Diet and cancer
Encyclopedia
Diet and cancer are associated. While it is not yet possible to provide quantitative estimates of the overall risks, it has been estimated that 35 percent of cancer
deaths may be related to dietary factors. Almost all cancers (80–90%) are caused by environmental factors, and of these, 30–40% of cancers are directly linked to the diet. Studies conducted over the years have show a strong correlation between diet and cancer. A comprehensive worldwide report Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective
compiled by World Cancer Research Fund
and American Institute for Cancer Research
reports that there is significant relation between lifestyle (including food consumption) and cancer prevention. The same report recommends eating mostly foods of plant origin and aiming to meet nutritional needs through diet alone, while limiting consumption of cholesterol-dense foods, red meat, alcoholic drinks and salt, and avoiding sugary drinks and processed meat.
In addition to antioxidants, vitamins and trace minerals have a powerful effect on free radicals in terms of neutralizing them, as previously described, and preventing damage to the body's cells.
Berries have been causing a lot of commotion and promise in the world of cancer research. The darker the berry, the better in terms of being more packed with nutrients that is better at warding off cancer. Research has been putting the spot light on black raspberries and their ability to reduce oxidative stress and gastroesophageal reflux disease, each of which causes damage to the esophageal cells. Close runner-ups to the black raspberry are blueberries, blackberries, strawberries, and cranberries. These berries are high in vitamin C
, fiber, and ellagic acid
, which can prevent skin cancer. In addition to these nutrients, the American Association for Cancer Research found that berries are extremely high in polyphenol phytochemicals, and some research is suggesting that these phytochemicals are what is inhibiting tumor growth, more so than vitamins and minerals. These phytochemicals have the ability to interfere with tumor development, probably due to their natural job of protecting plants and their structures, as well as maintaining their vibrant colors (2007). Beta-carotene and lycopene are two prevalent nutrients that have shown a lot of promise in their capabilities to slow tumor growth.
, especially cancer
of the colon.
A few studies have also shown a reduced risk for cancers of the breast, rectum
, oral cavity, pharynx
, stomach, and other sites with diets rich in fruits, vegetables and grain products. Numerous studies have found evidence that carotenoid
s reduce the risk of some cancers. The evidence is particularly strong for lung cancer
, even after taking smoking into account. Vitamin C
is found in fruits, particularly citrus fruits and juices, and in green vegetables, as well as in some fortified foods. Of a group of epidemiologic studies investigating the role of vitamin C
, three-quarters found that vitamin C
, or fruit rich in vitamin C
, provides significant protection.
A leaner diet is believed to lower cancer risk. Tomato
es, calcium
, agaricus blazei
mushrooms http://www3.interscience.wiley.com/cgi-bin/fulltext/121398729/PDFSTART?CRETRY=1&SRETRY=0, other minerals, saponin
s, sausage tree, sea mat, cat's claw
, and licorice are believed to prevent or suppress different kinds of cancerous tumors. Currently there is not enough evidence for using mushrooms or mushroom extracts in the treatment of cancer, but there is significant potential for research in the area and future clinical trials, due to the numerous scientific studies which have shown they may offer a beneficial effect.
, http://www3.interscience.wiley.com/cgi-bin/fulltext/121398729/PDFSTART?CRETRY=1&SRETRY=0, Maitake, and Trametes versicolor
. Research suggests the compounds in medicinal mushrooms most responsible for up-regulating the immune system and providing an anti-cancer effect, are a diverse collection of polysaccharide
compounds, particularly beta-glucans. Beta-glucans are known as "biological response modifiers", and their ability to activate the immune system is well documented. Specifically, beta-glucans stimulate the innate
branch of the immune system. Research has shown beta-glucans have the ability to stimulate macrophage
, NK cells, T cells, and immune system cytokines. The mechanisms in which beta-glucans stimulate the immune system is only partially understood. One mechanism in which beta-glucans are able to activate the immune system, is by interacting with the Macrophage-1 antigen (CD18
) receptor on immune cells.
