Triptolide displayed potent antileukemic activity

10-05-2006

Triptolide, a diterpenoid isolated from the Chinese herb Tripterygium wilfordii Hook.f, displayed potent antileukemic activity.

"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," scientists in the United States reported.

"We then attempted to identify its mechanisms of action," explained B.Z. Carter and colleagues, M.D. Anderson Cancer Center. "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 researchers concluded, "The potent antileukemic activity of triptolide in vitro warrants further investigation of this compound for the treatment of leukemias and other malignancies."

Carter and colleagues published their study in Blood (Triptolide induces caspase-dependent cell death mediated via the mitochondrial pathway in leukemic cells. Blood, 2006;108(2):630-637).

For additional information, contact M. Andreeff, University of Texas, M.D. Anderson Cancer Center, Sect Molecular Hematology & Therapy, Dept. of Blood & Marrow Transplantation, Unit 448, 1515 Holcombe Blvd., Houston, TX 77030, USA.

The publisher's contact information for the journal Blood is: American Society Hematology, 1900 M Street. NW Suite 200, Washington, DC 20036, USA.

Keywords: Houston, Texas, United States, Acute Myeloid Leukemia, Complementary & Alternative Medicine, Anticancer Therapy, Apoptosis, Oncology, Solid Cancers, Solid Carcinomas, Diterpenoid, Chinese Herb, Tripterygium wilfordii Hook.f.

This article was prepared by Hematology Week editors from staff and other reports. Copyright 2006, Hematology Week via NewsRx.com.