{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:05:17Z","timestamp":1790874317905,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T00:00:00Z","timestamp":1650931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81960526"],"award-info":[{"award-number":["81960526"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Secoisolariciresinol diglucoside (SDG) is the main component of lignans with various biological activities, including anticancer activity. However, whether SDG has obvious anticancer effects on colorectal cancer (CRC) is unclear. Pyroptosis, a form of programmed cell death, has received increasing attention in cancer\u2010related research. In this study, we aimed to test the anticancer properties and relatecd functional mechanisms of SDG. we found that SDG not only inhibited the cell viability of HCT116 cells, but also induced HCT116 cells to swell with apparent large bubbles, which are typical signs of pyroptosis. Furthermore, SDG induced cell pyroptosis by enhancing cleavage of the N\u2010terminal fragment of gasdermin D (GSDMD) in CRC cells, accompanied by increased caspase\u20101 cleavage. Consistent with this, SDG\u2010induced GSDMD\u2010N\u2010terminal fragment cleavage and pyroptosis were reduced by siRNA\u2010mediated silencing of caspase\u20101 or treatment with the specific caspase\u20101 inhibitor VX\u2010765 treatment, suggesting that active caspase\u20101 further induces pyroptosis. A mechanistic study showed that SDG induced reactive oxygen species (ROS) accumulation and inhibits phosphatidylinositol 3\u2010kinase (PI3K) phosphorylation and increases pyroptosis, while increasing GSDMD and caspase\u20101 cleavage and enhancing expression of BCL2\u2010associated X (BAX), which could be rescued by the ROS scavenger (NAC), suggesting that SDG\u2010induced GSDME\u2010dependent pyroptosis is related to the ROS\/PI3K\/AKT\/BAX\u2010mitochondrial apoptotic pathway. In vivo results showed that SDG significantly inhibited tumor growth and induced pyroptosis in the HCT116\u2010CRC nude mouse model. In conclusion, our findings suggest that the anticancer activity of SDG in CRC is associated with the induction of GSDMD\u2010dependent pyroptosis by SDG through the generation of ROS\/P13K\/AKT\/BAK\u2010mitochondrail apoptosis pathway, providing insights into SDG in its potential new application in cancer treatment.<\/jats:p>","DOI":"10.1002\/ddr.21939","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T13:29:50Z","timestamp":1650979790000},"page":"1152-1166","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Secoisolariciresinol diglucoside induces pyroptosis by activating caspase\u20101 to cleave GSDMD in colorectal cancer cells"],"prefix":"10.1002","volume":"83","author":[{"given":"Tuo","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Burn and Plastic Surgery Zigong Fourth People's Hospital  Zigong Sichuan China"},{"name":"Department of Colorectal 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