Aspirin Protects Caco2 Cells From Apoptosis After Serum Deprivation Through the Activation of a PI 3

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

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The PI-3K Pathway
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Inhibits
Cox1/2
Arachidonate/ Prostaglandins/ Leukotriens
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Effect of Aspirin Treatment on Apoptosis Induced
by Serum Deprivation in Caco-2 cells O
Fig. 01
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Effect of 2 5 mM Aspirin Treatment on Cell
Cycle Distribution Observed After Caco-2 cells
Serum Withdrawal O
Fig. 02
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Effect of 2 5 mM Aspirin Treatment on (Ser 437)
Phosphorylated AKT Total AKT
O
Fig. 03
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Effect of 2 5 mM AspirinTreatment on PI3-kinase
Activity in 96-h Serum-Starved Cells
O
Fig. 04
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Effect of 5 mM Aspirin Treatment on (Ser 437)
Phosphorylated AKT Total AKT phosphorylated
ERK1/2 Total ERK2
O
Fig. 05
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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
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Effect of PD98059 LY294002 Alone or in
Combination with Aspirin on Apoptosis During
Caco-2 Starvation
O
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Effect of Aspirin Vp-16 Treatments on the
phosphorylation Status of AKT Protein
O
Fig. 07
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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
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Effect of PD98059 LY94002 Treatments Alone or
in combination with Aspirin on Cell Cycle
Distribution During Caco-2 Starvation
O
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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.

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