Dietary whey proteins and oxidative stress in the prostate

1
Dietary whey proteins and oxidative stress in the
prostate

• Kyle D. Kent. J. Bomser and W. J. Harper
• Department of Food Science and Technology
• The Ohio State University

2
The prostate

• Prostate cancer is the 2nd leading cause of
  cancer death in men
• Oxidative stress is a major contributor
• Diets rich in antioxidants may prevent cancer
  development

3
Cancer development
mutation
glutathione
oxidative stress
4
What is glutathione (GSH)?

• The major cellular antioxidant
• Composed of 3 amino acids
• glutamate, cysteine, glycine
• GSH synthesis is limited by cysteine availability
• GSH protects against oxidant-induced cell damage

5
Why Whey?

• Cystine-rich protein source
• Whey proteins
• a-lactalbumin (4 cystine per molecule)
• ß-lactoglobulin (2 cystine per molecule)
• bovine serum albumin (17 cystine per molecule)

6
Hypothesis

• Digested whey protein isolate can elevate
  intracellular GSH and protect against
  oxidant-induced cell death in
• human prostate cells

7
The objectives of the study were

• To determine if digested whey protein isolate
  (WPI) can elevate GSH in human prostate
  epithelial cells
• To determine if digested WPI protects against
  oxidant-induced cell death in human prostate
  epithelial cells

8
SDS-PAGE of WPI
(A) undigested WPI (B) digested WPI (C)
a-lactalbumin (D) ß-lactoglobulin (E) bovine
serum albumin
9
Objective 1 Can digested WPI elevate
intracellular GSH in human prostate cells?
10
Materials

• Human prostate epithelial cells (RWPE-1)
• Digested whey protein isolate (d-WPI)
• Digested sodium caseinate (d-casein)
• N-acetylcysteine (NAC)
• Buthionine sulfoximine (BSO)

11
Concentration and time dependent GSH elevation
d-WPI
significant difference from the control
(plt0.05).
12
Cysteine availability and GSH concentration
significant difference from the control
(plt0.05).
13
Inhibition of GSH synthesis by BSO
significant difference from the control
(plt0.05).
14
Objective 2 Can digested WPI protect human
prostate cells against oxidant-induced cell death?
15
Materials

• Human prostate epithelial cells (RWPE-1)
• Digested whey protein isolate (d-WPI)
• 500 µg/mL, 24 hrs
• Buthionine sulfoximine (BSO)
• 500 µM, 24 hrs
• t-butyl hydroperoxide (TBHP)
• 0-1000 µM, 24 hrs

16
Protection vs. TBHP-induced cell death


Significant difference from the control at each
concentration of TBHP (plt0.05).
17
Conclusions

• Digested WPI elevates intracellular GSH of human
  prostate cells
• Elevation of intracellular GSH by de novo
  synthesis
• Digested WPI also protects against
  oxidant-induced cell death

18
Acknowledgments

• Joshua A. Bomser
• W. James Harper
• Institute of Food Technologists
• The Ohio State University Department of Food
  Science Technology