{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T22:35:20Z","timestamp":1773441320259,"version":"3.50.1"},"reference-count":69,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T00:00:00Z","timestamp":1700524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangdong Marine Economy Development Special Project","award":["GDNRC [2023] 39"],"award-info":[{"award-number":["GDNRC [2023] 39"]}]},{"name":"Guangdong Marine Economy Development Special Project","award":["GDNRC [2022] 35"],"award-info":[{"award-number":["GDNRC [2022] 35"]}]},{"name":"Guangdong Marine Economy Development Special Project","award":["2022A1515011037"],"award-info":[{"award-number":["2022A1515011037"]}]},{"name":"Natural Science Foundation of Guangdong Province, China","award":["GDNRC [2023] 39"],"award-info":[{"award-number":["GDNRC [2023] 39"]}]},{"name":"Natural Science Foundation of Guangdong Province, China","award":["GDNRC [2022] 35"],"award-info":[{"award-number":["GDNRC [2022] 35"]}]},{"name":"Natural Science Foundation of Guangdong Province, China","award":["2022A1515011037"],"award-info":[{"award-number":["2022A1515011037"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Ascomylactam C (AsC) is a new 13-membered-ring macrocyclic alkaloid, which was first isolated and identified in 2019 from the secondary metabolites of the mangrove endophytic fungus Didymella sp. CYSK-4 in the South China Sea. AsC has been found to have a broad-spectrum cytotoxic activity. However, the antitumor effects in vivo and mechanisms of AsC remain unclear. The aim of this study was to describe the effects of AsC on lung cancer and melanoma cells and to explore the antitumor molecular mechanism of AsC. In vitro, we used plate colony formation experiments and demonstrated the ability of AsC to inhibit low-density tumor growth. An Annexin V\/PI cell apoptosis detection experiment revealed that AsC induced tumor cell apoptosis. In vivo, AsC suppressed the tumor growth of LLC and B16F10 allograft significantly in mice, and promoted the infiltration of CD4+ T and CD8+ T cells in tumor tissues. Mechanistically, by analyses of Western blotting, immunofluorescence and ELISA analysis, we found that AsC increased ROS formation, induced endoplasmic reticulum (ER) stress, activated the protein kinase RNA-like ER kinase (PERK)\/eukaryotic translation initiation factor (eIF2\u03b1)\/activating transcription factor 4 (ATF4)\/C\/EBP homologous protein (CHOP) signaling pathway, and induced immunogenic cell death (ICD) of tumor cells. Our results suggest that AsC may be a potentially promising antitumor drug candidate.<\/jats:p>","DOI":"10.3390\/md21120600","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T12:12:13Z","timestamp":1700568733000},"page":"600","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Ascomylactam C Induces an Immunogenic Cell Death Signature via Mitochondria-Associated ER Stress in Lung Cancer and Melanoma"],"prefix":"10.3390","volume":"21","author":[{"given":"Yun","family":"Huang","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China"},{"name":"Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongmei","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China"},{"name":"Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingzhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ge","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China"},{"name":"Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianchen","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuhan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China"},{"name":"Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenxuan","family":"He","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, School of Pharmacy, Anhui Medical University, Hefei 230032, China"},{"name":"School of Chemistry, Sun Yat-sen University, Guangzhou 510275, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxia","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0130-6701","authenticated-orcid":false,"given":"Zhigang","family":"She","sequence":"additional","affiliation":[{"name":"School of Chemistry, Sun Yat-sen University, Guangzhou 510275, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengfeng","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China"},{"name":"Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China"},{"name":"Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4147-5585","authenticated-orcid":false,"given":"Jie","family":"Yuan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China"},{"name":"Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nri.2016.107","article-title":"Immunogenic cell death in cancer and infectious disease","volume":"17","author":"Galluzzi","year":"2017","journal-title":"Nat. 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