Fig. 10.

Schematic outline of the proposed action of ITPP on HIFs regulation. 1 ITPP regulates angiogenesis by activating PTEN that inhibits PI3K action, AkT phosphorylation and mTOR actitivy towards HIF at the endothelial cell level. This regulates the vessels and increases the blood flow, while 2 hypoxia mediated O₂ delivery by ITPP, allosteric effector of hemoglobin [15–18], increases the intra tumor pO₂, which also acts to destabilize HIF1α and down regulates VEGFs and VEGFs-related gene cascade. This directly reduces the endothelial cell mobilization, activation and growth, thus regulating the tumor VEGF-mediated pathological angiogenesis