Genistein suppresses tumor necrosis factor-alpha-induced proliferation via the apoptotic signaling pathway in human aortic smooth muscle cells.
The proliferation of vascular smooth muscle cells (VSMCs) plays a key role in the development of atherosclerosis. Abnormal VSMC proliferation induces vascular dysfunction and several other pathological processes. The present study investigated the apoptotic effects of genistein on tumor necrosis factor-alpha (TNF-alpha)-induced proliferation in human aortic smooth muscle cells (HASMCs). The apoptotic effects of genistein were assessed to determine the mechanism(s) of its antiproliferative activity, including MTT, LDH assay, morphological change of cell, DNA fragmentation, and expression levels of pro- or anti-apoptotic molecules by RT-PCR and Western blots. The results show that genistein significantly reduced cell proliferation in TNF-alpha-induced HASMCs. Genistein also reduced intracellular nuclei staining with DAPI in a dose-dependent manner. In addition, genistein increased nucleosomal DNA fragmentation, increased the expression levels of Bax and c-Myc, and decreased the expression levels of Bcl-2 and Bcl-xL in TNF-alpha-induced HASMCs. Taken together, these findings indicate that genistein regulates the activation of apoptosis-related molecules in TNF-alpha-induced HASMCs, leading to the suppression of proliferation and induction of apoptosis.
Kim
Hyuck
H
Cardiovascular Medical Research Center, College of Korean Medicine, Dongguk University, Sukjang-Dong 707, Gyeongju 780-714, South Korea.
Lee
Min-Ja
MJ
Kim
Jai-Eun
JE
Park
Sun-Dong
SD
Moon
Hyung-In
HI
Park
Won-Hwan
WH
D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D019833:Genistein