fruit, vegetables and herbs is good for our health. Many members of the
public, a majority of the medical and healing professions, many scientists
and several Governments all accept this, and medical advice is to eat at
least five portions of fruit or vegetables each day. The medical and scientific
evidence shows that a diet rich in fruit and vegetables helps to combat
cancer, amongst other diseases. But how do fruit, vegetables and herbs ward
off cancer? And how can we maximise this protection? There is probably more
than just one single mechanism whereby plants are able to act against human
cancer, and there are several scientifically researched and published theories,
but no definitive answers.
is also the case that conventional chemotherapy against cancer, using synthetic
drugs, is beset by widespread and severely debilitating side effects. A
team of research scientists and natural products specialists in Leicester
believe that a group of natural plant compounds called Salvestrols may provide
part of the answer. They believe that Salvestrols can, on the one hand,
help to explain how plants prevent cancer, and on the other hand offer a
treatment for cancer with far fewer side effects.
Salvestrol Concept explains how the body defends and heals itself from cancer,
using natural plant compounds in the diet and a special enzyme in cancer
cells. It is based on the combined research of Professor Gerry Potter (a
medicinal chemist) and Professor Dan Burke (a pharmacologist), together
with Nature’s Defence (UK) Ltd (a manufacturer of natural products).
Salvestrols are a new class of natural anticancer chemicals, which are found
in plants and safely eaten in the diet. Initially non-toxic to the body’s
normal cells, Salvestrols become activated inside human cancer cells by
a special enzyme, CYP1B1 (pronounced “sip one bee one”). The
activated Salvestrols then cause the cancer cells to stop growing or die,
without harming normal cells. This specificity of action is possible because
CYP1B1 is an intrinsic component of cancer cells and occurs in all of the
wide range of different types of cancer that have been studied to date,
but is to all intents and purposes absent from normal cells.
AGRICULTURE MINIMIZES SALVESTROLS
are not a single chemical type of plant compound, but are defined on the
basis of their mechanism of anticancer action as summarized above. Moreover,
it is now clear that several food plants and plant-rich diets that have
traditionally been considered to offer protection against cancer can be
good sources of Salvestrols. Salvestrols can be particularly high in many
red or green health-giving plant species, including fruit, berries, vegetables
and herbs. Good natural sources of Salvestrols include strawberries, cranberries,
oranges, tangerines and grapes. Olives are also a good source of Salvestrols.
Several herbs contain appreciable levels of Salvestrols, including basil,
parsley, sage, rosemary, thyme, mint, artichoke, scutellaria and the roots
of milk thistle and dandelion. Unfortunately modern agricultural practices
have succeeded in minimizing the levels of Salvestrols in fruits and vegetables,
through a combination of the development of modern plant varieties, the
use of agrochemical crop sprays and the selective processing of harvested
fruit. Recent research into the sources of Salvestrols has revealed that
levels of these compounds are up to 30-fold higher in organic produce.
reason why fruits produce Salvestrols is that many of these compounds are
natural anti-pathogenic agents, which the plants produce in response to
attack by pathogens. However, when fruit crops are routinely sprayed with
synthetic agrochemicals they rarely get attacked by the pathogens and so
lack the main stimulus to produce Salvestrols.
Salvestrols are bitter tasting and for this reason they are sometimes deliberately
removed by manufacturers from fruit juice. Salvestrols generally do not
dissolve readily in water and so are found more in the skins, pulp and stones
of fruit rather than in the pure juice. Consequently, when fruit juices
are clarified much of their Salvestrol content is removed.
traditional wine-making techniques, which ban the use of agrochemicals on
the vines and ferment the grapes in contact with their skins, tend to give
higher levels of Salvestrols in the ensuing wine compared to modern winemaking
techniques, in which the pulp of grapes from agrochemical-treated vines
is separated from the skins before fermentation. This is because (i) the
absence of pathogens encourages the grapes to produce Salvestrols and (ii)
the alcohol that is formed during the fermentation process dissolves the
Salvestrols out of the grape skins (Salvestrols being poorly soluble in
water). For different reasons, traditionally milled cloudy olive oil often
has higher levels of Salvestrols than clear oil produced using modern methods.
varieties of several fruits have higher Salvestrol contents than newer varieties.
This is probably because the newer varieties have been selected for their
sweeter taste (Salvestrols are bitter-tasting) and any greater susceptibility
to pathogens (due to their lower Salvestrol levels) is overcome by modern
agrochemical-dependent methods of agriculture.
Salvestrol Concept is firmly based on extensive scientific research, spanning
a period of more than ten years. In the early 1990’s Professor Burke’s
research group found that a certain enzyme protein, called CYP1B1, was clearly
present in the tumour cells of a wide variety of human cancers, but was
undetectable in the normal cells of the corresponding healthy tissues.1
The technical description for this is that CYP1B1 is highly overexpressed
in cancer cells. This has since been confirmed by a number of eminent laboratories
across the world, including the USA and Japan.2,3 Then around the year 2000
Professor Potter, working with Professor Burke, discovered that, through
a process called metabolism, CYP1B1 brings about a subtle change in the
chemical structures of certain plant compounds and turns them into slightly
different chemicals, called metabolites, that are potent anticancer toxins.4
This is the process of activation, and the anticancer effects are due, not
directly to the plant chemicals themselves, but to their metabolites which
are generated in the human cancer cells. Finally, in an inspirational moment,
Professor Potter realised that this could help explain how many different
types of plants combat cancer and how many plant compounds that were previously
thought to be without direct anticancer activity could, indeed, be able
to attack cancer cells. He coined the term “Salvestrols” to
describe plant chemicals that are activated against cancer in this way.
