Strategies of Functional Food for Cancer Prevention in Human Beings

Cancer remains a major health problem and one in eight deaths worldwide (vel Szic et al., 2011). The 13.3 million new cases of cancer in 2010 were estimated to cost US$ 290 billion, but the total costs were expected to rise to US$ 458 billion in the year 2030 according to World Economic Forum in 2011. More than half of all cancer cases and deaths worldwide are potentially preventable (Tantamango-Bartley et al., 2013). Numerous studies have demonstrated that natural products play critical roles against cancer (Kuno et al., 2012; Shin et al., 2012; Wu et al., 2013). Cancer biologists have focused on the use of natural products to improve the survival rate of cancer patients. Prevention of chronic diseases is commonly associated with diet, and the consumption of appropriate diets is one of the most effective means for anticancer. Food security is one of this century’s key global challenges (García-Mier et al., 2013). Functional food between food and medicine has globally propagated since 1993 (Swinbanks et al., 1993). The global market of functional foods is estimated at 73 billion euros with an annual 8%–16% growth rate (Szakály et al., 2012). Functional crop are essential for world feeding and its phytochemical enhancement for health, based on their the nutrients and an enormous variety of secondary metabolites, such as phenolic compounds, terpenes, and alkaloids. Bioactive phytochemicals (polyphenols, folic


Introduction
Cancer remains a major health problem and one in eight deaths worldwide (vel Szic et al., 2011).The 13.3 million new cases of cancer in 2010 were estimated to cost US$ 290 billion, but the total costs were expected to rise to US$ 458 billion in the year 2030 according to World Economic Forum in 2011.More than half of all cancer cases and deaths worldwide are potentially preventable (Tantamango-Bartley et al., 2013).Numerous studies have demonstrated that natural products play critical roles against cancer (Kuno et al., 2012;Shin et al., 2012;Wu et al., 2013).Cancer biologists have focused on the use of natural products to improve the survival rate of cancer patients.Prevention of chronic diseases is commonly associated with diet, and the consumption of appropriate diets is one of the most effective means for anticancer.
Food security is one of this century's key global challenges (García-Mier et al., 2013).Functional food between food and medicine has globally propagated since 1993 (Swinbanks et al., 1993).The global market of functional foods is estimated at 73 billion euros with an annual 8%-16% growth rate (Szakály et al., 2012).Functional crop are essential for world feeding and its phytochemical enhancement for health, based on their the nutrients and an enormous variety of secondary metabolites, such as phenolic compounds, terpenes, and alkaloids.Bioactive phytochemicals (polyphenols, folic prostate (7.1%) (Bloom et al., 2011).Almost all cancers (80-90%) are caused by environmental factors (Abdulla et al., 2000), including chemicals (alcohol and smoking), diet (high meats,and salt), obesity, physical inactivity, infection, radiation, physical agents, hormones and other, but heredity cause less than 3-10% of all cancer (http:// en.wikipedia.org/wiki/Cancer).80% of 50 common ingredients from random recipes in a cookbook had articles reporting on their cancer risk (Schoenfeld and Ioannidis, 2013).Aetiology of cancer in Asian populations includes that infectious agents (stomach, liver and cervical cancer),tobacco smoking (lung cancer), excessive alcohol drinking (colorectal and breast cancer), betel nut chewing(oral and esophageal cancer), high caloric and fat intake (breast cancer), salted food intake (stomach cancer), aflatoxin B1(liver cancer), and low fruits and vegetables intake (breast and lung cancer), environmental pollution (lung cancer), and reproductive factors (breast and colorectal cancer) (Park et al., 2008).Major cancer risk factors for dietary substances in human being are as follows: First of all, diet with low whole grains are key factors that cause cancers i.e. the loss of functional components with anticancer from whole grain to polished grain foods.Bran is the hard outer layer of cereal grains which accounts for 10%, rich in a myriad of phytochemicals with anticancer viz.phenolics, flavonoids, glucans and pigments, but it is discarded by by-product of milling process (Patel, 2012).There's a delicate balance of bioactive components in rice bran show anti-cancer activity, namely dietary rice bran may exert beneficial effects against breast, lung, liver, prostate, intestinal, and colorectal cancer (Verschoyle et al., 2007;Henderson et al., 2012).The low cost of rice production and the accessibility of rice bran make it an appealing candidate for global dietary chemoprevention (Henderson et al., 2012).Twelve sphingolipids from wheat bran extract showed little growth inhibition against human colon cancer cell lines in vitro (Zhu et al., 2013a).In whole wheat flour, the bran/germ fraction contributed 83% of total phenolic, 79% of total flavonoid, 78% of total zeaxanthin, 51% of total lutein, and 42% of total β-cryptoxanthin (Liu, 2007).High fiber diet prevents prostate cancer progression in early stages based on Asian and Western cultures (Raina et al., 2013).Therefore, whole grain and bran products promise potential applications as anticancer ingredients in functional foods.
