The Combination of Berberine and Irradiation Enhances Anti-Cancer Effects Via Activation of p38 MAPK Pathway and ROS Generation in Human Hepatoma Cells

被引:87
作者
Hur, Jung-Mu [2 ]
Hyun, Mee-Sun [3 ]
Lim, Sang-Yong
Lee, Woo-Yiel [4 ]
Kim, Dongho [1 ]
机构
[1] Korea Atom Energy Res Inst, Radiat Res Ctr Biotechnol, Adv Radiat Technol Inst, Chonbuk 580185, Jeongeup, South Korea
[2] Chong Kun Dang Healthcare Corp, Res Ctr, Chungnam 344827, Dangjin, South Korea
[3] Wonkwang Univ, Profess Grad Sch Oriental Med, Iksan, South Korea
[4] Konyang Univ, Dept Pharmaceut Engn, Nonsan 320711, South Korea
关键词
RADIATION; APOPTOSIS; BERBERINE; RADIOTHERAPY; ROS; p38; NITRIC-OXIDE SYNTHASE; CYTOCHROME-C RELEASE; DNA-DAMAGE; APOPTOSIS; EXPRESSION; DEATH; CHEMOTHERAPY; REQUIREMENT; INDUCTION; THERAPY;
D O I
10.1002/jcb.22198
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
Berberine, an isoquinoline plant alkaloid, has been known to generate a wide variety of biochemical and pharmacological effects. In order to elucidate the molecular mechanism for the berberine-induced enhancement of radio-sensitization, the human hepatoma HepG2 cells were treated with berberine combined with irradiation. The anti-tumor effect of gamma radiation was found to be significantly enhanced by berberine. The evidences of apoptosis, such as apoptotic DNA fragmentation and annexin V staining, were observed in the cells treated with the combination of berberine and irradiation. Additionally, the levels of reactive oxygen species (ROS) and nitric oxide (NO) were apparently elevated in the combination system. The activations of p38, Bax, and caspase-3 were also detected in the irradiated cells pretreated with berberine. The productions of ROS and annexin V staining in the cells treated with the combination of berberine and irradiation were significantly inhibited by the specific inhibitor of p38 MAPK, SB203580. The cell death induced by berberine alone or the combination of berberine and irradiation was suppressed by the anti-oxidant, N-acetyl cysteine (NAC). Taken together, the present results clearly indicate that the combination of berberine and gamma-radiation enhance the anti-cancer effects through the p38 MAPK pathway and ROS generation. J. Cell. Biochem. 107: 955-964, 2009. (C) 2009 Wiley-Liss, Inc.
引用
收藏
页码:955 / 964
页数:10
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