{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T16:23:03Z","timestamp":1775492583633,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,3,18]],"date-time":"2016-03-18T00:00:00Z","timestamp":1458259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"China Medical University, Taichung, Taiwan","award":["CMU103-ASIA-01"],"award-info":[{"award-number":["CMU103-ASIA-01"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Triptolide, a traditional Chinese medicine, obtained from <jats:italic>Tripterygium wilfordii<\/jats:italic> Hook F, has anti\u2010inflammatory, antiproliferative, and proapoptotic properties. We investigated the potential efficacy of triptolide on murine leukemia by measuring the triptolide\u2010induced cytotoxicity in murine leukemia WEHI\u20103 cells <jats:italic>in vitro<\/jats:italic>. Results indicated that triptolide induced cell morphological changes and induced cytotoxic effects through G0\/G1 phase arrest, induction of apoptosis. Flow cytometric assays showed that triptolide increased the production of reactive oxygen species, Ca<jats:sup>2+<\/jats:sup> release and mitochondrial membrane potential (\u0394<jats:italic>\u03a8<\/jats:italic><jats:sub>m<\/jats:sub>), and activations of caspase\u20108, \u20109, and \u20103. Triptolide increased protein levels of Fas, Fas\u2010L, Bax, cytochrome c, caspase\u20109, Endo G, Apaf\u20101, PARP, caspase\u20103 but reduced levels of AIF, ATF6\u03b1, ATF6\u03b2, and GRP78 in WEHI\u20103 cells. Triptolide stimulated autophagy based on an increase in acidic vacuoles, monodansylcadaverine staining for LC\u20103 expression and increased protein levels of ATG 5, ATG 7, and ATG 12. The <jats:italic>in vitro<\/jats:italic> data suggest that the cytotoxic effects of triptolide may involve cross\u2010talk between cross\u2010interaction of apoptosis and autophagy. Normal BALB\/c mice were i.p. injected with WEHI\u20103 cells to generate leukemia and were oral treatment with triptolide at 0, 0.02, and 0.2 mg\/kg for 3 weeks then animals were weighted and blood, liver, spleen samples were collected. Results indicated that triptolide did not significantly affect the weights of animal body, spleen and liver of leukemia mice, however, triptolide significant increased the cell populations of T cells (CD3), B cells (CD19), monocytes (CD11b), and macrophage (Mac\u20103). Furthermore, triptolide increased the phagocytosis of macrophage from peripheral blood mononuclear cells (PBMC) but not effects from peritoneum. Triptolide promoted T and B cell proliferation at 0.02 and 0.2 mg\/kg treatment when cells were pretreated with Con A and LPS stimulation, respectively; however, triptolide did not significant affect NK cell activities <jats:italic>in vivo<\/jats:italic>. \u00a9 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 550\u2013568, 2017.<\/jats:p>","DOI":"10.1002\/tox.22259","type":"journal-article","created":{"date-parts":[[2016,3,19]],"date-time":"2016-03-19T07:20:56Z","timestamp":1458372056000},"page":"550-568","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Triptolide induced cell death through apoptosis and autophagy in murine leukemia WEHI\u20103 cells <i>in vitro<\/i> and promoting immune responses in WEHI\u20103 generated leukemia mice <i>in vivo<\/i>"],"prefix":"10.1002","volume":"32","author":[{"given":"Shih\u2010Feng","family":"Chan","sequence":"first","affiliation":[{"name":"Department of Biological Science and Technology China Medical University Taichung 404 Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya\u2010Yin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Chinese\u2010Western Medicine Integration Chung Shan Medical University 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