A highly purified compound isolated from the medicinal mushroom Trametes versicolor
, known as Polysaccharide-K
, has become incorporated into the health care system of a few countries, such as Japan
. Japan's Ministry of Health, Labour and Welfare
approved the use of Polysaccharide-K
in the 1980s, to stimulate the immune systems of patients undergoing chemotherapy.
The belief that dietary fiber prevents these cancers was based on epidemiological evidence showing a very low incidence in the developing world. Dr. Denis Burkitt was the main proponent of this theory, and his 1979 best-selling book, "Don't Forget Fibre in Your Diet," was translated into nine languages. Less well-known is his theory, mentioned in the book, that the squatting defecation posture used in the developing world where Ottoman toilets are more widespread than the Western world is also a preventative factor, especially for colon diseases.
Although numerous cellular mechanisms are involved in food intake, many investigations over the past decades have pointed out defects in the methionine
metabolic pathway as cause of carcinogenesis. For instance, deficiencies of the main dietary sources of methyl donors, methionine
and choline
, lead to the formation of liver cancer
in rodents. Methionine
is an essential amino acid
that must be provided by dietary intake of proteins or methyl donors (choline
and betaine found in beef, eggs and some vegetables). Assimilated methionine is transformed in S-adenosyl methionine
(SAM) which is a key metabolite
for polyamine
synthesis, e.g. spermidine
, and cysteine
formation (see the figure on the right). Methionine
breakdown products are also recycled back into methionine
by homocysteine
remethylation and methylthioadenosine (MTA) conversion (see the figure on the right). Vitamins B6, B12, folic acid
and choline
are essential cofactors for these reactions. SAM is the substrate for methylation
reactions catalyzed by DNA, RNA and protein methyltransferase
s.
The products of these reactions are methylated DNA
, RNA
or proteins and S-adenosylhomocysteine (SAH). SAH has a negative feedback on its own production as an inhibitor of methyltransferase enzymes. Therefore SAM:SAH ratio directly regulates cellular methylation, whereas levels of vitamins B6, B12, folic acid and choline
regulates indirectly the methylation
state via the methionine
metabolism cycle. A near ubiquitous feature of cancer
is a maladaption of the methionine
metabolic pathway
in response to genetic or environmental conditions resulting in depletion of SAM and/or SAM-dependent methylation
. Whether it is deficiency in enzymes such as methylthioadenosine phosphorylase, methionine
-dependency of cancer
cells, high levels of polyamine
synthesis in cancer
, or induction of cancer through a diet deprived of extrinsic methyl donors or enhanced in methylation
inhibitors, tumor
formation is strongly correlated with a decrease in levels of SAM in mice, rats and humans. Many indirect and thinly circumstantial theories have been put forth related to methylation
status of DNA or attacks upon the capacity for DNA mutation and repair. The discovery that methyltransferases whose activity would be directly influenced by SAM levels also act as tumor suppressors potentially provides a more direct bridge. This has important ramifications for chemoprevention strategies as well as chemotherapy
.
N-methyltransferase
-4 (PRMT4) methylation
of arginine
residues within proteins plays a critical key role in transcriptional regulation (see the PRMT4 pathway on the left). PRMT4 binds to the classes of transcriptional activators known as p160 and CBP/p300. The modified forms of these proteins are involved in stimulation of gene expression
via steroid hormone receptor
s. Significantly, PRMT4 methylates core histone
s H3 and H4, which are also targets of the histone
acetylase activity of CBP/p300 coactivators. PRMT4 recruitment chromatin
by binding to coactivators increases histone
methylation
and enhances the accessibility of promoter regions for transcription
. Methylation
of the transcriptional coactivator CBP by PRMT4 inhibits binding to CREB and thereby partitions the limited cellular pool of CBP for steroid hormone
receptor interaction.
