Gamma-tocopheryl quinone stimulates apoptosis in drug-sensitive and multidrug-resistant cancer cells

Lipids
Kenneth H JonesDavid G Cornwell

Abstract

Chemotherapy-induced cell death is linked to apoptosis, and there is increasing evidence that multidrug-resistance in cancer cells may be the result of a decrease in the ability of a cell to initiate apoptosis in response to cytotoxic agents. In previous studies, we synthesized two classes of electrophilic tocopheryl quinones (TQ), nonarylating alpha-TQ and arylating gamma- and delta-TQ, and found that gamma- and delta-TQ, but not alpha-TQ, were highly cytotoxic in human acute lymphoblastic leukemia cells (CEM) and multidrug-resistant (MDR) CEM/VLB100. We have now extended these studies on tumor biology with CEM, HL60 and MDR HL60/MX2 human promyelocytic leukemia, U937 human monocytic leukemia, and ZR-75-1 breast adenocarcinoma cells. gamma-TQ, but not alpha-TQ or tocopherols, showed concentration and incubation time-dependent 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-associated 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. Gamma-TQ rele...Continue Reading

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Citations

Mar 15, 2003·Chemistry and Physics of Lipids·Yasukazu YoshidaNoriko Noguchi
Dec 15, 2004·Proceedings of the National Academy of Sciences of the United States of America·Qing JiangBruce N Ames
Jul 17, 2004·Annals of Nutrition & Metabolism·Karl-Heinz WagnerIbrahim Elmadfa
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Mar 9, 2005·Annals of the New York Academy of Sciences·Achim Stocker
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Dec 18, 2009·Chemical Research in Toxicology·Andrea MüllebnerLars Gille
Sep 12, 2008·Journal of Agricultural and Food Chemistry·David G Cornwell, Jiyan Ma

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