Trichothecin Induces Cell Death in NF-kappa B Constitutively Activated Human Cancer Cells via Inhibition of IKK beta Phosphorylation
Su, Jia1,2; Zhao, Peiji1; Kong, Lingmei1,2; Li, Xingyao1,2; Yan, Juming1,2; Zeng, Ying1; Li, Yan1
2013-08-01
发表期刊PLOS ONE
ISSN1932-6203
卷号8期号:8页码:e71333
摘要Constitutive activation of the transcription factor nuclear factor-kappa B (NF-kappa B) is involved in tumorigenesis and chemoresistance. As the key regulator of NF-kappa B, IKK beta is a major therapeutic target for various cancers. Trichothecin (TCN) is a metabolite isolated from an endophytic fungus of the herbal plant Maytenus hookeri Loes. In this study, we evaluated the anti-tumor activity of TCN and found that TCN markedly inhibits the growth of cancer cells with constitutively activated NF kappa B. TCN induces G0/G1 cell cycle arrest and apoptosis in cancer cells, activating pro-apoptotic proteins, including caspase-3, -8 and PARP-1, and decreasing the expression of anti-apoptotic proteins Bcl-2, Bcl-xL, and survivin. Reporter activity assay and target genes expression analysis illustrated that TCN works as a potent inhibitor of the NF-kappa B signaling pathway. TCN inhibits the phosphorylation and degradation of IkB alpha and blocks the nuclear translocation of p65, and thus inhibits the expression of NF-kappa B target genes XIAP, cyclin D1, and Bcl-xL. Though TCN does not directly interfere with IKK beta kinase, it suppresses the phosphorylation of IKK beta. Overexpression of constitutively activated IKK beta aborted TCN induced cancer cell apoptosis, whereas knockdown of endogenous IKK beta with siRNA sensitized cancer cells toward apoptosis induced by TCN. Moreover, TCN showed a markedly weaker effect on normal cells. These findings suggest that TCN may be a potential therapeutic candidate for cancer treatment, targeting NF-kappa B signaling.
关键词Colitis-associated Cancer Multiple-myeloma Cells P65 Phosphorylation Endophytic Fungus Kinase-activity Tumor-growth In-vitro Pathway Apoptosis Inflammation
资助信息Chinese Academy of Sciences; Major State Basic Research Development Program of China [2009CB522300]; Natural Science Foundation of China [81173076]; Recruited Top Talent of Sciences and Technology of Yunnan Province [2009CI120]
学科领域Multidisciplinary Sciences
收录类别SCI
语种英语
WOS研究方向Science & Technology - Other Topics
WOS类目Multidisciplinary Sciences
WOS记录号WOS:000324518400104
引用统计
被引频次:9[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/17287
专题植物化学与西部植物资源持续利用国家重点实验室
作者单位1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
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Su, Jia,Zhao, Peiji,Kong, Lingmei,et al. Trichothecin Induces Cell Death in NF-kappa B Constitutively Activated Human Cancer Cells via Inhibition of IKK beta Phosphorylation[J]. PLOS ONE,2013,8(8):e71333.
APA Su, Jia.,Zhao, Peiji.,Kong, Lingmei.,Li, Xingyao.,Yan, Juming.,...&Li, Yan.(2013).Trichothecin Induces Cell Death in NF-kappa B Constitutively Activated Human Cancer Cells via Inhibition of IKK beta Phosphorylation.PLOS ONE,8(8),e71333.
MLA Su, Jia,et al."Trichothecin Induces Cell Death in NF-kappa B Constitutively Activated Human Cancer Cells via Inhibition of IKK beta Phosphorylation".PLOS ONE 8.8(2013):e71333.
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