Secondly, diet with low fresh vegetables is a major factor that cause cancers, especially the deficiency of malnutrition.There are anticancer for a lot of vitamins from vegetables but it is easily destroyed after cooking.Daily multivitamin supplementation modestly but significantly reduced the risk of total cancer (Gaziano et al., 2012).Vitamin B6 and riboflavin intakes from diet were associated with a decreased risk of colorectal, lung, breast cancer and so on (Zschäbitz et al., 2013).Higher concentrations of plasma carotenoids and lutein may reduce risk of urothelial cell carcinoma (Ros et al., 2012).Selenium (Se) and calcium (Ca) deficiency was associated with cancer risk, but higher Se supplementation as to be associated with lower cancer mortality (Jaworska-Bieniek et al., 2012), and a possible role for increasing dietary calcium intake in lung cancer prevention among female nonsmokers (Takata et al., 2012).Iron efficacy is recommended key steps in modern cancer patient management to minimise impact on quality of life and performance status (Aapro et al., 2012).Zinc level regulation dysfunction has been identified in prostate cancer cells and may thus play an important role in the prostate cancer pathogenesis (Gumulec et al., 2011).
Thirdly, unhealthy lifestyle for dietary is one major factor that causes cancers, such as tea at high temperature, alcohol, red meat, salt and so on.Up to now, approximation 1,000 reports have been published showing the potential of green tea polyphenols as cancer chemoprevention agents.On the contrary, drinking tea at high temperature in the South China increases risk of esophageal cancer (Chen et al., 2011).According to public data of State Statistical Bureau, alcohol yield of China in 2011 achieved 10.25 million t; Alcohol remains a major contributor to cancer mortality, but reducing alcohol consumption is an important cancer prevention strategy (Nelson et al., 2013).Vegetarians have lower risk of all cancers and gastrointestinal cancers than meat eaters (Tantamango-Bartley et al., 2013), but an high-fat diet enhanced prostate cancer cell growth more strongly than an high-carbohydrate diet or control diet (Huang et al., 2012a).China account for 92% of the world's total pig yield (109 million t) in 2011; Red meat consumption was associated with an increased risk of breast, colon and pancreatic cancer due to the presence of carcinogens in foods cooked at high temperatures (Ferguson et al., 2010;Larsson et al., 2012).The salt intake is an important dietary risk factor for gastric cancer (Peleteiro et al., 2011).
Fourth, obesity is one of factor that causes cancers, but the most cases of obesity is a combination of excessive food energy intake and a lack of physical activity.Common cancers studied in the context of obesity include colorectal, breast, prostate, endometrial, pancreatic, liver, ovarian, kidney, gallbladder, leukaemia, and oesophageal cancers; however, a associations between abnormal lipid components and risk of obesity-related cancers (Melvin et al., 2013).The body size, body shape, and weight gain during childhood or adolescencemay play a role in the risk of breast cancer (Amadou et al., 2013).

