{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T05:38:13Z","timestamp":1762321093036,"version":"build-2065373602"},"reference-count":24,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences","award":["2023-I2M-2-001","2021-1-I2M-030"],"award-info":[{"award-number":["2023-I2M-2-001","2021-1-I2M-030"]}]},{"name":"Beijing Natural Science Foundation","award":["7254505"],"award-info":[{"award-number":["7254505"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pancreatic cancer is an aggressive malignancy with a poor prognosis. It is characterized by low surgical resection rates, frequent development of chemoresistance, unsatisfactory treatment outcomes, and a high potential for recurrence and metastasis. Compound F41, a naturally occurring indole-diterpenoid secondary metabolite, was isolated from the entomopathogenic fungus Penicillium sp. Its anti-pancreatic cancer activity has not been previously reported. Our study demonstrates that F41 significantly inhibits DNA replication, invasion, and proliferation in pancreatic cancer cells. By elevating intracellular reactive oxygen species (ROS) levels in pancreatic cancer cells, F41 induces endoplasmic reticulum stress, ultimately leading to apoptosis. These findings suggest that F41 could effectively overcome gemcitabine resistance in a clinical setting, indicating its promise as a potential therapeutic agent for pancreatic cancer.<\/jats:p>","DOI":"10.3390\/ijms262110694","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:47:58Z","timestamp":1762177678000},"page":"10694","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["F41, a Novel Fungal Indole-Diterpenoid, Overcomes Gemcitabine Resistance in Pancreatic Cancer by Inducing ER Stress"],"prefix":"10.3390","volume":"26","author":[{"given":"Zixiang","family":"Gao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Respiratory Health and Multimorbidity, Key Laboratory of Antibiotic Bioengineering, Ministry of Health, Laboratory of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China"},{"name":"Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Health and Multimorbidity, Key Laboratory of Antibiotic Bioengineering, Ministry of Health, Laboratory of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China"},{"name":"Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cong","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Health and Multimorbidity, Key Laboratory of Antibiotic Bioengineering, Ministry of Health, Laboratory of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China"},{"name":"Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojun","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Health and Multimorbidity, Key Laboratory of Antibiotic Bioengineering, Ministry of Health, Laboratory of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China"},{"name":"Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1126-2754","authenticated-orcid":false,"given":"Yongsheng","family":"Che","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wuli","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Health and Multimorbidity, Key Laboratory of Antibiotic Bioengineering, Ministry of Health, Laboratory of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China"},{"name":"Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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