogenic cell death (ICD). Akebia quinata, a saponin-rich medicinal plant, exhibits diverse pharmacological properties; however, studies on its seeds are limited, and their immunomodulatory activity in cancer remains largely unexplored. In this study, A. quinata seeds were extracted using 70% ethanol, and the phytochemical profile was characterized using UHPLC\u2013QTOF MS\/MS. We investigated the anticancer properties of A. quinata seed extract (AQSE), focusing on its role in inducing apoptosis and ICD in non-small cell lung cancer (NSCLC). In human NSCLC cell lines (A549 and H460), AQSE exhibited potent cytotoxic effects in a dose-dependent manner. Flow cytometric analysis confirmed the induction of apoptosis, evidenced by a significant increase in Annexin V-positive cells and an elevated sub-G1 population. Mechanistically, AQSE treatment induced cell death by simultaneously inhibiting the survival-promoting MEK\/ERK\/CREB axis and activating the stress-responsive JNK pathway. Furthermore, AQSE triggered hallmark features of ICD, characterized by surface exposure of calreticulin and the release of extracellular HMGB1 and ATP. Most importantly, an in vivo vaccination assay using a syngeneic mouse model demonstrated that immunization with AQSE-treated dying cells significantly suppressed tumor growth upon rechallenge, confirming the establishment of antitumor immunological memory. Additionally, bioassay-guided fractionation revealed that the anticancer activity was primarily concentrated in the ethyl acetate fraction. These findings suggest that AQSE exerts anticancer effects via the induction of apoptosis and ICD, highlighting its potential as a promising natural candidate for the development of novel therapeutic strategies against NSCLC.<\/jats:p>","DOI":"10.3390\/ijms27073114","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T12:11:59Z","timestamp":1774872719000},"page":"3114","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Effects of Akebia quinata Seeds Through Apoptosis and Immunogenic Cell Death in Non-Small Cell Lung Cancer"],"prefix":"10.3390","volume":"27","author":[{"given":"Mibae","family":"Jeong","sequence":"first","affiliation":[{"name":"KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea"},{"name":"Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9210-1401","authenticated-orcid":false,"given":"In Jin","family":"Ha","sequence":"additional","affiliation":[{"name":"Korean Medicine Clinical Trial Center (K-CTC), Korean Medicine Hospital, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8156-446X","authenticated-orcid":false,"given":"Chang-Seob","family":"Seo","sequence":"additional","affiliation":[{"name":"KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0239-0159","authenticated-orcid":false,"given":"Mi-Kyung","family":"Jeong","sequence":"additional","affiliation":[{"name":"KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2882-0612","authenticated-orcid":false,"given":"Kwang Seok","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4191-4063","authenticated-orcid":false,"given":"Jaemoo","family":"Chun","sequence":"additional","affiliation":[{"name":"KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea"},{"name":"KIOM School, University of Science & Technology (UST), Daejeon 34054, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1002\/cncr.35128","article-title":"Lung cancer statistics, 2023","volume":"130","author":"Kratzer","year":"2024","journal-title":"Cancer"},{"key":"ref_2","first-page":"12","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. 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