Matrine upregulates the cell cycle protein E2F-1 and triggers apoptosis via the mitochondrial pathway in K562 cells.
Matrine is a major component of Sophora Flavescens and has been reported to stimulate differentiation of erythroleukemia cells. Here we show that matrine inhibits cell proliferation or induces apoptosis in a cell type-specific manner. The latter effect was investigated in more detail in the p53 deficient erythroleukemia cell line, K562. Matrine exposure induced apoptosis in a time- and dose-dependent manner in these cells. Interestingly, co-treatment with etoposide potentiated apoptosis. Further analysis of matrine-induced apoptotic changes revealed that E2F-1 and Apaf-1 were upregulated, whereas Rb was downregulated after 24 h of exposure. This was followed by Bax translocation, cytochrome c release, and caspase-9 and -3 activation. These results demonstrate that matrine triggers apoptosis of K562 cells primarily through the mitochondrial pathway and that matrine is a potential anti-tumor drug.
Jiang
Hua
H
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 YueYang Road, Shanghai 200031, China.
Hou
ChunHui
C
Zhang
ShuBing
S
Xie
HengYue
H
Zhou
WeiYing
W
Jin
QiHuang
Q
Cheng
XiaoDong
X
Qian
RuoLan
R
Zhang
XueJun
X
D000470:Alkaloids / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053477:Apoptotic Protease-Activating Factor 1 / Q000096:biosynthesis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D050687:E2F1 Transcription Factor / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism / Q000503:physiopathology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D011807:Quinolizines / Q000494:pharmacology*; D016160:Retinoblastoma Protein / Q000378:metabolism; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency; D020298:U937 Cells; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000093842:Matrines
C506592:APAF1 protein, human; D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D053477:Apoptotic Protease-Activating Factor 1; C494826:BAX protein, human; D050687:E2F1 Transcription Factor; D011807:Quinolizines; D016160:Retinoblastoma Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D005047:Etoposide; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9; D000093842:Matrines