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Depression: 21st Century Solutions + The Dark Side of Wheat

Abstract Title:

Triptolide induces caspase-dependent cell death mediated via the mitochondrial pathway in leukemic cells.

Abstract Source:

Blood. 2006 Jul 15;108(2):630-7. Epub 2006 Mar 23. PMID: 16556893

Abstract Author(s):

Bing Z Carter, Duncan H Mak, Wendy D Schober, Teresa McQueen, David Harris, Zeev Estrov, Randall L Evans, Michael Andreeff

Abstract:

Triptolide, a diterpenoid isolated from the Chinese herb Tripterygium wilfordii Hook.f, has shown antitumor activities in a broad range of solid tumors. Here, we examined its effects on leukemic cells and found that, at 100 nM or less, it potently induced apoptosis in various leukemic cell lines and primary acute myeloid leukemia (AML) blasts. We then attempted to identify its mechanisms of action. Triptolide induced caspase-dependent cell death accompanied by a significant decrease in XIAP levels. Forced XIAP overexpression attenuated triptolide-induced cell death. Triptolide also decreased Mcl-1 but not Bcl-2 and Bcl-X(L) levels. Bcl-2 overexpression suppressed triptolide-induced apoptosis. Further, triptolide induced loss of the mitochondrial membrane potential and cytochrome C release. Caspase-9 knock-out cells were resistant, while caspase-8-deficient cells were sensitive to triptolide, suggesting criticality of the mitochondrial but not the death receptor pathway for triptolide-induced apoptosis. Triptolide also enhanced cell death induced by other anticancer agents. Collectively, our results demonstrate that triptolide decreases XIAP and potently induces caspase-dependent apoptosis in leukemic cells mediated through the mitochondrial pathway at low nanomolar concentrations. The potent antileukemic activity of triptolide in vitro warrants further investigation of this compound for the treatment of leukemias and other malignancies.

Study Type : In Vitro Study

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Sayer Ji
Founder of GreenMedInfo.com

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Depression: 21st Century Solutions + The Dark Side of Wheat

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