Cereals and cancer prevention
Cereal grains are the primary source of human food and animal feed globally (Xue et al., 2008) as well as cancer prevention.Whereas cereals (rice, barley, wheat) are the largest contributors of calories to the human diet, little is known about their role in cancer prevention.The consumption of whole grains has been associated with reduced risk of some cancers and cardiovascular disease as well as type 2 diabetes (Liu, 2007).Lunasin is a novel cancer preventive, anti-inflammatory and cholesterol-reducing peptide originally isolated from later found in cereals (barley, rye, wheat, triticale) (Nakurte et al., 2013).The oat 'Ivory' contained the highest and the most stable lunasin level (0.196 mg/g) DOI:http://dx.doi.org/10.7314/APJCP.2013APJCP. .14.3.1592Strategies of Functional Food for Cancer Prevention in Human Beings of grain (Nakurte et al., 2013).Fermentation by lactic acid bacteria of wholemeal wheat and barley as well as rye flours increased the concentration of lunasin with anticancer, which would suggest new possibilities for the formulation of functional foods (Rizzello et al., 2012).β-glucans belong to a group of polysaccharides located in the cell wall of bacteria, fungi including mushrooms, as well as cereals such as barley and oats, and their anticancer effects were demonstrated mainly in in vitro and in vivo experimental systems (Aleem, 2012).Wheat straw hold various bioactive compounds such as policosanols, phytosterols, phenolics, and triterpenoids, having enormous nutraceutical properties like anticancer, anti-inflammatory, anti-allergenic, antioxidant, antiartherogenic, anti-microbial, anti-thrombotic, antiviral, cardioprotective and vasodilatory effects (Pasha et al., 2013).
Rice (Oryza sativa L.) is one of the most important cereal for human nutrition (Huang et al., 2012b) and contributes 21% to human's nutrient intake and energy requirements.Asia account for 92% of the world's total rice production (6.78 million tonnes).Germinated brown rice is not only richer in the basic nutritional and bioactive components, but also become a popular functional food, which exhibits many physiological effects, including anticancer, antihypertension, antidiabetes etc. chronic diseases (Wu et al., 2013).The pigmented rice contains a variety of flavones, tannin, phenolics, sterols, tocols, γ-oryzanols, amino acids, GABA, and essential oils, which has a lots of bioactivities including antitumor, antioxidant, antiatherosclerosis, hypoglycemic, and antiallergic activities (Deng et al., 2013).There was a positive relationship between all phenolic and shikimic acids (Kim et al., 2013b).Rice bran is used for functional food with anticancer, based on bioactive phytochemicals such as ferulic acid, tricin, γ-oryzanol, β-sitosterol, tocotrienols/ tocopherols, and phytic acid (Henderson et al., 2012), meanwhile the anticancer activity of cycloartenyl ferulate in rice bran showed the most prominent in vitro growth inhibition on human colorectal adenocarcinoma SW480 (Kong et al., 2009).Total proanthocyanidin was the highest in red rice bran, while total anthocyanin was highest in purple brans (Min et al., 2011).The dietary rice bran may exert beneficial effects against several types of cancer, such as leukemia, breast, lung, liver, cervical, stomach,and colorectal cancer (Chen et al., 2012;Henderson et al., 2012).Red mold rice is always a functional food in Asian people, its extracts exhibits direct cytotoxic and proapoptotic effects on MCF-7 cells and could be considered as a potential functional food for breast cancer prevention (Lee et al., 2013).Rice husks should be further studied for use in health promotion products, the total phenolic content was related to the antioxidant activity and total fatty acid content (r = 0.997 and 0.864) in linoleic acid (r = 0.989) (Lourith et al., 2013).Therefore, dietary rice bran and brown rice have the potential to have a significant impact on cancer prevention for the global population.
Barley (Hordeum vulgare L.) is among the world's earliest domesticated and most important crop of functional food; Food and Drug Administration in USA permit a human health claim for cell-wall polysaccharides from barley grain (The International Barley Genome Sequencing Consortium, 2012).Barley grain is not only particularly high in soluble dietary fibre, which significantly reduces the risk of serious chronic diseases including colorectal cancers, type II diabetes, and cardiovascular disease (Collins et al., 2010), but also high contents of β-glucans, soluble non-starch polysaccharides, protein, and lower starch content, which could be suitable for functional food products aimed at cancer prevention (Holtekjølen et al., 2007).The content (mg/kg) of tocotrienols anti-cancer are in turn barley (910) >rice bran (465)> oat (210) > maize (200) > wheat germ oil (189) > rye (92) (Aggarwal et al., 2010).Germinated barley foodstuff has not only shown antitumor effects in a rat model of azoxymethane induced colon carcinogenesis (Kanauchi et al., 2008), but also effectively reduces the risk of colitic cancer, which prevents colitis-related dysplasia and inflammatory change in chronic and subacute colitis models by modulating the intestinal environment as a prebiotic (Komiyama et al., 2011).Hulless barley is a good source of β-glucan, arabinoxylans, phenolics, flavonoids, anthocyanins, vitamin E, lutein and zeaxanthin; lutein and zeaxanthin act together with other bioactive compounds against cancer effects (Siebenhandl-Ehn et al., 2011).Tsangpa with barley flour is regarded as a white medicine, one of the main reasons why heart disease and colon cancers occur at a lower rate in Tibet than that of expected (Nyima et al., 2012).Protocatechualdehyde is a polyphenol found in barley and so on, it possesses anticancer activity through suppression HDAC2-mediated cyclin D1 in human colorectal cancer cells (Jeong and Lee, 2013).Lunasin of a unique 43-amino acid peptide, contents of lunasin in braley grain is highest in cv.Salrok (99.0 µg/g), while cv.Nonghwa has the lowest (12.7 µg/g) and consumption of barley could play an important role of cancer prevention in barley-consuming populations (Jeong and Jeong, 2010).Barley grass powder holds promise to be used as a functional food to optimise the health of diabetic and cancer subjects (Venugopal and Iyer, 2010).Therefore, barley has the potential functional food on cancer prevention for the global population.
