Diet and cancer
- From: Taka <taka0038@xxxxxxxxx>
- Date: Fri, 20 Jun 2008 09:41:57 -0700 (PDT)
Recently I got the following e-mail:
Hi
I was browsing the sci.med.nutrition newsgroups and I noticed that you
have
posted quite a few messages and also that you seem to be knowledgeable
in
areas of biology.
I wanted to ask if you don't mind whether you believe diet and
metabolic
management can have an impact on managing cancer, extending survival
or
possibly even invoking a remission.
Specifically do you think that it is possible to balance nutrients,
easy to
obtain drugs and phytochemicals with a view to try to make it harder
for
cancer cells to grow, spread and mutate? ...say by trying to influence
metabolic and cell signaling pathways among other things?
I would like to know your ideas.
Thanks
Kaptan
and here is my answer:
Of course I believe diet plays a major role in cancer development and
prevention. After you got cancer it may be a bit late but dietary and
lifestyle changes can certainly slow it down and even cure if it is
not the fast spreading type and you don't store much PUFAs such as the
linoleic acid in your adipose tissues. Inflammation and its mediators
derived from arachidonic acid (AA) are the main culprits in
carcinogenesis so the easiest and most natural way to prevent cancer
is to avoid the fatty acids which are used by the body to manufacture
AA instead of trying to block its action by different antioxidants and
expensive supplements and fish oil which have other negative effects.
The following citation backs up my note about the main role of AA
metabolites in carcinogenesis (note all the talk about LOX and COX
directly concerns AA):
QUOTE:
Inflammatory mediator-related pathways
Tumor necrosis factor-a (TNF-a), is a pro-inflammatory
cytokine with a wide variety of biological functions in
inflammation like tissue remodeling, alteration of epithelial
barrier permeability, increasing vascular permeability,
activation of macrophages, recruitment of inflammatory cells,
and upregulation of cell adhesion molecules[67]. TNF-a can
be produced and released by activated monocytes, macrophages,
T cells, and mast cells. The induction of pro-inflammatory
genes by TNF has been linked to most diseases.
Almost all cell types, when exposed to TNF, activate NF-kB,
leading to the expression of inflammatory genes. These
include pro-inflammatory cytokines, chemokines, COX-2,
inducible nitric oxide synthase (iNOS), lipoxygenase-2 (LOX-
2), and cell adhesion molecules. TNF has been found to be
a growth factor for most tumor cells[68]. These include ovarian
cancer cells, cutaneous T cell lymphoma[69], acute myelogenous
leukemia[70], and B cell lymphoma[71]. Because of
the critical role of TNF in mediating tumorigenesis, agents
that can suppress TNF activity have potential for the therapy
of TNF-linked diseases. Moore et al reported that TNF-a
knockout mice have been shown to be resistant to skin carcinogenesis[
72], suggesting that neutralization of TNF-a production
may be useful in cancer treatment and prevention.
Phytochemicals such as curcumin[73], green tea polyphenols
EGCG[74] and resveratrol[75] have been shown to suppress
TNF production.
Arachidonic acid (AA) metabolism diverges into the COX
and the LOX pathways (Figure 3). The COX pathway leads
to prostaglandin (PG) and thromboxane production and the
LOX pathway leads to the leukotrienes (LTs) and
hydroperoxyeicosatetraenoic
acids (HPETEs). These classes of
inflammatory molecules exert profound biological effects that
enhance the development and progression of human cancers.
COX-1 and 2 are the rate-limiting enzymes in the conversion
of AA to PGs (Figure 3). The two COX isoforms of PGH
synthase have distinct tissue distributions and physiological
functions. COX-1 is constitutively expressed in many
tissues and cell types, whereas the inducible isoenzyme
COX-2 is pro-inflammatory in nature and expressed only in
response to certain stimuli such as mitogens, cytokines,
growth factors, or hormones. COX-2 is overexpressed in
practically every pre-malignant and malignant condition
involving the colon, liver, pancreas, breast, lung, bladder,
skin, stomach, head and neck[76]. Depending on the stimulus
and the cell type, several transcription factors including
AP-1, NF-IL-6, and NF-kB can stimulate COX-2 transcription[
76]. AA can also be converted to leukotrienes (LTs) by
the action of 5-LOX (Figure 3). The first step in the 5-LOX
cascade consists of activation of the enzyme by 5-LOXactivating
protein, which leads to the formation of the LTs
and HPETEs. These LTs induce the synthesis and release of
other pro-inflammatory mediators such as IL-8 and plateletactivating
factor. Several dietary components including
curcumin[77], genistein[78], green tea catechins[79], and resveratrol[
80] have been shown to suppress COX-2 and LOXs.
Plummer et al. have conducted a dose-escalation pilot study
of a standardized formulation of curcuma extract in 15 patients
with advanced colorectal cancer, analysis of basal and
LPS-induced PGE2 production during treatment demonstrated
a trend toward dose-dependent inhibition[81]. Also,
Garcea et al have reported that administration of curcumin
(3 600 mg) significantly decreased M1G levels in human
malignant colorectal tissue but COX-2 protein levels in
malignant colorectal tissue were not affected by curcumin[82].
Nitric oxide synthase (NOS) is mainly localized in astrocytes
and microglia, and catalyzes the oxidative deamination of Larginine
to produce nitric oxide (NO), a potent pro-inflammatory
mediator. Excess production of iNOS-mediated NO is
involved in inflammatory and immunological disorders, pain,
neurological diseases, atherosclerosis, and cancer. Several
phytochemicals and dietary agents have been investigated
for their effects on NOS. Recently, Lee et al have reported
that 7-carboxymethyloxy-3',4',5’-trimethoxyflavone have
inhibitory effects on Helicobacter pylori-induced iNOS
expression and NF-kB activation in AGS human gastric cancer
cells[83]. Also, Kim et al found that Japanese plants
strongly inhibited LPS- and IFN-g-stimulated NO generation
in RAW 264.7 murine macrophages[84].
UNQUOTE.
SOURCE: Acta Pharmacologica Sinica
Volume 28 Issue 9 Page 1409-1421, September 2007
doi:10.1111/j.1745-7254.2007.00694.x
http://www.blackwell-synergy.com/doi/abs/10.1111/j.1745-7254.2007.00694.x
Taka
.
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