Saturday, 25 January 2014

Phytochemical Allicin as antioxidants

Allicin is phytochemical containing sulfur in the class of organosulfur compound, found abundantly in onion and garlic.
A free radical is any atom or molecule that has a single unpaired electron in an outer shell and highly reactive to react with other cell, which in turn, causes oxidative damage to the enzymes, other protein, unsaturated fatty acid, phospho-lipids, DNA and RNA, etc., leading to aging of the organisms, as a result of widespread damage due to set of a chain reaction auto-catalytically after attacking the lipid bilayers of the cell walls. 

The health benefits
Beside with protective effect against development of certain diseases, allicin found in garlic and onion may also be an antioxidant scarvenger of oxygen free radicals (OFRs). Study of hydroxyl radicals (.OH), indicated the prevention of allicin effect in lipid peroxidation of malondialdehyde in liver homogenate in a concentration-dependent manner. Other in the study of the hydroxyl scavengers of allyl cysteine, alliin, allicin, and allyl disulfide, showed allicin did not exhibit hydroxyl radical scavenging but antioxidant activities as protective compounds against free radical damage.


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References
(1) Antioxidant activity of allicin, an active principle in garlic by Prasad K, Laxdal VA, Yu M, Raney BL.(PubMed)
(2) The antioxidant properties of garlic compounds: allyl cysteine, alliin, allicin, and allyl disulfide by Chung LY.(PubMed)

Herbal Cascara Sagrada (Rhamnus purshiana) and type 2 diabetes

Cascara sagrada is a species of buckthorn, genus Rhamnus, belonging to the family Rhamnaceae, native to western North America, it's bark has been used in traditional medicine for gastrointestinal support. and it is thought to have a laxative and natural cleansing, etc.,
Diabetes is defined as a condition caused by insufficient insulin entering the bloodstream to regulate the glucose. It is either caused by cells in pancreas dying off or receptor sites clogged up by fat and cholesterol. In some cases, diabetes is also caused by allergic reactions of cells in the immune system.
The Ingredients
The chemical constituents of Cascara Sagrada include Aloe-emodin, Anthrquinone glycosides (Barbaloin Cascarosides A, B, C and D ChrysaloinFrangul), Chrysophanol, Emodin, Heterodianthrones palmidin A, B, and C, dianthrones, Oxanthrone, Rhein, Tannins, etc.

The benefits
Emodin, a natural component of Cascara Sagrada, beside stimulates  AMP-activated kinase (AMPK) activity in skeletal muscle and liver cells, but is found to be effective in treating insulin sensitivity by regulating the glucose homeostasis, by AMPK activation of that the component may represent a novel therapeutic principle in the treatment of type 2 diabetic models. The Tsinghua University and Shanghai Institute of Materia Medica in the study of emodin also support the use of emodin in treating diabetes and metabolic syndrome


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References
(1) Emodin regulates glucose utilization by activating AMP-activated protein kinase by Song P, Kim JH, Ghim J, Yoon JH, Lee A, Kwon Y, Hyun H, Moon HY, Choi HS, Berggren PO, Suh PG, Ryu SH.(PubMed)
(2) Promotion of adiponectin multimerization by emodin: a novel AMPK activator with PPARγ-agonist activity by Chen Z, Zhang L, Yi J, Yang Z, Zhang Z, Li Z.(PubMed)
(3) Emodin, a natural product, selectively inhibits 11beta-hydroxysteroid dehydrogenase type 1 and ameliorates metabolic disorder in diet-induced obese mice by Feng Y, Huang SL, Dou W, Zhang S, Chen JH, Shen Y, Shen JH, Leng Y.(PubMed)

Phytochemical Piperine and cognitive impairment

Piperine is a phytochemical alkaloid in the class of organosulfur compound, found abundantly in white and black pepper, long pepper, etc.
Cognition is the process of the brain including the attention of working memory, producing and comprehending language, learning, reasoning, problem solving, and decision making.

