Neoalbaconol induces energy depletion and multiple cell death in cancer cells by targeting PDK1-PI3-K/Akt signaling pathway
文献类型：期刊论文
| 作者 | Deng, Q.1,2,3; Yu, X.1,2,3; Xiao, L.1,2,3; Hu, Z.1,2,3; Luo, X.1,2,3 ; Tao, Y.1,2,3; Yang, L.1,2,3,4; Liu, X.1,2,3; Chen, H.6; Ding, Z.5
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| 刊名 | CELL DEATH & DISEASE
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| 出版日期 | 2013-09-01 |
| 卷号 | 4页码:e804 |
| 关键词 | neoalbaconol PDK1 PI3-K/Akt energy depletion cancer cell death |
| ISSN号 | 2041-4889 |
| 通讯作者 | Liu, J (reprint author), Chinese Acad Sci, Kunming Inst Bot, 132 Heilongtan Lanhei Rd, Kunming 650204, Yunnan, Peoples R China.,jkliu@mail.kib.ac.cn ; ycao98@vip.sina.com |
| 英文摘要 | Many natural compounds derived from plants or microbes show promising potential for anticancer treatment, but few have been found to target energy-relevant regulators. In this study, we report that neoalbaconol (NA), a novel small-molecular compound isolated from the fungus, Albatrellus confluens, could target 3-phosphoinositide-dependent protein kinase 1 (PDK1) and inhibit its downstream phosphoinositide-3 kinase (PI3-K)/Akt-hexokinase 2 (HK2) pathway, which eventually resulted in energy depletion. By targeting PDK1, NA reduced the consumption of glucose and ATP generation, activated autophagy and caused apoptotic and necroptotic death of cancer cells through independent pathway. Necroptosis was remarkably induced, which was confirmed by several necroptosis-specific markers: the activation of autophagy, presence of necrotic morphology, increase of receptor-interacting protein 1 (RIP1)/RIP3 colocalization and interaction and rescued by necroptosis inhibitor necrostatin-1. The possibility that Akt overexpression reversed the NA-induced energy crisis confirmed the importance of the PDK1-Akt-energy pathway in NA-mediated cell death. Moreover, NA shows the capability to inhibit PI3-K/Akt signaling and suppress tumor growth in the nasopharyngeal carcinoma (NPC) nude mouse model. These results supported the feasibility of NA in anticancer treatments. |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 学科主题 | Cell Biology |
| 类目[WOS] | Cell Biology |
| 研究领域[WOS] | Cell Biology |
| 关键词[WOS] | NASOPHARYNGEAL CARCINOMA-CELLS ; PROTEIN-KINASE ; BIODIVERSITY HOTSPOTS ; INDUCED AUTOPHAGY ; SMALL-MOLECULE ; PDK1 ; ACTIVATION ; MECHANISMS ; LC3 ; TRANSDUCTION |
| 收录类别 | SCI |
| 资助信息 | National Basic Research Program of China [2009CB522300]; National Nature Science Foundation of China [90813028, 30830113]; Hunan Provincial Innovation Foundation for Postgraduate |
| 语种 | 英语 |
| WOS记录号 | WOS:000325370300021 |
| 公开日期 | 2013-11-12 |
| 源URL | [http://ir.kib.ac.cn/handle/151853/17282]  |
| 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.Cent S Univ, Canc Res Inst, Xiangya Sch Med, Changsha, Hunan, Peoples R China 2.Cent S Univ, Chinese Minist Educ, Key Lab, Changsha, Hunan, Peoples R China 3.Cent S Univ, Chinese Minist Publ Hlth, Key Lab Carcinogenesis, Changsha, Hunan, Peoples R China 4.Cent S Univ, Mol Imaging Ctr, Changsha, Hunan, Peoples R China 5.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650204, Yunnan, Peoples R China 6.Univ Minnesota, Hormel Inst, Austin, MN 55912 USA |
| 推荐引用方式 GB/T 7714 | Deng, Q.,Yu, X.,Xiao, L.,et al. Neoalbaconol induces energy depletion and multiple cell death in cancer cells by targeting PDK1-PI3-K/Akt signaling pathway[J]. CELL DEATH & DISEASE,2013,4:e804. |
| APA | Deng, Q..,Yu, X..,Xiao, L..,Hu, Z..,Luo, X..,...&Cao, Y..(2013).Neoalbaconol induces energy depletion and multiple cell death in cancer cells by targeting PDK1-PI3-K/Akt signaling pathway.CELL DEATH & DISEASE,4,e804. |
| MLA | Deng, Q.,et al."Neoalbaconol induces energy depletion and multiple cell death in cancer cells by targeting PDK1-PI3-K/Akt signaling pathway".CELL DEATH & DISEASE 4(2013):e804. |
入库方式： OAI收割
来源：昆明植物研究所
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