Chemistry Reference
In-Depth Information
foci may progress concurrently and at a different rate to give rise to multiple primary
tumors, makes the colon a peculiarly suitable target organ for any given chemopre-
vention study. Indeed, chemoprevention of colorectal cancer in humans has been
the focus of a number of studies where fibers, vitamins, calcium, low fat, and non-
steroidal antiinflammatory drugs have all been shown to affect the incidence of this
disease (Duris et al., 1996; Langman and Boyle, 1999; Reddy, 1999). Approximately
70 percent of colorectal cancer is associated with environmental factors, probably
mainly the diet (Saikali et al., 2004). Thus, much attention has focused on decreas-
ing cancer risk through diet alterations, particularly consumption of probiotics and
increasing intake of dietary fiber (prebiotics). The term
probiotics
is defined as “a
viable microbial dietary supplement which beneficially affects the host through its
effects on the intestinal tract” (Gibson and Roberfroid, 1995). A prebiotic is defined
as a “indigestible food ingredient which beneficially affects the host by selectively
stimulating the growth and/or activating the metabolism of one or a limited number
of health promoting bacteria in the intestinal tract, thus improving the host's intes-
tinal balance” (Gibson and Roberfroid, 1995). It has been reported that ingestion of
probiotics, prebiotics, or combinations of both (synbiotics) plays an important role in
the prevention of colorectal cancer, and represents a novel new therapeutic option.
Probiotics and prebiotics act to alter the intestinal microflora by increasing concen-
trations of beneficial bacteria, such as lactobacilli and bifidobacteria, and reducing
the levels of pathogenic microorganisms. Probiotics and prebiotics may regulate col-
orectal cancer by the following possible mechanisms (Figure 14.2):
1. Changes in the colon pH
2. Alteration of gut xenobiotic metabolism
3. Modulation of immune system
4. Antioxidant property
5. Demutagenic effect
Lactobacilli and bifidobacteria are the two well-known probiotics that
could lower the risks of colon cancer and may act as most potent chemopreven-
tive organisms. Goldin and Gorbach have demonstrated that dietary administra-
tion of some specific lactobacilli strains significantly decreased the incidence of
1,2-dimethylhydrazine-induced experimental colon cancer (Goldin and Gorbacj,
1980; Goldin et al., 1996). Although the first set of strategies for cancer control is
ideally the removal of causative agents, such an approach remains very elusive for
colorectal malignancies, as yet. Several studies have suggested that the effect of diet
on cancer development is indirect, primarily by affecting the ability of the host to
metabolize procarcinogens to proximate carcinogens whose activation, in the case
of colon cancer, may be mediated by the bacterial flora in the large bowel. A number
of bacterial enzymes have been implicated in producing or enhancing mutagens,
carcinogens, and various tumor promoters, such as β-glucuronidase, azoreducatse,
7-α-hydroxy-steroid dehydrogenase, glycocholic acid hydrolase, and cholesterol
dehydrogenase (Goldin and Gorbach, 1976). Indeed, a number of studies have pro-
vided strong evidence in favor of a key role played by certain resident gut bacteria
