Lycopene Oxidation, Uptake, and Activity in Human Prostate Cell Cultures - Carotenoids: Physical, Chemical, and Biological Functions and Properties - page 438

useful in differentiating the effects of lycopene versus the mixture of biologically active compounds
in tomatoes as well as the exploration of plausible mechanisms of action. Cell culture studies have the
advantage of exploring the modulation of cellular processes in single cell types using known concentra-
tions of lycopene and can be used to evaluate possible synergies between other tomato constituents, such
as polyphenolic compounds, other carotenoids, and vitamin E. In order to fully appreciate the results
of cell culture studies using lycopene alone or lycopene in combination with other biologically active
compounds, it is important to understand (1) prostate biology, (2) the role of the various cells in prostate
function, (3) which cells are the most vulnerable to the carcinogenic process and how that process pro-
ceeds, and (4) the origin of each of the prostatic cell lines that has been used and its characteristics.
In cell culture, lycopene is a highly oxidizable nonpolar hydrocarbon supplied in an aqueous
medium and is incubated at body temperature for 12-72 h. The amount of intact lycopene or its
oxidation products delivered to and absorbed by various cell types is an important factor to keep in
mind when evaluating the effects of lycopene on various cellular processes. Before reviewing cell
culture studies designed to characterize the effects of lycopene on prostate cell biology, the charac-
teristics of prominent prostate cell lines, and the stability and uptake of lycopene by various prostate
cell lines are reviewed.

21.2 PROSTATE CELL BIOLOGY AND CARCINOGENESIS

21.2.1 T HE N ORMAL P ROSTATE
It is important to understand the architecture of the normal prostate and the complicated cross talk
between the heterogeneous cell types involved in the carcinogenic process in order to interpret the
effect of lycopene on various prostate cell lines in tissue culture. The prostate is mainly a secretory
organ that supplies 10%-30% of the seminal l uid for ejaculation. Figure 21.1 shows a micrograph
of normal prostate tissue. The peripheral zone (Sampson et al. 2007), where 70% of tumors can be
found, is marked by acinar (glands) that collect the l uid secreted by the surrounding secretory epi-
thelial cells. The secreted l uid is alkaline and is a complex mixture containing PSA, prostate acid
phosphatase (PAP), and prostasomes (Sampson et al. 2007) among other constituents. Prostasomes
are exocytosed from the acinar epithelial cells as small vesicles (40-500 nm) surrounded by a cho-
lesterol/sphingomyelin-rich membrane and contain numerous enzymes, immunosuppressants, zinc,
calcium, selenium, ATP, and neuroendocrine markers, such as neuropeptide Y. They promote sperm
viability and mobility (Kravets et al. 2000). Beneath the epithelial cells surrounding the acinar is a
layer of basal cells backed by stromal i broblasts and smooth muscle cells, which compose most of
the prostate structure. The basal cells do not secrete PSA or PAP, have few androgen receptors, but
develop these as they differentiate and move to the surface of the acinar (Miki and Rhim 2007). In
summary, the prostate is composed of many different cell types: cells found in the epithelium (stem
cells, transit-amplifying cells, basal cells, secretory cells, and neuroendocrine cells) and cells found in

FIGURE 21.1 (See color insert following page 336.) Normal tissue from human prostate showing secre-
tory section—hematoxilin and eosin staining showing epithelial cells lining secretory ducts backed by basal
and stromal cells. (Courtesy of A. Brollo, Wikimedia Commons, 2005.)