The cultivated common buckwheat originated from Yunnan-Eastern Tibet border area (Ohnishi, 2009).The wild ancestor of common buckwheat is F. esculentum ssp.ancestrale.F. homotropicum is interfertile with F. esculentum and the wild forms have a common distribution, in Yunnan; The wild ancestor of tartary buckwheat is F. tataricum ssp.potanini.(Ohnishi and Matsuoka, 1996).Many prophylactic compounds that are concentrated in outer layers of buckwheat grain, Bamby (0.41%) and KASHO-2 (0.36%) with high polyphenols displayed the best growth inhibitory activity on HeLa cancer cells (Danihelová et al., 2013).The red clover flavone from golden buckwheat can inhibit the migration ability of human gastric cancer SGC7901 cells (Zhang et al., 2013).

Vegetables and cancer prevention
Bitter melon (Momordica charantia) is widely consumed as a vegetable and medicine as well as functional food in the world.Superfine grinding and lyophilization are helpful for improving extraction of proteins, polysaccharides and other bioactive components such as total pholenols, flavonoids and saponins from bitter melon; Bitter melon lyophilized superfine grinding powder had higher total polyphenols of 10.03 mg/g and total flavonoids of 5.27 mg/g compared with its hot air drying superfine grinding powder (Zhu et al., 2013b), which rich in phenolics and have a strong antioxidant activity as well as a radical-scavenging action, meanwhile significant positive correlations (R 2 = 0.999) between total phenolics and antioxidant activities (Amira et al., 2013).In vivo, 1% and 5% bitter melon leaf extract in the diet resulted in 63% and 57% inhibition of human prostate cancer cell growth (Pitchakarn et al., 2012).The diet of bitter melon can be an effective preventive/therapeutic agent for prostate, breast, colon and adrenocortical cancer (Ray et al., 2010;Ru et al., 2011;Brennan et al., 2012;Kwatra et al., 2013).Therefore, bitter melon might have health benefits for consumers as a potential functional food.
Allium vegetables with aromatic properties can be used as a dietary for a lot of cancers prevention (oral, pharyngeal, esophageal, stomach, colorectal, laryngeal, breast, ovarian, prostate, and renal cell cancers) in Asia and Europe (Galeone et al., 2006); The reduced risk of prostate cancer associated with allium vegetables including garlic, onions, scallions, chives, and leeks (Hsing et al., 2002).Garlic and its derived compounds (diallyl trisulfide) are promising candidates for breast and skin and colorectal as well as prostate cancer prevention (Tsubura et al., 2011;Wang et al., 2012a).Onions (Allium cepa L.) might be useful for preventing obesity-related breast, colorectal, laryngeal, and ovarian cancers (Galeone et al., 2006;Wang et al., 2012b).Onions in China (20,507,759 t) and India (13,372,100 t) accounted for over 55% of world output in 2012 according to FAO.
