{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T03:07:05Z","timestamp":1773630425192,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T00:00:00Z","timestamp":1560988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 21372191, 30800182 & 30701045"],"award-info":[{"award-number":["No. 21372191, 30800182 & 30701045"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Science and Technology Innovation Training Fund of Yangzhou University","award":["No. 2012CXJ097 & 2011CXJ081"],"award-info":[{"award-number":["No. 2012CXJ097 & 2011CXJ081"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Trichothecene macrolides comprise a class of valuable leading compounds in developing anticancer drugs, however, there are few reports concerning their anticancer mechanisms, especially the anticancer mechanism of the 10,13-cyclotrichothecane derivatives that are found mainly in symbiotic fungi. In vitro anticancer activity of two trichothecene macrolides mytoxin B and myrothecine A against the human hepatocarcinoma cell line SMMC-7721 was investigated in the present study. MTT assay showed that mytoxin B and myrothecine A inhibited the proliferation of SMMC-7721 cells in dose- and time-dependent manners. Annexin V-FITC\/PI dual staining assay revealed that mytoxin B and myrothecine A both could induce SMMC-7721 cells apoptosis in a dose-dependent manner. The decreased expression level of anti-apoptotic protein Bcl-2 and the increased expression level of pro-apoptotic protein Bax were observed apparently in Western blot analysis. The reduced ratio of Bcl-2\/Bax further confirmed the apoptosis-inducing effect of mytoxin B and myrothecine A on SMMC-7721 cells. Moreover, the expression levels of caspases-3, -8, and -9, and cleaved caspases-3, -8, and -9 were all upregulated in both mytoxin B and myrothecine A-treated cells in Western blot analysis, which indicated that both compounds might induce SMMC-7721 cells apoptosis through not only the death receptor pathway but also the mitochondrial pathway. Finally, mytoxin B and myrothecine A were found to reduce the activity of PI3K\/Akt signaling pathway that was similar to the effect of LY294002 (a potent and specific PI3K inhibitor), suggesting that both mytoxin B and myrothecine A might induce SMMC-7721 cells apoptosis via PI3K\/Akt pathway.<\/jats:p>","DOI":"10.3390\/molecules24122291","type":"journal-article","created":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T10:49:59Z","timestamp":1561027799000},"page":"2291","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mytoxin B and Myrothecine A Induce Apoptosis in Human Hepatocarcinoma Cell Line SMMC-7721 via PI3K\/Akt Signaling Pathway"],"prefix":"10.3390","volume":"24","author":[{"given":"Huiliang","family":"Song","sequence":"first","affiliation":[{"name":"Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, China"},{"name":"Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou 225001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Fu","sequence":"additional","affiliation":[{"name":"School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Wan","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjing","family":"Xia","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengwei","family":"Lyu","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijun","family":"Liu","sequence":"additional","affiliation":[{"name":"Jiangsu Co-Innovation Center for Modern Production Technology of Grain Crops\/Jiangsu Key Laboratory of Crop Genetics and Physiology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Shen","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, China"},{"name":"Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou 225001, China"},{"name":"Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5596","DOI":"10.1002\/chem.200600084","article-title":"Absolute configuration of new cytotoxic and other bioactive trichothecene macrolides","volume":"12","author":"Shen","year":"2006","journal-title":"Chem. 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