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Fluorouracil (5\u2010FU) is currently used as an anticancer drug for leukemia patients. Casticin, a natural polymethoxyflavone, exerts anticancer activity against many human cancer cell lines in vitro, but no other reports show 5\u2010FU combined with casticin increased the mouse leukemia cell apoptosis in vitro. Herein, the antileukemia activity of 5\u2010FU combined with casticin in WEHI\u20103 mouse leukemia cells was investigated in vitro<jats:italic>.<\/jats:italic> Treatment of two\u2010drug combination had a higher decrease in cell viability and a higher increase in apoptotic cell death, the level of DNA condensation, and the length of comet tail than that of 5\u2010FU or casticin treatment alone in WEHI\u20103 cells. In addition, the two\u2010drug combination has a greater production rate of reactive oxygen species but a lower level of Ca<jats:sup>2+<\/jats:sup> release and mitochondrial membrane potential (\u0394\u03a8<jats:sub>m<\/jats:sub>) than that of 5\u2010FU alone. Combined drugs also induced higher caspase\u20103 and caspase\u20108 activities than that of casticin alone and higher caspase\u20109 activity than that of 5\u2010FU or casticin alone at 48\u2009hours treatment. Furthermore, 5\u2010FU combined with casticin has a higher expression of Cu\/Zn superoxide dismutase (SOD [Cu\/Zn]) and lower catalase than that of 5\u2010FU or casticin treatment alone. The combined treatment has higher levels of Bax, Endo G, and cytochrome C of proapoptotic proteins than that of casticin alone and induced lower levels of B\u2010cell lymphoma 2 (BCL\u20102) and BCL\u2010X of antiapoptotic proteins than that of 5\u2010FU or casticin only. Furthermore, the combined treatment had a higher expression of cleaved poly (ADP\u2010ribose) polymerase (PARP) than that of casticin only. Based on these findings, we may suggest that 5\u2010FU combined with casticin treatment increased apoptotic cell death in WEHI\u20103 mouse leukemia cells that may undergo mitochondria and caspases signaling pathways in vitro.<\/jats:p>","DOI":"10.1002\/tox.22927","type":"journal-article","created":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T11:33:25Z","timestamp":1586432005000},"page":"911-921","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Combinational treatment of 5\u2010fluorouracil and casticin induces apoptosis in mouse leukemia <scp>WEHI<\/scp>\u20103 cells in vitro"],"prefix":"10.1002","volume":"35","author":[{"given":"Zheng\u2010Yu","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Biological Science and Technology China Medical University  Taichung 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