AJDW, polysaccharide from Albizia julibrissin, binds to PI3K and induces cell cycle arrest and ROS-mediated pancreatic cancer cell apoptosis

To understand the material basis of the extraction from Albizia julibrissin , a traditional oriental medicine that has reported antitumor activity, a novel neutral polysaccharide fraction and its anti-pancreatic cancer activity were identified in this study. Combined with the monosaccharide composition detection and methylation, this polysaccharide, named AJDW, is proven to contain mannose: glucose: galactose: xylose: arabinose with a molar ratio of 7.36: 9.03: 7.06: 2.24: 1; moreover, 1,4,6-Glc p and 1,4-Man p are found to be the most abundant residues in AJDW. In vitro and in vivo bioactivity tests shows that AJDW may significantly inhibit the proliferation of pancreatic cancer cells and effectively impede the growth of patient-derived xenografts in mouse model. Mechanism studies reveal that AJDW suppresses pancreatic cancer migration, blocks the cell cycle in the S phase, and induces ROS-mediated apoptosis by reducing mitochondrial membrane potential. Further study show that AJDW binds to PI3K and inactivate the phosphorylation of the PI3K/Akt/mTOR signaling pathway in pancreatic cancer cells. In summary, the results suggest that AJDW is an active anti-tumor component in the extraction of Albizia julibrissin and could function as a potential anti-tumor leading compound for new drug development.