Effects of Qu on cell cycle. Qu is able to regulate cell cycle by directly binding several molecular targets and, depending on the cell type and tumor origin, it blocks the cell cycle at G2/M or at the G1/S transition. At the G1/S transition, Qu blocks cell-cycle progression through the up-regulation of p21 and p27 and p53. p21 exerts an inhibitory activity on several CDKs. In particular, p21 inhibits CDK2-cyclin E, with the consequent inhibition of CDK2-dependent phosphorylation of pRb and the sequestration of E2F1, thus inhibiting gene transcription induced by E2F1 and progression into and through S phase. p21 also inhibits CDK2-cyclin A and CDK1-cyclin B, which are essential for progression through S phase and G2, respectively. p27 exerts several effects on cell cycle, but only under certain conditions it can inhibit the complexes CDK4-cyclin D and CDK6-cyclin D. The tumor suppressor p53, once activated, can induce several different cellular responses, including growth arrest and apoptosis. Growth arrest is essentially elicited through the up-regulation of the genes that encode for inhibitors of cell-cycle progression, including p21 and p27. In different cellular models, Qu stabilizes p53 both at mRNA and protein levels. Apart from blocking cell growth through the direct action on key modulators of cell cycle, Qu is able to induce apoptosis via mitochondrial pathway: indeed, Qu can disrupt MMP, which in turn provokes the release of cytochrome c in the cytoplasm, a phenomenon that activates multiple caspases, such as caspase-3 and -7.
