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
Corresponding AuthorLiu, 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
Source PublicationCELL DEATH & DISEASE
ISSN2041-4889
Volume4Pages:e804
AbstractMany 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.
KeywordNeoalbaconol Pdk1 Pi3-k/akt Energy Depletion Cancer Cell Death
Subject AreaCell Biology
Indexed BySCI
Language英语
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000325370300021
Citation statistics
Cited Times:26[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/17282
Collection植物化学与西部植物资源持续利用国家重点实验室
Affiliation1.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
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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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