The health benefits
In chronic unpredictable stress (CUS)-induced cognitive impairment and oxidative stress in mice,
Piperine showed to potentiate the protective effects of curcumin in significantly improved behavioral and biochemical alterations, restored mitochondrial enzyme complex activities and attenuated increased acetylcholinesterase and serum corticosterone levels. In olfactory bulbectomy induced depression in rats, co-administration of piperine with curcumin significantly potentiated the effects in behavioral, biochemical, mitochondrial, molecular and histopathological alterations. These potentiation of co administration also showed  to prevented all the behavioral, cellular, and neurochemical changes associated with the chronic administration of haloperidol, as compared to their effects alone.


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References

(1) iperine potentiates the protective effects of curcumin against chronic unpredictable stress-induced cognitive impairment and oxidative damage in mice by Rinwa P, Kumar A.(PubMed)
(2) Suppression of neuroinflammatory and apoptotic signaling cascade by curcumin alone and in combination with piperine in rat model of olfactory bulbectomy induced depression.

Rinwa P, Kumar A, Garg S.(PubMed)
(3) Protective effect of curcumin and its combination with piperine (bioavailability enhancer) against haloperidol-associated neurotoxicity: cellular and neurochemical evidence by Bishnoi M, Chopra K, Rongzhu L, Kulkarni SK.(PubMed)
 

Phytochemical Phytic acid and Diabetes

Phytic acid (Inositol hexaphosphate) are phytichemicasl of the organic acid found abundantly in nuts, sesame seeds, soybeans, wheat, pumpkin, beans, almonds, etc.
Diabetes is defined as a condition caused by insufficient insulin entering the bloodstream to regulate the glucose. It is either caused by cells in pancreas dying off or receptor sites clogged up by fat and cholesterol. In some cases, diabetes is also caused by allergic reactions of cells in the immune system.

The benefits
In streptozotocin-induced diabetic rats, fed with or without phytic acid supplementation for thirty days, showed a positive effects in lowering spike in random blood glucose, in the same group, serum triglycerides and increased total cholesterol and HDL was also reduced. On the levels of blood glucose and some enzymes of carbohydrate and lipid metabolism with rats fed formulated diets supplemented with zinc or without zinc, formulated diets supplemented with zinc plus phytic acid extracted from sweet potato (Ipomea batatas) or commercial phytic acid respectively, showed a lowered blood glucose levels in Phytic acid extract consumption from sweet potato and commercial phytic acid plus zinc supplement. These results may indicted that the use of sweet potato diet in diabetic management.



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References
(1) The potential benefits and adverse effects of phytic Acid supplement in streptozotocin-induced diabetic rats by Omoruyi FO1, Budiaman A1, Eng Y1, Olumese FE2, Hoesel JL3, Ejilemele A3, Okorodudu AO (PubMed)
(2) The effect of phytic acid on the levels of blood glucose and some enzymes of carbohydrate and lipid metabolism by Dilworth LL, Omoruyi FO, Simon OR, Morrison EY, Asemota HN(PubMed)

Phytyochemical Anacardic acid and anti microbal activity

Anacardic acids are phenolic lipids, phytochemicals of the organic acid found abundantly in cashews, mangoes, etc.
The immune system is the set of cells and their activity against antigens or infectious agents that comprises of the body's defense system against diseases. The immune system does a great job of keeping people healthy and preventing infections. Beside foods and nutritional supplements, herbs also play a important role in helping the immune system defend against viruses and bacteria attacks.

The health effects
An anacardic acids mixture isolated from Amphipterygium adstringens has performed its anti bacterial effect as an alternate to antibiotics by inhibition of the regulator of virulence and biofilm formation in the pathogenic bacteria Pseudomonas aeruginosa. Anacardic acid mixture (AAM) showed 94% of inhibition of the violecin production at 166 μg/mL and 86% of inhibition of pyocyanin production  at 200 μg/mL). Otehr in the study of a new anacardic acid, indicated that its deviratives, 16'Z-nonadecenyl]-salicylic acid and masticadienonic acid also inhibited bacterial activity against Streptococcus mutans and Porphyromonas gingivalis with minimum inhibitory concentrations.



