Novel Chemically Synthesized, Alpha-Mangostin-Loaded Nano-Particles, Enhanced Cell Death Through Multiple Pathways Against Malignant Glioma

Mangostin is a hydrophobic agent with potential anticancer activity. Molecular dynamics computer simulation indicated methoxy poly(ethylene glycol)-poly(lactide) (MPEG-PLA) and α-mangostin (α-M) have good compatibility. The α-M-loaded nano-particles acting as an anticancer agents against growth of glioma cells were prepared by self-assembly methods. In this study, the effects of α-M-loaded nano-particles, α-M/MPEG-PLA with drug loading of 15% and a mean particle size of 32 nm, on the growth of glioma cells were examined both in vitro and in vivo. The occurrence of changes in the cell signaling molecules and expression levels of various proteins related to cell death and glioma xenograft models (i.e., zebra fish, subcutaneous-mouse and orthotopic-mouse) growth following the administration of α-M/MPEG-PLA were investigated. The novel α-M/MPEG-PLA inhibited the growth of malignant glioma cells, induced cells apoptosis with cleaved caspases expression and DNA fragmentation, along with down-regulation of anti-apoptotic molecules and up-regulation of apoptotic molecules. Furthermore, decreased proliferation as well as vascularization of the tumor in vivo models were significantly achieved. A dramatic induction of programmed cell death was found in malignant glioma cells after treatment with synthetic α-M/MPEG-PLA. These results suggest that synthetic α-M/MPEG-PLA could be a promising novel anticancer agent for performing chemotherapy against malignant glioma.