Oridonin-induced apoptosis in leukemia K562 cells and its mechanism.
Oridonin, an extract from the Chinese herb Rabdosia rubescens, is currently one of the most important traditional Chinese herbal medicines. Recently oridonin has been reported to have anti- tumor effects in a large variety of malignant diseases. In this study, we investigated the apoptotic inducing effect of oridonin in leukemia K562 cells and its mechanism. Cell growth inhibition was measured using a microculture tetrazolium assay, apoptosis was measured by flow cytometry and electron microscopy as well as by DNA fragmentation analysis. Telomerase activity was measured by TRAP-enzyme- linked immunosorbent assay, and the expression of Bcl-2 and Bax proteins was detected by western blot analysis. The results showed that oridonin could inhibit the proliferation and induce apoptosis on leukemia K562 cells remarkably. Telomerase activity as well as Bcl-2 expression was down- regulated, while Bax expression was up-regulated concurrently, when apoptosis ocurred. We therefore conclude that oridonin demonstrated anti-proliferative and apoptosis-inducing effects on K562 cells in vitro, and that changes in bcl-2 and bax protein levels as well as telomerase activity may play an important role in its mechanism of action.
Liu
J J
JJ
Department of Hematology and Oncology, The Third Affiliated Hospital of Sun Yat-sen University, 510630 Guangzhou, Guangdong, P.R. China. jiajun.l@163.com
Huang
R W
RW
Lin
D J
DJ
Wu
X Y
XY
Peng
J
J
Pan
X L
XL
Song
Y Q
YQ
Lin
Q
Q
Hou
M
M
Wang
D N
DN
Chen
F
F
Zhang
M H
MH
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D045786:Diterpenes, Kaurane; D006801:Humans; D020014:K562 Cells / Q000187:drug effects* / Q000648:ultrastructure; D008854:Microscopy, Electron; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051028:bcl-2-Associated X Protein
D000970:Antineoplastic Agents; C494826:BAX protein, human; D004224:Diterpenes; D045786:Diterpenes, Kaurane; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C011959:oridonin; D019098:Telomerase