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In previous studies, we synthesized two classes of electrophilic tocopheryl quinones (TQ), nonarylating \u03b1\u2010TQ and arylating \u03b3\u2010and \u03b4\u2010TQ, and found that \u03b3\u2010and \u03b4\u2010TQ, but not \u03b1\u2010TQ, were highly cytotoxic in human acute lymphoblastic leukemia cells (CEM) and multidrug\u2010resistant (MDR) CEM\/VLB<jats:sub>100<\/jats:sub>. We have now extended these studies on tumor biology with CFM, HL60 and MDR HL60\/MX2 human promyelocytic leukemia, U937 human monocytic leukemia, and ZR\u201075\u20101 breast adenocarcinoma cells. \u03b3\u2010TQ, but not \u03b1\u2010TQ or tocopherols, showed concentration and incubation time\u2010dependent effects on loss of plasma membrane integrity, diminished viable cell number, and stimulation of apoptosis. Its cytotoxicity exceeded that of doxorubicin in HL60\/MX2 cells, which express MRP, an MDR\u2010associated protein. Apoptosis was confirmed by TEM, TUNEL, and DNA gel electrophoresis. Kinetic studies showed that an induction period was required to initiate an irreversible multiphase process. \u03b3\u2010TQ released mitochondrial cytochrome c to the cytosol, induced the cleavage of poly(ADP\u2010ribose)polymerase, and depleted intracellular glutathione. Unlike xenobiotic electrophiles, \u03b3\u2010TQ is a highly cytotoxic arylating electrophile that stimulates apoptosis in several cancer cell lines including cells that express MDR through both P\u2010glycoprotein and MRP\u2010associated proteins. The biological properties of arylating TQ electrophiles are closely associated with cytotoxicity and may contribute to other biological effects of these highly active agents.<\/jats:p>","DOI":"10.1007\/s11745-002-0878-2","type":"journal-article","created":{"date-parts":[[2006,11,13]],"date-time":"2006-11-13T18:49:57Z","timestamp":1163443797000},"page":"173-184","source":"Crossref","is-referenced-by-count":21,"title":["\u03b3\u2010Tocopheryl quinone stimulates apoptosis in drug\u2010sensitive and multidrug\u2010resistant cancer cells"],"prefix":"10.1002","volume":"37","author":[{"given":"Kenneth H.","family":"Jones","sequence":"first","affiliation":[{"name":"Department of Anatomy and Medical Education, College of Medicine and Public Health The Ohio State University 333 W. 10th Avenue Columbus OH 43210"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer J.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Medical Education, 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