to summarize, there are three components to the Salvestrol concept:
- the natural, plant-based chemicals;
- the special enzyme that is uniquely intrinsic to cancer cells;
metabolites – the activated anticancer toxins.
are taken in the diet. When Salvestrols encounter human cancer cells they
are absorbed into the cells, where CYP1B1 activates them by converting them
into slightly different chemicals, i.e. the Salvestrol metabolites, which
then act to poison the cancer cell. In contrast, normal cells generally
lack CYP1B1, and so although Salvestrols are absorbed into normal cells
they are not converted into active metabolites, the normal cells are not
poisoned and the Salvestrols are excreted from normal cells in unaltered
natural chemicals and synthetic medicinal drugs other than Salvestrols can
become activated in healthy tissues of the body (although not by CYP1B1).
However, the key feature of Salvestrols is that they are activated only
inside the cancer cells which they then arrest or kill, and not in healthy
cells. And although there are hundreds of different enzymes which are ubiquitous
in the body, CYP1B1 is virtually confined to cancer cells.
are currently identified by testing plant compounds against CYP1B1-containing
human cancer cells and non-CYP1B1-containing human cells, in culture in
the laboratory. By definition, Salvestrols kill CYP1B1-containing cells
in preference to cells that lack CYP1B1. The first Salvestrol to be identified
was resveratrol, a chemical from grapes that is notably present in red wine
and which is widely credited with cancer preventative properties. Resveratrol
is metabolised by CYP1B1 into a metabolite, piceatannol, which is a known
anticancer toxin.4 Other, more powerful Salvestrols have since been
identified in a wide variety of fruits, including tangerines, strawberries
and cranberries. The results for a typical Salvestrol, codenamed Q40, are
shown in Figure 2. Human cells in culture were treated with a range of Q40
concentrations and then the number of cells surviving at each concentration
was measured under a microscope. By definition, 100% of the cells survived
when no Q40 was added. The results show that breast cancer cells which contain
CYP1B1 (MDA-MB-468 cells) were killed at a very low concentration of Q40,
and at a much lower Q40 concentration than non-cancer cells that lack CYP1B1
(MCF10 cells). (All chemicals kill any cells if used at a high enough concentration,
but the concentration needed to kill CYP1B1-lacking cells could never be
achieved in practice in living people). These results show that Salvestrol
Q40 is a highly selective killer of CYP1B1-containing cells. The search
for powerful Salvestrols looks for compounds with the twin attributes of
(i) killing CYP1B1-containing cancer cells at a very low concentration and
(ii) showing a very large difference between the concentration able to kill
CYP1B1-containing cells and a higher concentration needed to kill CYP1B1-lacking
Salvestrol Concept deems CYP1B1 to be a tumour suppressor and rescue mechanism,
which has evolved to enable the body to defend and heal itself against cancer
by activating some of the natural compounds found in edible fruits and other
dietary plants. CYP1B1 is present in the cells of all the different types
of cancer that have been investigated to date, including all the most prevalent
cancers, for example bladder, brain, breast, colon, oesophagus, kidney,
liver, lung, lymph node, ovary, skin, stomach, testis and uterus. CYP1B1
can be thought of as a Trojan Horse inside the cancer cells, which merely
has to be provided with Salvestrols in the diet in order to unleash a stream
of chemical agents that are deadly to the cancer cells. In other words,
in CYP1B1 the body seems to have provided cancer cells with the seeds of
their own destruction.
scientists generally believe that single cancer cells are continually forming
in the human body and that most of these are destroyed by the body before
they develop into malignant tumours. Salvestrols in the diet are a mechanism
by which this ongoing prevention of cancer can occur.
terms of cancer treatment, most current anticancer chemotherapy is beset
by serious side effects. These occur because most anticancer drugs are cell
poisons that do not distinguish between cancer cells and many types of healthy
cells. Because Salvestrols are activated into anticancer toxins only within
cancer cells, they offer the possibility of anticancer treatment without
the awful side effects.
because of modern varieties and the use of synthetic agrochemicals and post-harvest
manufacturing techniques, simply eating fresh or processed fruit probably
provides us with much less Salvestrols than we expect.
expression of cytochrome P450 CYP1B1. Murray, G.I. et al., Cancer Research,
vol. 57, 3026-3031 (1997).
2 Unexpected association between induction of immunity to the universal
tumor antigen CYP1B1 and response to next therapy. Gribben, J.G. et al.,
Clinical Cancer Research, vol. 11, 4430-4436 (2005).
3 Cytochrome P450 CYP1B1 is overexpressed and regulated by hypomethylation
in prostate cancer. Tokizane, T. et al., Clinical cancer Research, vol.
11, 5793-5801 (2005).
4 The cancer preventative agent resveratrol is converted to the anticancer
agent piceatannol by the cytochr ome P450 enzyme CYP1B1. Potter, G.A. et
al., British Journal of Cancer, vol. 86, 774-778 (2002).