Cruciferous vegetables (e.g., broccoli, cabbage, mustard greens, Brussels sprouts) have generated interest as dietary constituents that may protect against many cancer.Cabbage in China (25,156,578 t) accounting for over 43% of world output in 2010 according to FAO.Broccoli in China (8,585,000 t) and India (5,014,500t) accounting for over 71% of world output in 2009 according to FAO.The high intake of cruciferous vegetable (cabbage and broccoli) was inversely associated with the risk of colorectal and colon and prostate as well as bladder cancer in humans (Tang et al., 2010;Liu et al., 2012;Wu et al., 2013).After carefully controlling for cigarette smoking, higher intake of cruciferous vegetable was associated with lower risk of lung cancer (Lam et al., 2010).

Mushrooms and cancer prevention
Mushrooms have been used widely since ancient times as foods and medicinal as well as functional purposes.The antitumor effects of mushrooms included to breast cancer, colon cancer, gastic cancer, prostate cancer, pancreatic cancer, cervical and ovarian as well as endomentrial cancer (Roupas et al., 2012), those are primarily due to biopolymers (Lemieszek et al., 2013).Phellinus linteus is a well-known Oriental medicinal fungus with antitumor activities, which a dietary supplement extract may have potential use for the alternative treatment of cancer (Sliva, 2010).Six main constituents were isolated from mushroom Inonotus obliquus, thereinto ergosterol peroxide and trametenolic acid showed obviously cytotoxicity on human prostatic and breast carcinoma cell (Ma et al., 2013).PSP (an active component extracted from the mushroom Coriolus versicolor) may be an effective agent for prostate cancer chemoprevention (Luk et al., 2011); Coprinus comatus contains potent compounds capable of inhibiting NF-kappa B function and also possibly acts as an antitumor agent (Asatiani et al., 2011).The identification of the molecular mechanisms by which maitake (D fraction) mushroom exerts its effects is crucial for the development of preventive and therapeutic strategies for breast cancer (Soares et al., 2011).Some countries use mushroom isolates lentinan, PSK, PSP, irofulven, and acylfulvene as anticancer immunologic adjuvants.Therefore, the bioactive compounds from mushrooms against cancer raises global interest.
Many of the boletes are considered to be true delicacies, especially the king bolete (Boletus edulis).The Sun went dim early that morning on the 24 June 2026, Boletus edulis will be released to start production of the population alive around the world (Meikle, 2012).The lectin and a biopolymer BE3 from Boletus edulis possess anti-proliferative effects and anticancer potential, which may provide a new therapeutic/preventive option in cancer chemoprevention (Bovi et al., 2012;Lemieszek et al., 2013).Boletus regius was the species with the highest antioxidant activity of carbohydrates (88.79 g/100 g) and PUFA (56.55%), tocopherols (763.80 μg/100 g), citric acid (3.32 g/100 g) and phenolic compounds (23.49mg/100 g) (Leal et al., 2013).The three new fatty acid esters showed significant inhibitory activity against the proliferation of the tested cancer cell lines with IC (50) values in the range 2.77-12.51μM (Kim et al. 2012a).Boletus edulis could be incorporated directly in diet acting as functional foods of anticancer.
Tricholoma matsutake has been regarded as famous foods and biopharmaceutical materials with a great deal of interest (Tong et al., 2012).Southwestern China is a region where over 25% of the global T. matsutake harvest (Xu et al., 2008).Tricholoma matsutake has been used as a vegetable and a traditional Chinese medicine for the prevention and treatment of disease for several thousand years (Ding et al., 2010).Tricholoma matsutake is potential anticancer drug candidates for oral cancer, based on it induce apoptosis to inhibit tumor growth of HSC-2 cells by modulating the Bak protein (Shin et al., 2012).Two polysaccharides were isolated from this mushroom, MTS-1 was composed of glucose, xylose, galactose in a molar ratio of 12.89:1.20:1and MTS-2 consisted of glucose (Wang et al., 2012c).The extraction rate of polysaccharides from Tricholoma matsutake could reach 18.43%-21.63%,the polysaccharides presented significant antitumor activity against B16 human melanoma cells in vitro in a dose-dependent manner (Yang et al., 2010).