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
deaths may be related to dietary factors. Almost all cancers (80–90%) are caused by environmental factors, and of these, 30–40% of cancers are directly linked to the diet. Studies conducted over the years have show a strong correlation between diet and cancer. A comprehensive worldwide report Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective
Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective
Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective, also known as the Expert Report, was an expert report published by the World Cancer Research Fund global network in 2007....
compiled by World Cancer Research Fund
World Cancer Research Fund
World Cancer Research Fund International is a not-for-profit association, established by royal decree in Belgium, with headquarters in London, UK...
and American Institute for Cancer Research
American Institute for Cancer Research
The American Institute for Cancer Research is a large American cancer research organization associated with the World Cancer Research Fund umbrella organization.Its stated mission is:...
reports that there is significant relation between lifestyle (including food consumption) and cancer prevention. The same report recommends eating mostly foods of plant origin and aiming to meet nutritional needs through diet alone, while limiting consumption of cholesterol-dense foods, red meat, alcoholic drinks and salt, and avoiding sugary drinks and processed meat.
Nutrients in food
Nutrients in our food can fight cancer by protecting our bodies' cells from mutations caused mainly by carcinogens and free radicals. Antioxidants have been shown to minimize the damaging effects of free radicals and fight off tumors. Free radicals cause oxidative damage to DNA and mutate cells, which then proliferate into a tumor and thus cause cancer. The oxidative damage can be prevented when nutrients bind the free oxygen, therefore prohibiting it from roaming the body and damaging cells.In addition to antioxidants, vitamins and trace minerals have a powerful effect on free radicals in terms of neutralizing them, as previously described, and preventing damage to the body's cells.
Importance of the whole food
Although many foods with certain nutrients have been demonstrated to be as effective in fighting off cancer, isolated consumption of these elements does not seem to confer the same benefits. Several studies have found that when isolating the nutrients by extracting it from the food source it is naturally found in, no benefits regarding cancer prevention were found. However, when increased amounts of the whole food were used, cancers were limited.Fruits and vegetables
Fresh or frozen fruits and vegetables are both good, and contrary to common thought, frozen produce is just as nutrient dense as fresh produce, while dried produce is often sweetened, causing some of the nutrients to be broken down. Studies have shown produce consumption is effective in reducing cancers, especially in the gastrointestinal tract, lowering cancer rates by 22% and mortality to dietary related cancer by 11%.Berries have been causing a lot of commotion and promise in the world of cancer research. The darker the berry, the better in terms of being more packed with nutrients that is better at warding off cancer. Research has been putting the spot light on black raspberries and their ability to reduce oxidative stress and gastroesophageal reflux disease, each of which causes damage to the esophageal cells. Close runner-ups to the black raspberry are blueberries, blackberries, strawberries, and cranberries. These berries are high in vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
, fiber, and ellagic acid
Ellagic acid
Ellagic acid is a natural phenol antioxidant found in numerous fruits and vegetables including blackberries, raspberries, strawberries, cranberries, walnuts, pecans, pomegranates, wolfberry and other plant foods...
, which can prevent skin cancer. In addition to these nutrients, the American Association for Cancer Research found that berries are extremely high in polyphenol phytochemicals, and some research is suggesting that these phytochemicals are what is inhibiting tumor growth, more so than vitamins and minerals. These phytochemicals have the ability to interfere with tumor development, probably due to their natural job of protecting plants and their structures, as well as maintaining their vibrant colors (2007). Beta-carotene and lycopene are two prevalent nutrients that have shown a lot of promise in their capabilities to slow tumor growth.