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References
(1) Amphypterygium adstringens anacardic acid mixture inhibits quorum sensing-controlled virulence factors of Chromobacterium violaceum and Pseudomonas aeruginosa by Castillo-Juárez I, García-Contreras R, Velázquez-Guadarrama N, Soto-Hernández M, Martínez-Vázquez M. (PubMed)
(2) Isolation of the new anacardic acid 6-[16'Z-nonadecenyl]-salicylic acid and evaluation of its antimicrobial activity against Streptococcus mutans and Porphyromonas gingivalis by Rivero-Cruz BE, Esturau N, Sánchez-Nieto S, Romero I, Castillo-Juárez I, Rivero-Cruz JF.(PubMed)

Herbal Cascara Sagrada and (Mastitis) inflammation of breast tissue

Cascara sagrada is a species of buckthorn, genus Rhamnus, belonging to the family Rhamnaceae, native to western North America, it's bark has been used in traditional medicine for gastrointestinal support. and it is thought to have a laxative and natural cleansing, etc., effect.
Mastitis is the  inflammation of breast tissue, mostly caused by Staphylococcus aureus

The ingredients
Beside the main compound of anthraquinones, otyher compounds include anthraquinone glycosides, (emodin, frangulin, iso-emodin, aloe-emodin, and chrysophanol), rhein, aloin, malic acid, tannic acid, cascarosides A, B, C, and D, and hydroxy anthracene derivatives (HAD), etc.

The effects
Nanosilver particles (AAgNPs), a derivative of chemical constituent of aloin found in Cascara Sagrada may be the protential target used as antibiotics for treatment of infectious and inflammatory diseases, including mastitis. In the Staphylococcus aureus induced murine mastitis study of a total of 40 female mice were divided into five groups of eight animals each, Nanosilver particles (AAgNPs) is found to be effective (concentration of 21.8) than antibiotic as it exerted the anti inflammatory activity in reducing white blood cell (poly-morpho nuclear cell) infiltration.Other chemical compound emodin found in the herb, in a study of of the same but with  lipopolysaccharide (LPS)-induced mastitis also found to significantly reduced infiltration of neutrophilic granulocyte. These result may be given the green light for the chemical compounds of Cascara Sagrada used as a novel treatment strategy for mastitis.

The Side effects
1. Cascara Sagrada can be liver toxic.
2. It may cause Postal hypertension
Cascara sagrada (CS) has been associated with the development of cholestatic hepatitis, complicated by portal hypertension.
3. Fresh cut, dried bark may cause vomiting and diarrhea.
4. It may allergic effect.
5. Etc.


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References
(1) Emodin ameliorates lipopolysaccharide-induced mastitis in mice by inhibiting activation of NF-κB and MAPKs signal pathways by Li D, Zhang N, Cao Y, Zhang W, Su G, Sun Y, Liu Z, Li F, Liang D, Liu B, Guo M, Fu Y, Zhang X, Yang Z.(PubMed)
(2) Evaluation of therapeutic potential of nanosilver particles synthesised using aloin in experimental murine mastitis model by Chaitanya Kumar TV, Muralidhar Y, Prasad PE, Prasad TN, Alpha Raj M.(PubMed)

Friday, 24 January 2014

Breast cancer - In foods' Points of View

 Kyle J. Norton

The prevalence of breast cancer has been acknowledged in the scientific community worldwide. Breast cancer widespread in women in Southeast Asian as a result of over 2 decades of economic prosperity caused by unhealthy diet is a major concern. The findings for effective treatments are ongoing with some successes, but to discover an effective prevention and treatment with little or no side effects has proven difficultly. According to statistic, the risk of getting invasive breast cancer during life time of a women is 1/8.. Detections of tumorigenesis through self observation are still the best approach to cure breast cancer in early stage but reduction of the mortality has not been accounted even with extensively modern technology in the field of diagnosis and insurance protection in Western world, needless to say of counties which have little. Emerged suggestions of healthy diet with plenty vegetables and fruits(1)(2)(3) with change of life style(4)(5)(6) may be the only choice for women in reducing risk of the diseases.
In fact, certain vegetables(7)(8) and fruits(9)(10) or chemical compounds in them have been found to effect the breast cancer lines, induced apoptosis of breast cancer cells by blocking the energy sources of the pathways, influencing the signal pathways of the proliferation of the cells or suppressing the  promoted cancers genes.
I. Types of vegetables may reduce risk of breast cancer
A. Cruciferous vegetables
Cruciferous vegetables are the group of  vegetables belonging to the family Brassicaceae, including cauliflower, cabbage, cress, bok choy, broccoli etc.
Isothiocyanate (ITC), one of the major chemical constistuent found in Cruciferous vegetables has been studied extensively over the past three decades with preclinical evidence for the efficacy of various ITCs against cancer in preclinical models. Benzyl isothiocyanate, the derivative of  isothiocyanate showed an effectiveness in influencing carcinogen metabolism and signaling pathways relevant to tumor progression and invasion(11) against MDA-MB-231(breast cancer dell line), human breast cancer xenografts(mutation tissues)(12), suppressing X-linked inhibitor of apoptosis (XIAP) protein expression of cancer cell line MCF-7 by knockdown of the p53(antigens) protein level(13).
In Her-2 positive (a most aggressive case of breast cancer), indole-3-carbinol, a naturally occurring compound found in cruciferous vegetables, used combination with paclitaxel (a mitotic inhibitor) synergistically inhibited growth of Her2/neu human breast cancer cells by arresting cancer cells in the G2(pre-mitotic phase) and M(nuclear division) phase and inducting apoptosis/necrosis(14). I3C used alone also inhibited Her-2breast cancer cell growth in a dose dependent manner as the compound up-regulated Bax(an apoptosis promoter), down-regulated Bcl-2(an apoptosis inhibitor) and, thereby, increased the ratio of Bax to Bcl-2 favoring apoptosis(15).