Beverages crop and cancer prevention
Tea is derived from the leaf of Camellia sinensis, DOI:http://dx.doi.org/10.7314/APJCP.2013.14.3.1592 Strategies of Functional Food for Cancer Prevention in Human Beings the second most popular beverage in the world.Tea is cultivated in Asia producing more than 91% of the world (Shi et al., 2012).The world evoked the interest of its use in cancer prevention based on green tea polyphenols with strong antioxidants and the inhibition of carcinogenesis, e.g. esophageal, stomach, bladder, kidney, urinary tract, colon, rectum, uterus, prostate, liver, lung, breast, pancreas, and skin cancer (Shukla, 2007).The most active polyphenol in green tea is epigallocatechin gallate, it's regular drinkers demonstrated a 40% reduction in breast, prostate and ovarian cancer risk (Ogunleye et al., 2010).The 30-40% polyphenols of green tea decreased risks of ovarian, breast, prostate, gastric, colorectal cancers, and adult leukemia in Chinese populations (Shi et al., 2012;Zhang et al., 2012).
Consumption of coffee is associated with a reduced risk of liver cancer (Larsson and Wolk, 2007).Caffeinated coffee intake was inversely associated with oral/ pharyngeal cancer mortality (Hildebrand et al., 2013).

Functional Food and Chronic Diseases
Southwest China (especially Yunnan Province) is not only the center of origins and evolution for functional crop (Asian cultivated rice, buckwheat, single clove garlic, mushrooms, tea and so on) (Wang et al., 2007;Zeng et al., 2007;Huang et al., 2012b;Shi et al., 2012), but also one of the centers of the origin for ancient human (Curnoe et al., 2012;Zeng et al., 2012a).The morphology sampled at Longlin Cave (Guangxi Province) and Maludong (Yunnan Province) of Southwest China may represent a paralleling the situation seen in North Africa as indicated by remains from Dar-es-Soltane and Temara, based on ancient mtDNA and Y-DNA lineages, and has yielded a number of human remains thought to derive from Pleistocene deposits (Curnoe et al., 2012).
Rice originates from a single domestication 8,200-13,500 years ago (Molina et al., 2011), in the Pearl River valley region of China (Huang et al., 2012b).The dietary rice bran and brown rice have not only the potential to a significant impact on cancer and hypertension (Zeng et al., 2011) and diabetes prevention (Zeng et al., 2012) for the global population, but also be similar to traditional Chinese medicine, further support that Yunnan in China is one common sphere that the origins of human evolution is closely related to the origin of rice evolution (Zeng et al., 2012).Garlic (Allium sativum) has been playing one of the most important dietary and anticaner roles in human beings (Kim et al., 2013a); Single clove garlic originated Yunnan province of China.Garlic in China (13,664,069 t) accounting for over 99% of world output in 2010 according to UN Food & Agriculture Organisation (FAO).There are 220 species with antitumour active components of 882 species mushrooms in Yunnan Province of China (Zhang, 2007).The value of export for boletes and Tricholoma matsutake with anticancer from Yunnan Province in China is up to 91.78 million USD and 57.38 million USD in 2011.Camellia sinensis originated from Yunnan Province in China, Yunnan has 22 species and 3 varieties, which accounting for 73.5% of Camellia sinensis in the world (Wang et al., 2007).There are more than 500 compounds identifyed, tea in Yunnan has 15 accessions for 35.0%-46.8%polyphenols, 14 accessions over 5% caffeine (Wang et al., 2007).This article's results validate above-mentioned that functional food crop (brown rice, buckwheat, garlic, mushrooms, tea and so on) for cancer prevention is not only similar to hypertension (Zeng et al., 2011) and diabetes prevention (Zeng et al., 2012) in China and in the world, but also further support that Southwest China (especially Yunnan Province) is one common sphere that the origin of functional crop evolution is closely related to the origins and chronic diseases of human evolution.

Conclusions and Future Prospects
Major cancer risk factors for dietary substances in human being are whole grain to polished grain foods for dietary, low fresh vegetables, unhealthy lifestyle and obesity.The strategies of cancer prevention in human being are the functional food with whole grains and its by-product (brown rice, rice bran, barley grass powder, wholemeal wheat and barley, buckwheat), some vegetables (bitter melon, garlic, onions, cabbage, broccoli and so on) and mushrooms (boletes, Tricholoma matsutake and so on) as well as beverages crop (green tea and coffee) for dietary.This article's results offer insight into further Southwest China (especially Yunnan Province) is one common sphere that the origin of functional crop evolution is closely related to the origins and chronic diseases of human evolution.We hope that this type of study will open new areas of research for functional food and cancer prevention in the world.Our goal is to establish one research center of functional foods is closely related to chronic diseases prevention of human being.