Figure 8

Schematic diagram of the hypothetical molecular signaling pathways of the expression of p27 by which moderate increase in the concentration of D -(+)-glucose down-regulates and deficiency of D -(+)-glucose or L -leucine up-regulates the expression of p27. This summary diagram shows the outline of how 4-hydroxytamoxifen uses primarily pathway #1 to up-regulate the expression of p27, arrest the G1-to-S phase transition of cell cycle, and inhibit DNA replication in human breast cancer cells in vitro. 4-Hydroxytamoxifen preferentially phosphorylates 4E-BP1 over S6K1. The diagram also shows the outline of how the deficiency of D-(+)-glucose uses primarily pathway #2 to up-regulate the expression of p27, arrest the G1-to-S phase transition of cell cycle, and inhibit DNA replication in human breast cancer cells in vitro. D-(+)-Glucose deficiency preferentially phosphorylates S6K1 over 4E-BP1. The diagram also shows that the deficiency of L-leucine enters the pathway #2 at points different from the deficiency of D-(+)-glucose. Finally, the diagram shows that deficiency of D-(+)-glucose or L-leucine uses L-upstream molecular signaling pathway #2 of the expression of p27 to up-regulate the phosphorylation of AMPK and the expression of mitochondrial ATP5A and SIRT3. The mitochondrial SIRT3 exerts anti-aging and other metabolic effects on the cells.