2. Aspirin Protects Caco-2 Cells From Apoptosis After Serum Deprivation Through the Activation of a PI 3- Kinase/AKT/p21Cip/WAF1Pathway

3. P. Ricchi et al, Molecular Pharmacology, 64, 2003 Ashim Malhotra November 11, 2003 Cell Signaling

4. PLA2 PL PLA2 = Phospholipase A2 COX1/2 = cyThromboxanes LKT = Leukotrienes PLA2 = Phospholipase A2 COX1/2 = cyThromboxanes LKT = Leukotrienes COX 1/2 PGE2/ TXA2/ LKTs Cell Membrane A

5. The PI-3K Pathway

6. Inhibits Cox1/2 Arachidonate/ Prostaglandins/ Leukotriens

7. Effect of Aspirin Treatment on Apoptosis Induced by Serum Deprivation in Caco-2 cells ~O~ Fig. 01

8. Effect of 2 & 5 mM Aspirin Treatment on Cell Cycle Distribution Observed After Caco-2 cells Serum Withdrawal ~O~ Fig. 02

9. Effect of 2 & 5 mM Aspirin Treatment on (Ser 437) Phosphorylated AKT & Total AKT ~O~ Fig. 03

10. Effect of 2 & 5 mM AspirinTreatment on PI3- kinase Activity in 96-h Serum-Starved Cells ~O~~O~~O~~O~ Fig. 04

11. Effect of 5 mM Aspirin Treatment on (Ser 437) Phosphorylated AKT & Total AKT & phosphorylated ERK1/2 & Total ERK2 ~O~ Fig. 05

12. Effect of PD98059 & LY294002 Treatments Alone & in Combination with Aspirin on (Ser 437) phosphorylated AKT & Total AKT & phosphorylated ERK1/2 & Total ERK2 Expression ~O~~O~~O~~O~ Fig. 06

13. Effect of PD98059 & LY294002 Alone or in Combination with Aspirin on Apoptosis During Caco-2 Starvation ~O~~O~~O~~O~

14. Effect of Aspirin & Vp-16 Treatments on the phosphorylation Status of AKT Protein ~O~~O~~O~~O~ Fig. 07

15. Effect of 40 µM PD98059 or 50 µM LY294002 Treatments Alone or in combination with 2 & 5 mM Aspirin on p21 Cip/WAF1 & -Tubulin Expression in Serum- Starved Cells ~O~~O~~O~~O~ Fig. 08

16. Effect of PD98059 & LY94002 Treatments Alone or in combination with Aspirin on Cell Cycle Distribution During Caco-2 Starvation ~O~~O~~O~~O~

17. ConclusionsConclusionsConclusionsConclusions Aspirin treatment in Caco-2 cells interferes with serum deprivation induced apoptosis through PI –kinase & ERK kinase pathways. PI-3 kinase mediates survival effect of aspirin. Aspirin prevents an increase in the G2 cell cycle stage cells & dose dependently increases p21 expression. ~O~~O~~O~~O~

18. 4 presentations!! Phew!! AND now It is THE END!!!!!