J Agric Food Chem 2011,
PMID: 21314123
Chao, A-Ching; Hsu, Ya-Ling; Liu, Ching-Kuan; Kuo, Po-Lin
This study is the first to investigate the anticancer effects of α-mangostin in human glioblastoma cells. α-Mangostin decreases cell viability by inducing autophagic cell death but not apoptosis. Pretreatment of cells with the autophagy inhibitors 3-methyladenine (3-MA) and bafilomycin or knockdown beclin-1, resulted in the suppression of α-mangostin-mediated cell death. We also found that liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) signaling is a critical mediator of α-mangostin-induced inhibition of cell growth. Activation of AMPK induces α-mangostin-mediated phosphorylation of raptor, which subsequently associates with 14-3-3γ and results in the loss of mTORC1 activity. The phosphorylation of both downstream targets of mTORC1, p70 ribosomal protein S6 kinase (p70S6 kinase) and 4E-BP1, is also diminished by activation of AMPK. Furthermore, the inhibition of AMPK expression with shRNAs or an inhibitor of AMPK reduced α-mangostin-induced autophagy and raptor phosphorylation, supporting the theory that activation of AMPK is beneficial to autophagy. A further investigation revealed that α-mangostin also induced autophagic cell death in transplanted glioblastoma in nude mice. Together, these results suggest a critical role for AMPK activation in the α-mangostin-induced autophagy of human glioblastoma cells.
Diseases/Pathways annotated by Medline MESH: Glioblastoma
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Text Mining Data
mTORC1 ⊣ AMPK: "
Activation of
AMPK induces a-mangostin mediated phosphorylation of raptor, which subsequently associates with 14-3-3? and
results in the loss of
mTORC1 activity
"
AMPK → raptor: "
Activation of AMPK induces a-mangostin mediated phosphorylation of raptor , which subsequently associates with 14-3-3? and results in the loss of mTORC1 activity
"
raptor → AMPK: "
Furthermore, the inhibition of AMPK expression with shRNAs or an inhibitor of AMPK reduced a-mangostin induced autophagy and raptor phosphorylation, supporting the theory that activation of AMPK is beneficial to autophagy
"
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