Flavonoids
Flavonoids and catechins are nutrients that give foods a bitter taste, but they also are emerging as great anticancer agents. After looking into these nutrients further, Abdulla et al. found the best sources to be green and black teas, chocolate, wine, and grapes (2000). He also found that catechins are a powerful form of antioxidant that act as a powerful inhibitor of cancer growth. In fact, catechins are 100 times more powerful than vitamin C and 25 times more powerful than vitamin E in their antioxidant/growth inhibitor powers. The flavonoids and catechins together have proven the ability to protect cells from x-ray damage, block the progression of the cell cycle, and inhibit mutations (2000). Other foods high in flavonoids are garlic, onions, shallots, and leeks, which also contain vitamin C, selenium, and sulfur compounds that together, increase the metabolic disposal of chemical carcinogens, thus lowering the risk of cells turning cancerous.Probiotics
Probiotics are bacteria that live in our gastrointestional tract and aid us in digestion as well as provide other benefits for its host. Ruize suggests that one of these benefits is their ability to eliminate procarcinogenic substances before they can turn carcinogenic. The probiotics are capable of altering certain enzymes (such as b-glucuronidase and nitro-reductase) that turn procarcinogens into carcinogenic agents by neutralizing the bad bacteria enzymes. Essentially, the good bacteria is cleansing the GI tract of harmful substances, such as poisonous bacteria and extraneous pollutants, found in the environment and our food chain. Without the probiotics, the immune system would be left to clean the body alone, causing a work overload and probably not as thorough, thus the probiotics are good because they help the immune system to keep toxins out of our intestines.Reducing-risk factors
Increasing evidence suggests that diets high in foods containing fibre (or fiber) are associated with a reduced risk for cancerCancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
, especially cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
of the colon.
A few studies have also shown a reduced risk for cancers of the breast, rectum
Rectum
The rectum is the final straight portion of the large intestine in some mammals, and the gut in others, terminating in the anus. The human rectum is about 12 cm long...
, oral cavity, pharynx
Pharynx
The human pharynx is the part of the throat situated immediately posterior to the mouth and nasal cavity, and anterior to the esophagus and larynx. The human pharynx is conventionally divided into three sections: the nasopharynx , the oropharynx , and the laryngopharynx...
, stomach, and other sites with diets rich in fruits, vegetables and grain products. Numerous studies have found evidence that carotenoid
Carotenoid
Carotenoids are tetraterpenoid organic pigments that are naturally occurring in the chloroplasts and chromoplasts of plants and some other photosynthetic organisms like algae, some bacteria, and some types of fungus. Carotenoids can be synthesized fats and other basic organic metabolic building...
s reduce the risk of some cancers. The evidence is particularly strong for lung cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
, even after taking smoking into account. Vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
is found in fruits, particularly citrus fruits and juices, and in green vegetables, as well as in some fortified foods. Of a group of epidemiologic studies investigating the role of vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
, three-quarters found that vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
, or fruit rich in vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
, provides significant protection.
A leaner diet is believed to lower cancer risk. Tomato
Tomato
The word "tomato" may refer to the plant or the edible, typically red, fruit which it bears. Originating in South America, the tomato was spread around the world following the Spanish colonization of the Americas, and its many varieties are now widely grown, often in greenhouses in cooler...
es, calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
, agaricus blazei
Agaricus blazei
Agaricus subrufescens is a species of mushroom, commonly known as almond mushroom, mushroom of the sun, God's mushroom, mushroom of life, royal sun agaricus, jisongrong or himematsutake and by a number of other...
mushrooms http://www3.interscience.wiley.com/cgi-bin/fulltext/121398729/PDFSTART?CRETRY=1&SRETRY=0, other minerals, saponin
Saponin
Saponins are a class of chemical compounds, one of many secondary metabolites found in natural sources, with saponins found in particular abundance in various plant species...
s, sausage tree, sea mat, cat's claw
Cat's claw
Cat's claw or Cat's Claws is a common name for several plants:* Acacia greggii, a tree species native to the southwestern United States and northern Mexico...
, and licorice are believed to prevent or suppress different kinds of cancerous tumors. Currently there is not enough evidence for using mushrooms or mushroom extracts in the treatment of cancer, but there is significant potential for research in the area and future clinical trials, due to the numerous scientific studies which have shown they may offer a beneficial effect.
