Lycopene Oxidation, Uptake, and Activity in Human Prostate Cell Cultures - Carotenoids: Physical, Chemical, and Biological Functions and Properties - page 452

TABLE 21.3 Lycopene Effects on Prostate Cell IGF Signaling

Measurement and
Methods Reference Cell Type Lycopene Treatment Solvent Incubation Outcome

Liu et al.
(2008)

(1)Normal prostate
stromal cells (PrSC);
(2) 6S stromal
i broblasts prostate,
cancer-derived; (3)
NPE (PREC) primary
prostate epithelial
cells lacking androgen
receptor: Also as
cocultures

0.3-1 μ M lycopene THF 72 h followed by

24 h of CM
Cocultures of
(1) NPE +
PRSC or (2)
NPE + 6s cells
+ camptothecin
(CM)
IGF-1(0.15 or
1 ng/mL)
stimulated
NPE-6s
cocultures
w/wo 1 μM
lycopene

DNA fragmentation DHT(dihydrotestosterone) inhibited DNA

fragmentation of NPE cells induced by
CM when cocultured with 6s cells, but not
when cocultured with PrSC cells.
Lycopene at 1 μM in the NPE-6s
cocultures treated with CM or CM + DHT
overcame the antiapoptotic effect of DHT.
DHT increases IGF-1 mRNA sixfold and
lycopene decreased this DHT induction by
50% but had no effect on non-induced
IGF-1 mRNA; IGF-1 not induced by DHT
in PRSC cells

Androgen receptor (AR)
and β-catenin expression

24 h lycopene incubation reduced
DHT-induced AR expression by 70% and
AR nuclear localization by 60% in 6s cells

Cell viability by MTT
using 0.15 ng/mL IGF-1
(amount secreted by 6s
cell with DHT induction

NPE or PrEC monocultures: IGF-1
increased, CM reduced (NPE), lycopene
reduced viability with IGF-1 stimulation
but had no effect without it.

Lycopene decreased Akt phosphorylation
70% and completely prevented IGF-1
induced increase in GSK3
phosphorylation. IGF-1 decreased but
lycopene + IGF-1 rectii ed tyrosine
phosphorylation in GSK3.

1 μM lycopene 16 h
pretreatment with
immunoblots for Akt
and GSK3
phosphorylation at 0 and
4 h after IGF-1
stimulation

Note: THF = tetrahydrofuran; BHT = butylated hydroxytoluene, an antioxidant; Camptothecin (CM) = causes inhibition of the DNA enzyme topoisomerase (Top 1) which induces DNA
damage and apoptosis; DHT = dihydrotestosterone; PrEC = normal prostate stromal cells; LNCaP, PC-3, DU-145 = neoplastic prostate epithelial cells (See Table 21.1).