Wogonin induces apoptosis by activation of ERK and p38 MAPKs signaling pathways and generation of reactive oxygen species in human breast cancer cells

被引:53
作者
Yu, Ji Sun [1 ]
Kim, An Keun [1 ]
机构
[1] Sookmyung Womens Univ, Coll Pharm, Biochem Lab, Seoul 140742, South Korea
关键词
apoptosis; breast cancer; mitogen-activated protein kinases; reactive oxygen species; wogonin; IN-VITRO; FLAVONOID WOGONIN; STRESS; DEATH; JNK; KINASES; RADIX; ROS;
D O I
10.1007/s10059-011-0041-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Wogonin is a one of the bioactive compounds of Scutellaria baicalensi Georgi which has been shown to have antiinflammatory, anticancer, antiviral and neuroprotective effects. However, the underlying mechanisms by which wogonin induces apoptosis in cancer cells still remain speculative. Here we investigated the potential activation of MAPKs and generation of reactive oxygen species (ROS) by wogonin on MCF-7 human breast cancer cells. These results showed that wogonin induced mitochondria and death-receptor-mediated apoptotic cell death, which was characterized by activation of several caspases, induction of PARP cleavage, change of antiapoptotic/proapoptotic Bcl-2 family member ratios and cleavage of Bid. We also found that generation of ROS was an important mediator in wogonin-induced apoptosis. Further investigation revealed that wogonin activated ERK and p38 MAPKs, which was inhibited by N-acetyl cysteine (NAC), a ROS scavenger, indicating that wogonin-induced ROS are associated with MAPKs activation. These data demonstrate that wogonin may be a novel anticancer agent for treatment of breast cancer.
引用
收藏
页码:327 / 335
页数:9
相关论文
共 39 条
[1]   Apoptosis induced in neuronal cells by oxidative stress: role played by caspases and intracellular calcium ions [J].
Annunziato, L ;
Amoroso, S ;
Pannaccione, A ;
Cataldi, M ;
Pignataro, G ;
D'Alessio, A ;
Sirabella, R ;
Secondo, A ;
Sibaud, L ;
Di Renzo, GF .
TOXICOLOGY LETTERS, 2003, 139 (2-3) :125-133
[2]   Protein-protein interactions and cancer: small molecules going in for the kill [J].
Arkin, M .
CURRENT OPINION IN CHEMICAL BIOLOGY, 2005, 9 (03) :317-324
[3]   ROS, stress-activated kinases and stress signaling in cancer [J].
Benhar, M ;
Engelberg, D ;
Levitzki, A .
EMBO REPORTS, 2002, 3 (05) :420-425
[4]   Wogonin, a bioactive flavonoid in herbal tea, inhibits inflammatory cyclooxygenase-2 gene expression in human lung epithelial cancer cells [J].
Chen, Lih-Geeng ;
Hung, Liang-Yi ;
Tsai, Kun-Wei ;
Pan, Ying-Shia ;
Tsai, Yi-Da ;
Li, Yi-Zhen ;
Liu, Yi-Wen .
MOLECULAR NUTRITION & FOOD RESEARCH, 2008, 52 (11) :1349-1357
[5]   Effects of wogonin, a plant flavone from Scutellaria radix, on skin inflammation:: in vivo regulation of inflammation-associated gene expression [J].
Chi, YS ;
Lim, H ;
Park, H ;
Kim, HP .
BIOCHEMICAL PHARMACOLOGY, 2003, 66 (07) :1271-1278
[6]   Anticancer effects of wogonin in both estrogen receptor-positive and -negative human breast cancer cell lines in vitro and in nude mice xenografts [J].
Chung, Heekyoung ;
Jung, Youn -Mi ;
Shin, Dong-Hui ;
Lee, Jeong-Yeon ;
Oh, Mi-Yun ;
Kim, Hyun-Jun ;
Jang, Ki Seok ;
Jeon, Su Jin ;
Sun, Kun Ho ;
Kong, Gu .
INTERNATIONAL JOURNAL OF CANCER, 2008, 122 (04) :816-822
[7]   Signal transduction by the JNK group of MAP kinases [J].
Davis, RJ .
CELL, 2000, 103 (02) :239-252
[8]   Wogonin prevents immunosuppressive action but not anti-inflammatory effect induced by glucocorticoid [J].
Enomoto, Riyo ;
Suzuki, Chie ;
Koshiba, Chika ;
Nishino, Takayuki ;
Nakayama, Mikiko ;
Hirano, Hiroyuki ;
Yokoi, Toshio ;
Lee, Eibai .
SIGNAL TRANSDUCTION PATHWAYS, PT C: CELL SIGNALING IN HEALTH AND DISEASE, 2007, 1095 :412-417
[9]   New insights on the anticancer properties of dietary polyphenols [J].
Fresco, P. ;
Borges, F. ;
Diniz, C. ;
Marques, M. P. M. .
MEDICINAL RESEARCH REVIEWS, 2006, 26 (06) :747-766
[10]   Targeting apoptosis pathways in cancer therapy [J].
Ghobrial, IM ;
Witzig, TE ;
Adjei, AA .
CA-A CANCER JOURNAL FOR CLINICIANS, 2005, 55 (03) :178-194