Mushrooms
Some mushrooms offer an anti-cancer effect, which is thought to be linked to their ability to up-regulate the immune system. Some mushrooms known for this effect include, Reishi, Agaricus blazeiAgaricus blazei
Agaricus subrufescens is a species of mushroom, commonly known as almond mushroom, mushroom of the sun, God's mushroom, mushroom of life, royal sun agaricus, jisongrong or himematsutake and by a number of other...
, http://www3.interscience.wiley.com/cgi-bin/fulltext/121398729/PDFSTART?CRETRY=1&SRETRY=0, Maitake, and Trametes versicolor
Trametes versicolor
Trametes versicolor — formerly known as Coriolus versicolor and Polyporus versicolor — is an extremely common polypore mushroom which can be found throughout the world. Versicolor means 'of several colours' and it is true that this mushroom is found in a wide variety of different colours. T...
. Research suggests the compounds in medicinal mushrooms most responsible for up-regulating the immune system and providing an anti-cancer effect, are a diverse collection of polysaccharide
Polysaccharide
Polysaccharides are long carbohydrate molecules, of repeated monomer units joined together by glycosidic bonds. They range in structure from linear to highly branched. Polysaccharides are often quite heterogeneous, containing slight modifications of the repeating unit. Depending on the structure,...
compounds, particularly beta-glucans. Beta-glucans are known as "biological response modifiers", and their ability to activate the immune system is well documented. Specifically, beta-glucans stimulate the innate
Innate immune system
The innate immune system, also known as non-specific immune system and secondary line of defence, comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner...
branch of the immune system. Research has shown beta-glucans have the ability to stimulate macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
, NK cells, T cells, and immune system cytokines. The mechanisms in which beta-glucans stimulate the immune system is only partially understood. One mechanism in which beta-glucans are able to activate the immune system, is by interacting with the Macrophage-1 antigen (CD18
CD18
Integrin beta-2 is a protein that in humans is encoded by the ITGB2 gene.It is the beta subunit of four different structures:* LFA-1 * Macrophage-1 antigen * Integrin alphaXbeta2...
) receptor on immune cells.
A highly purified compound isolated from the medicinal mushroom Trametes versicolor
Trametes versicolor
Trametes versicolor — formerly known as Coriolus versicolor and Polyporus versicolor — is an extremely common polypore mushroom which can be found throughout the world. Versicolor means 'of several colours' and it is true that this mushroom is found in a wide variety of different colours. T...
, known as Polysaccharide-K
Polysaccharide-K
Polysaccharide-K is a protein-bound polysaccharide, which is used as an immune system boosting agent in the treatment of cancer in some countries in Europe as well as China and Japan. In Japan, PSK is approved as an adjuvant for cancer therapy and is covered by government health insurance...
, has become incorporated into the health care system of a few countries, such as Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
. Japan's Ministry of Health, Labour and Welfare
Ministry of Health, Labour and Welfare (Japan)
The ' is a cabinet level ministry of the Japanese government. It is commonly known as Kōrō-shō in Japan. This ministry provides regulations on maximum residue limits for agricultural chemicals in foods, basic food and drug regulations, standards for foods, food additives, etc.It was formed with...
approved the use of Polysaccharide-K
Polysaccharide-K
Polysaccharide-K is a protein-bound polysaccharide, which is used as an immune system boosting agent in the treatment of cancer in some countries in Europe as well as China and Japan. In Japan, PSK is approved as an adjuvant for cancer therapy and is covered by government health insurance...
in the 1980s, to stimulate the immune systems of patients undergoing chemotherapy.