2. Tomatos
Tomato is a red, edible fruit, genus Solanum, belonging to family Solanaceae, native to South America. Because of its health benefits, tomato is grown world wide for commercial purpose and often in green house.
Lycopene, a major carotenoid component of tomato has been known in research community with the property to attenuate the risk of breast cancer. In a time and doses depended, the compound showed an anti-proliferative activity against ER(estrogen receptor)/PR(progesterone receptor) positive MCF-7, HER2-positive SK-BR-3 and triple-negative MDA-MB-468 cell lines by arresting cell cycle at the G0 /G1 phase(interphase together - chromosomes replicate in preparation for cell division) at physiologically achievable concentrations(range) found in human plasma(16) and Inhibition of the  ER-positive MCF-7 through the cell cycle progression, ER-negative MDA-MB-231 cells through G1 phase cell cycle-arrest as well as apoptosis(17). There is a report of  a lack of GSTP1 expression in untreated MDA-MB-468. Lycopene treatment not only restored the GSTP1 expression but also with 2 microM, once per week for 2 weeks induced demethylation of RARbeta2 (tumor suppressor gene) and the HIN-1(a cell growth inhibitor)) genes in the noncancer MCF10A fibrocystic breast cells(18).

3. Figs
N-hexane insoluble fraction (HIF) found in figs may be lesser known for its efficacy in breast cancer cell suppressive activity. The combination of HIF and doxorubicin showed a greater inhibition on cell growth in (Human ductal breast epithelial tumor cell line) T47D cells  and increased the incidence of cells undergoing apoptosis, when compared to exhibited doxorubicin alone(19). The soluble fraction (Ethyl acetate soluble fraction (EASF)) in fig leave was also found to enhance the cytotoxic effect of doxorubicin by changing the inhibition of cell cycle G(2)/M to G(1) phase(20) and Acetone extract of Ficus religosa leaf (FAE)  exerted its efficacy in irreversible inhibition of breast cancer cell growth with moderate toxicity by stimulating the loss of mitochondrial membrane potential in multiple breast cancer cell lines and accelerated cell death through the photosensitizing effect(21).

4. Garlic
Garlic is a natural superfood healer for its natural antibiotic with antiviral, antifungal, anticoagulant and antiseptic properties.
Diallyl trisulfide(DAS), a derived organosulfur compounds (OSCs) suppressed the a ratio of viable cells in the culture of (Human breast cancer cell line) MCF-7 and MCF-12a (a non-tumorigenic epithelial cell line) cells respectively by decreasing the percent of cells in phase G(2)/M and inducing apoptotic cell death as a result of up regulating Bax protein and p53(cellular tumor antigen) protein expression(22). DAS also enhanced the effect of eicosapentaenoic acid, a breast cancer suppressor, and decreased the effect of linoleic acid, a breast cancer enhancer and reduced the side effects caused by anti-cancer agents(23). In the study of a protein fraction from garlic, the fraction was found to be more effective than the augment CD8(+) T-cell infiltration into the tumor site, in inhibiting tumor growth more efficiently than garlic extract in enhancing the CD8(+) T-cell infiltration into the tumor site(24).

