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Aspirin Protects Caco-2 Cells From Apoptosis After Serum Deprivation Through the Activation of a PI 3-Kinase/AKT/p21

Aspirin Protects Caco-2 Cells From Apoptosis After Serum Deprivation Through the Activation of a PI 3-Kinase/AKT/p21 Cip / WAF 1 Pathway . P. Ricchi et al, Molecular Pharmacology , 64 , 2003. Ashim Malhotra November 11, 2003 Cell Signaling. PL. A. Cell Membrane.

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Aspirin Protects Caco-2 Cells From Apoptosis After Serum Deprivation Through the Activation of a PI 3-Kinase/AKT/p21

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

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

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

  4. The PI-3K Pathway

  5. Inhibits Cox1/2 Arachidonate/ Prostaglandins/ Leukotriens

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

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

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

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

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

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

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

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

  14. Effect of 40 µM PD98059 or 50 µM LY294002 Treatments Alone or in combination with 2 & 5 mM Aspirin on p21Cip/WAF1 & -Tubulin Expression in Serum-Starved Cells ~O~ Fig. 08

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

  16. Conclusions ~O~ • 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.

  17. 4 presentations!! Phew!! AND now It is THE END!!!!!

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