Alcohol
Alcohol is a risk factor for cancers of the mouth, esophagus, pharynx, and larynx, breast cancer, colorectal cancer, and liver cancer.Contrary evidence
More recent studies have cast doubt on the claim that dietary fiber reduces the risk of colon cancer. Regarding prostate cancer, a major 2002 study concluded that "A low-fat, high-fiber diet heavy in fruits and vegetables has no impact on PSA levels in men over a four-year period, and does not affect the incidence of prostate cancer."The belief that dietary fiber prevents these cancers was based on epidemiological evidence showing a very low incidence in the developing world. Dr. Denis Burkitt was the main proponent of this theory, and his 1979 best-selling book, "Don't Forget Fibre in Your Diet," was translated into nine languages. Less well-known is his theory, mentioned in the book, that the squatting defecation posture used in the developing world where Ottoman toilets are more widespread than the Western world is also a preventative factor, especially for colon diseases.
Methionine metabolism
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
metabolic pathway as cause of carcinogenesis. For instance, deficiencies of the main dietary sources of methyl donors, methionine
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
and choline
Choline
Choline is a water-soluble essential nutrient. It is usually grouped within the B-complex vitamins. Choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation....
, lead to the formation of liver cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
in rodents. Methionine
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
is an essential amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
that must be provided by dietary intake of proteins or methyl donors (choline
Choline
Choline is a water-soluble essential nutrient. It is usually grouped within the B-complex vitamins. Choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation....
and betaine found in beef, eggs and some vegetables). Assimilated methionine is transformed in S-adenosyl methionine
S-Adenosyl methionine
S-Adenosyl methionine is a common cosubstrate involved in methyl group transfers. SAM was first discovered in Italy by G. L. Cantoni in 1952. It is made from adenosine triphosphate and methionine by methionine adenosyltransferase . Transmethylation, transsulfuration, and aminopropylation are the...
(SAM) which is a key metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
for polyamine
Polyamine
A polyamine is an organic compound having two or more primary amino groups .This class of compounds includes several synthetic substances that are important feedstocks for the chemical industry, such as ethylene diamine , 1,3-diaminopropane , and hexamethylenediamine...
synthesis, e.g. spermidine
Spermidine
Spermidine is a polyamine involved in cellular metabolism. Its known actions include:#Inhibition of neuronal nitric oxide synthase, nNOS#Assisting the in vitro process of transcribing RNA via stimulation of T4 polynucleotide kinase and T7 RNA polymerase activity; it binds to and precipitates DNA...
, and cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
formation (see the figure on the right). Methionine
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
breakdown products are also recycled back into methionine
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
by homocysteine
Homocysteine
Homocysteine is a non-protein amino acid with the formula HSCH2CH2CHCO2H. It is a homologue of the amino acid cysteine, differing by an additional methylene group. It is biosynthesized from methionine by the removal of its terminal Cε methyl group...
remethylation and methylthioadenosine (MTA) conversion (see the figure on the right). Vitamins B6, B12, folic acid
Folic acid
Folic acid and folate , as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9...
and choline
Choline
Choline is a water-soluble essential nutrient. It is usually grouped within the B-complex vitamins. Choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation....
are essential cofactors for these reactions. SAM is the substrate for methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
reactions catalyzed by DNA, RNA and protein methyltransferase
Methyltransferase
A methyltransferase is a type of transferase enzyme that transfers a methyl group from a donor to an acceptor.Methylation often occurs on nucleic bases in DNA or amino acids in protein structures...
s.
