α-mangostin is an inhibitor of PI3K/AKT with IC50 value of 32 μM (pancreatic cancer cell hTERT-HPNE for 48 hours) [1].
PI3K (phosphatidylinositol-3 kinases) is a member of lipid kinase family and has serine / threonine (Ser/Thr) kinase activity. Akt plays an important role in modulating the function of numerous substrates involved in the regulation of cell survival, cell cycle progression and cellular growth. Recently, it has been shown that PI3K/Akt signaling pathway components are frequently oveexpressed in a variety of human cancers [1] [2].
α-mangostin is a potent FAS inhibitor. When pancreatic cancer cell line BxPc-3, α-mangostin treatment suppressed the cell viability and EMT process via suppressing the activation of PI3K/AKT pathway[1].
In BALb/c nude mice model with BxPc-3 cells xenograft, administration ofα-mangostin (50 or 100 mg.kg) dramatically inhibited tumor growth with a dose-dependent manner [1].
It is also reported thatα-mangostin could target other signaling pathway. In breast cancer cell line, α-mangostin suppressed FAS expression and inhibited intracellular FAS activity that resulted in the cells apoptosis [3]. When tested with breast cancer cell line MCF-7, α-mangostin promoted cell apoptosis via regulating NF-κB, Bax/Bcl-2 and heat shock protein 70 [4].
References:
[1].?? ?Xu, Q., et al., alpha-Mangostin suppresses the viability and epithelial-mesenchymal transition of pancreatic cancer cells by downregulating the PI3K/Akt pathway. Biomed Res Int, 2014. 2014: p. 546353.
[2].?? ?Carnero, A. and J.M. Paramio, The PTEN/PI3K/AKT Pathway in vivo, Cancer Mouse Models. Front Oncol, 2014. 4: p. 252.
[3].?? ?Li, P., W. Tian, and X. Ma, Alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis in breast cancer cells. Mol Cancer, 2014. 13: p. 138.
[4].?? ?Ibrahim, M.Y., et al., alpha-Mangostin from Cratoxylum arborescens demonstrates apoptogenesis in MCF-7 with regulation of NF-kappaB and Hsp70 protein modulation in vitro, and tumor reduction in vivo. Drug Des Devel Ther, 2014. 8: p. 1629-47.