Oridonin, a diterpenoid purified from Rabdosia rubescens, inhibits the proliferation of cells from lymphoid malignancies in association with blockade of the NF-B signal pathways Takayuki Ikezoe1, Yang Yang1, Kentaro Bandobashi1, Tsuyako Saito1, Shigeki Takemoto1, Hisanori Machida1, Kazuto Togitani1, H. Phillip Koeffler2 and Hirokuni Taguchi1 1 Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Kochi, Japan and 2 Cedars-Sinai Medical Center, University of California at Los Angeles School of Medicine, Los Angeles, California Requests for reprints: Takayuki Ikezoe, Department of Hematology and Respiratory Medicine, KMS, Kochi Medical School, Nankoku, 783-8505 Kochi, Japan. Phone: 81-88-880-2345; Fax: 81-88-880-2348. E-mail: ikezoet@med.kochi-ms.ac.jp This study found that oridonin, a natural diterpenoid purified from Rabdosia rubescens, inhibited growth of multiple myeloma (MM; U266, RPMI8226), acute lymphoblastic T-cell leukemia (Jurkat), and adult T-cell leukemia (MT-1) cells with an effective dose that inhibited 50% of target cells (ED50) ranging from 0.75 to 2.7 µg/mL. Terminal deoxynucleotidyltransferase–mediated dUTP nick end labeling staining showed that oridonin caused apoptosis of MT-1 cells in a time-dependent manner. We explored effects of oridonin on antiapoptotic Bcl-2 family members and found that it down-regulated levels of Mcl-1 and BCL-xL, but not Bcl-2 protein, in both MT-1 and RPMI8226 cells. Further studies found that oridonin inhibited nuclear factor-B (NF-B) DNA-binding activity in these cells as measured by luciferase reporter gene, ELISA-based, and electrophoretic mobility shift assays. Oridonin also blocked tumor necrosis factor-– and lipopolysaccharide-stimulated NF-B activity in Jurkat cells as well as RAW264.7 murine macrophages. Of note, oridonin decreased survival of freshly isolated adult T-cell leukemia (three samples), acute lymphoblastic leukemia (one sample), chronic lymphocytic leukemia (one sample), non-Hodgkin's lymphoma (three samples), and MM (four samples) cells from patients in association with inhibition of NF-B DNA-binding activity. On the other hand, oridonin did not affect survival of normal lymphoid cells from healthy volunteers. Taken together, oridonin might be useful as adjunctive therapy for individuals with lymphoid malignancies, including the lethal disease adult T-cell leukemia. Mol Cancer Ther. 2005;4:578-586 LINK to info on anti-neoplastic /anti bacterial aspects of plant Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.