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The secondary metabolites of this genus exhibit many biological activities, including antifungal activity and toxicity in mitochondria. In this study, we isolated cristazine from the fungus <jats:styled-content style=\"fixed-case\"><jats:italic>C. cristatum<\/jats:italic><\/jats:styled-content>, which has the potential to inhibit the growth of human epidermoid carcinoma (A431) cells in a dose\u2010 and time\u2010dependent manner. Its inhibitory activity was examined using a cell viability assay and cell death was elucidated by western blot analysis. Cristazine triggered apoptotic cell death via the Type I death receptor pathway including the activation of caspases and other target proteins. However, cristazine did not have any effect on mitochondrial apoptotic proteins such as Bid, cytochrome <jats:italic>c<\/jats:italic>, and apoptosis\u2010inducing factor. Cristazine inhibited the cell cycle progression by arresting the G<jats:sub>1<\/jats:sub>\/S phase and up\u2010regulating the inhibitory proteins of cyclin\u2010dependent kinases. Thus, cristazine has great potential for inducing apoptosis in A431 cells via both cell cycle arrest and the inhibition of cell growth.<\/jats:p>","DOI":"10.1002\/ddr.21527","type":"journal-article","created":{"date-parts":[[2019,3,12]],"date-time":"2019-03-12T11:11:03Z","timestamp":1552389063000},"page":"504-512","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Cristazine, a novel dioxopiperazine alkaloid, induces apoptosis via the death receptor pathway in A431 cells"],"prefix":"10.1002","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7289-6203","authenticated-orcid":false,"given":"Mi Jeong","family":"Jo","sequence":"first","affiliation":[{"name":"Department of Microbiology College of Natural Sciences, Pukyong National University  Busan Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5303-5985","authenticated-orcid":false,"given":"Maheshkumar P.","family":"Patil","sequence":"additional","affiliation":[{"name":"Department of Microbiology College of Natural Sciences, Pukyong National University  Busan Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun Il","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Microbiology College of Natural Sciences, Pukyong National University  Busan Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong Bae","family":"Seo","sequence":"additional","affiliation":[{"name":"Institute of Marine Biotechnology Pukyong National University  Busan Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han Kyu","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Marine and Fisheries Resources College of Natural Sciences, Mokpo National University  Muan Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byeng Wha","family":"Son","sequence":"additional","affiliation":[{"name":"Department of Chemistry College of Natural Sciences, Pukyong National University  Busan Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5965-0495","authenticated-orcid":false,"given":"Gun\u2010Do","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Microbiology College of Natural Sciences, Pukyong National University  Busan Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,3,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.5826\/dpc.0702a01"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13555-016-0165-y"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1305"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13402-013-0157-1"},{"issue":"9","key":"e_1_2_6_6_1","first-page":"2083","article-title":"Mistletoe lectin activates caspase\u20108\/FLICE independently of death receptor signaling and enhances anticancer drug\u2010induced apoptosis","volume":"59","author":"Bantel H.","year":"1999","journal-title":"Cancer Research"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.33.22932"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-9-449"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2015.038"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400883"},{"key":"e_1_2_6_11_1","first-page":"160","article-title":"Bioactive marine natural products","volume":"31","author":"Desjardine K. 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