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
, RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
or proteins and S-adenosylhomocysteine (SAH). SAH has a negative feedback on its own production as an inhibitor of methyltransferase enzymes. Therefore SAM:SAH ratio directly regulates cellular methylation, whereas levels of vitamins B6, B12, folic acid and choline
Choline
Choline is a water-soluble essential nutrient. It is usually grouped within the B-complex vitamins. Choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation....
regulates indirectly the methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
state via the methionine
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
metabolism cycle. A near ubiquitous feature of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
is a maladaption of the methionine
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
metabolic pathway
Metabolic pathway
In biochemistry, metabolic pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by a series of chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function...
in response to genetic or environmental conditions resulting in depletion of SAM and/or SAM-dependent methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
. Whether it is deficiency in enzymes such as methylthioadenosine phosphorylase, methionine
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
-dependency of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
cells, high levels of polyamine
Polyamine
A polyamine is an organic compound having two or more primary amino groups .This class of compounds includes several synthetic substances that are important feedstocks for the chemical industry, such as ethylene diamine , 1,3-diaminopropane , and hexamethylenediamine...
synthesis in cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
, or induction of cancer through a diet deprived of extrinsic methyl donors or enhanced in methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
inhibitors, tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
formation is strongly correlated with a decrease in levels of SAM in mice, rats and humans. Many indirect and thinly circumstantial theories have been put forth related to methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
status of DNA or attacks upon the capacity for DNA mutation and repair. The discovery that methyltransferases whose activity would be directly influenced by SAM levels also act as tumor suppressors potentially provides a more direct bridge. This has important ramifications for chemoprevention strategies as well as chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
.
Arginine methyltransferase
Protein arginineArginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
N-methyltransferase
Methyltransferase
A methyltransferase is a type of transferase enzyme that transfers a methyl group from a donor to an acceptor.Methylation often occurs on nucleic bases in DNA or amino acids in protein structures...
-4 (PRMT4) methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
of arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
residues within proteins plays a critical key role in transcriptional regulation (see the PRMT4 pathway on the left). PRMT4 binds to the classes of transcriptional activators known as p160 and CBP/p300. The modified forms of these proteins are involved in stimulation of gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
via steroid hormone receptor
Hormone receptor
A hormone receptor is a receptor protein on the surface of a cell or in its interior that binds to a specific hormone. The hormone causes many changes to take place in the cell....
s. Significantly, PRMT4 methylates core histone
Histone
In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...
s H3 and H4, which are also targets of the histone
Histone
In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...
acetylase activity of CBP/p300 coactivators. PRMT4 recruitment chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
by binding to coactivators increases histone
Histone
In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...
methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
and enhances the accessibility of promoter regions for transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
. Methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
of the transcriptional coactivator CBP by PRMT4 inhibits binding to CREB and thereby partitions the limited cellular pool of CBP for steroid hormone
Steroid hormone
A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens...
receptor interaction.
See also
- Alcohol and cancerAlcohol and cancerAlcohol is associated with an increased risk of a number of cancers. 3.6% of all cancer cases and 3.5% of cancer deaths worldwide are attributable to consumption of alcohol. Breast cancer in women is linked with alcohol intake...
- Alcohol and breast cancerAlcohol and breast cancerAlcohol is a risk factor for breast cancer in women.A woman drinking an average of two units of alcohol per day has 8% higher of developing breast cancer than a woman who drinks an average of one unit of alcohol per day...
- DNA methyltransferaseDNA methyltransferaseIn biochemistry, the DNA methyltransferase family of enzymescatalyze the transfer of a methyl group to DNA. DNA methylation serves a wide variety of biological functions...
- Food guide pyramidFood guide pyramidA food guide pyramid is a triangular or pyramid-shaped nutrition guide divided into sections to show the recommended intake for each food group. The first food pyramid was published in Sweden in 1974. The most widely known food pyramid was introduced by the United States Department of Agriculture...
- List of oncology-related terms
- Red meatRed meatRed meat in traditional culinary terminology is meat which is red when raw and not white when cooked. In the nutritional sciences, red meat includes all mammal meat. Red meat includes the meat of most adult mammals and some fowl ....
- Nutritional gatekeeperNutritional gatekeeperNutritional gatekeeper has been used to refer to the person in a household who typically makes the purchasing and preparation decisions related to food. Nutritional gatekeepers can be a parent, grandparent, sibling, or caregiver...