Trichothecin Induces Cell Death in NF-kappa B Constitutively Activated Human Cancer Cells via Inhibition of IKK beta Phosphorylation
文献类型：期刊论文
| 作者 | Su, Jia1,2; Zhao, Peiji1; Kong, Lingmei1,2; Li, Xingyao1,2; Yan, Juming1,2; Zeng, Ying1 ; Li, Yan1
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| 刊名 | PLOS ONE
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| 出版日期 | 2013-08-01 |
| 卷号 | 8期号:8页码:e71333 |
| 关键词 | COLITIS-ASSOCIATED CANCER MULTIPLE-MYELOMA CELLS P65 PHOSPHORYLATION ENDOPHYTIC FUNGUS KINASE-ACTIVITY TUMOR-GROWTH IN-VITRO PATHWAY APOPTOSIS INFLAMMATION |
| ISSN号 | 1932-6203 |
| 通讯作者 | Li, Y (reprint author), Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming, Peoples R China.,liyanb@mail.kib.ac.cn |
| 英文摘要 | 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. |
| WOS标题词 | Science & Technology |
| 学科主题 | Multidisciplinary Sciences |
| 类目[WOS] | Multidisciplinary Sciences |
| 研究领域[WOS] | Science & Technology - Other Topics |
| 关键词[WOS] | COLITIS-ASSOCIATED CANCER ; MULTIPLE-MYELOMA CELLS ; P65 PHOSPHORYLATION ; ENDOPHYTIC FUNGUS ; KINASE-ACTIVITY ; TUMOR-GROWTH ; IN-VITRO ; PATHWAY ; APOPTOSIS ; INFLAMMATION |
| 收录类别 | SCI |
| 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] |
| 语种 | 英语 |
| WOS记录号 | WOS:000324518400104 |
| 公开日期 | 2013-11-12 |
| 源URL | [http://ir.kib.ac.cn/handle/151853/17287]  |
| 专题 | 昆明植物研究所_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 |
| 推荐引用方式 GB/T 7714 | 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. |
入库方式： OAI收割
来源：昆明植物研究所
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