Chemistry Reference
In-Depth Information
supplemented and unsupplemented cells by dye exclusion staining. The
in vivo
protection factors
for NO
2
.
and
1
O
2
were 17.6 and 6.3, respectively, which compared to
in vitro
protection factors for
lycopene supplementation of only 8.2 and 3.1, respectively. These investigators suggested that the
difference might be due to lower lycopene uptake or lycopene molecule aggregation when lycopene
was added directly to cells (
in vitro
), but it could have been due to an uptake of phenolic compounds
and vitamin C by harvested lymphocytes exposed to the plasma of the tomato juice drinkers. Singlet
oxygen was quenched by energy transfer to the lycopene triplet state (highly subject to irrevers-
ible loss through oxidation) that reverts to the ground state, while the nitrogen dioxide radical was
quenched by electron transfer producing a lycopene radical cation. Unless terminated by ascorbate
or other antioxidant this radical was highly oxidizing to amino acids, such as tyrosine and cysteine,
unlike the
in vivo
situation, where adequate antioxidants are available in the cell. Lycopene radi-
cal quenching may not be as available under cell culture situations and may not mimic the
in vivo
prostate environment.
It has long been known that whether
-carotene acts as a pro-oxidant or an antioxidant,
depends upon its concentration and oxygen partial pressure (Burton and Ingold 1984). Cell cul-
ture experiments are usually performed at atmospheric oxygen partial pressures of 160 mmHg
(21% O
2
) whereas
in vivo
, tissues are dependent on oxygen diffusion rates and may be as low
as 30-70 mmHg (4%-10% O
2
) (Crawford and Blankenhorn 1991). At lower partial pressures,
β
β
-carotene and lycopene tend to act as antioxidants in both organic and aqueous phase systems
but some reports indicate that at atmospheric partial pressures (encountered in cell culture)
they may act as pro-oxidants (Edge and Truscott 1997). Lycopene concentration, cell type, the
presence of other antioxidants, and incubation environment probably all play a role in the pro-
oxidative or antioxidative nature of lycopene and must be kept in mind as we review lycopene
effects on cells in culture.
21.5.2 L
YCOPENE
AS
A
P
RO
-O
XIDANT
OR
A
NTIOXIDANT
IN
C
ELL
C
ULTURES
Whether lycopene is acting as a pro-oxidant or an antioxidant and under what circumstances is
a continuing issue. Investigators have measured the biomarkers of oxidative stress to explore this
question. The hexane extracts of tomato paste or lycopene decreased malondialdehyde (MDA)
adduct formation (a measure of lipid peroxide formation) at physiological lycopene concentrations
(0.1-1
M) in LNCaP cells incubated for 24 and 48 h. But MDA levels were increased in cells
incubated in 5 and 10
μ
M lycopene (Hwang and Bowen 2005a). DNA damage, measured as 8-OH
deoxyguanosine/guanosine ratio (8OHdG/dG), was also increased with 5
μ
μ
M lycopene and physi-
ologic concentrations were not protective of DNA except 1
μ
M lycopene at 48 h. However, LNCaP
cell growth inhibition of 55% was seen at 1
M lycopene (a concentration associated with lower
MDA and no change in DNA damage) indicating that the lycopene radical may not have been the
direct cause (Hwang and Bowen 2005a). Nevertheless, lycopene concentration and incubation time
are important variables in the ensuing discussion of lycopene effects on prostate cell function.
The pro-oxidative and antioxidative effects of lycopene have been explored in non-prostatic cell
lines. Yeh and Hu used foreskin i broblasts (Hs68 cells) with two different oxidation generators and
found that 20
μ
M lycopene acted as a lipid antioxidant in one system and a pro-oxidant in another
system, while DNA damage was not affected by the presence of either lycopene or
μ
β
-carotene (Yeh
and Hu 2000). When they incubated cells with 20 and 40
-carotene
(60°F for 1 h resulting in 80% and 35% loss of color, respectively) decreased cell viability was evi-
dent by 4 h and progressed dose-dependently, which was attributed to both apoptosis and cell lysis.
Unoxidized lycopene and
μ
M oxidized lycopene or
β
-carotene had no effect. Oxidized lycopene increased 8OHdG levels in
calf thymus DNA, and both 8OHdG and DNA chain breaks were increased in incubated i broblast
cells whereas the unoxidized carotenoids had no effect (Yeh and Hu 2001). A dose effect was also
noted by Lowe et al. using HT29 cells (colon carcinoma) where 1-3
β
μ
M lycopene suppressed DNA
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