Neoalbaconol induces energy depletion and multiple cell death in cancer cells by targeting PDK1-PI3-K/Akt signaling pathway

	Neoalbaconol induces energy depletion and multiple cell death in cancer cells by targeting PDK1-PI3-K/Akt signaling pathway
	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; Feng, T.5; Tang, Y.1,2,3; Weng, X.1,2,3; Gao, J.1,2,3; Yi, W.1,2,3; Bode, A. M.6; Dong, Z.6; Liu, J.5 ; Cao, Y.1,2,3,4
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
	2013-09-01
发表期刊	CELL DEATH & DISEASE
ISSN	2041-4889
卷号	4 页码:e804
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.
关键词	Neoalbaconol Pdk1 Pi3-k/akt Energy Depletion Cancer Cell Death
学科领域	Cell Biology
收录类别	SCI
语种	英语
WOS记录号	WOS:000325370300021
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/17282
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.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.

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