5. Spinach
Spinach is an edible flowering plant in the genus Spinacia, belonging to the family of Amaranthaceae and native to central and southwestern Asia. It is considered as a healthy plant containing vary vitamins and minerals.
Consuming spinach may be a significantly protective effect on breast cancer among premenopausal women(25). Eating carrots or spinach more than twice weekly, compared with no intake, was associated with an odds ratio of 0.56 (95% confidence interval 0.34-0.91), but does not distinguish among several potential explanations for the protective association observed between intake of carrots and spinach and risk of breast cancer.(26). It is said that included supplementation of A. gangeticus aqueous extract  of red spinach in 5%, 7.5% and 10% in cancer induced rats showed a induction of all tumor marker enzymes especially at 10%.(27).

6. Kelp
Kelps are large seaweeds (algae) growth under shallow in underwater of shallow oceans belonging to the class Phaeophyceae in the order Laminariales, with the thallus is used for food in many cultures. Laminaria, a brown kelp seaweed containing a antibiotic substance, 1-3 beta glucan, was effective in stimulating the host-mediated immune response and suggested of playing a essential role in preventing  the initiation of breast cancer(28). Japanese seaweed (Laminaria angustata) extracts was also found to exert its antimutagenic effects in certain breast and colon carcinogen(29). L-tryptophana substances isolated from the kelp rhizoid, may play an important role in in the inhibition of cell proliferation as an suggestion of increased tryptophan degradation occurred in women with early-stage breast cancer(30)(31).

7. Chili peppers
Chili pepper is the fruit of plants from the genus Capsicum, belonging to the nightshade family, Solanaceae. The fruit has been used in human history for spices and cultivated for commercial profits.
Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), a chemical constituent of chili peppers used in many cultures as anti cancer agent was found to inhibit the growth of ER-positive (MCF-7, T47D, BT-474) and ER-negative (SKBR-3, MDA-MB231) breast cancer cell lines, reducing 50% the size of MDA-MB231 breast cancer tumors(32), inducing cellular apoptosis through a caspase-independent pathway in MCF-7 cells(33). In the comparison of capsaicin and Dohevanil, synthesized from DHA and vanillylamine (precursor to capsaicin), researchers showed that the exhibited effects of both vanilloids and dohevanil  in growth inhibition and DNA fragmentation induction in MCF-7 cells, but dohevanil was more potent than capsaicin(34).
 
8. Carrot
Carrot can grow to 3ft tall. It is root vegetable with orange color normally, a sub spices of Daucus carota, belongs to the family Apiaceae, native to Asian and Europe.
Intake of cruciferous vegetable and carrot are inversely associations with risk of estrogen receptor-negative/progesterone receptor-negative breast cancer(35). Wild carrot or Daucus carota L. ssp. carota (Apiacea) oil extract, used in traditional medicine in Lebanon and in different regions throughout the world  was found to inhibit human colon (HT-29, Caco-2) and breast (MCF-7, MDA-MB-231) cancer cell lines, causing significant increase in cell death and decrease in cell proliferation(36).

B. Types of fruit may reduced risk of breast cancer 
1. Blueberry 
Blueberry is a flower plant, belonging to the family Eriaceae and native to Northern America. It can grows from 10 cm to 4 metres tall.
Triple-negative breast cancer TNBC, a cancer does not express the genes for estrogen receptor (ER),  progesterone receptor(PR), and HER2(gene) affecting approximately 15% of all caner cases. Female MDA-MB-231 tumor-bearing mice fed with high fat diet with 5% whole blueberry powder (BB), showed an inhibited TNBC and TNBC-related metastasis by reducing inflammation via specific cytokine-driven pathways with generation of an immune response to reduce tumor growth and metastasis(40). In 17β-estradiol-mediated mammary tumorigenesis,  5% blueberry diet, showed to reduce tumor volume and multiplicity significantly, by down regulation of CYP 1A1(enzymes, able to activate compounds with carcinogenic properties) and ER-α (a  receptor activated by the sex hormone estrogen)genes expression and also favorable modulation of microRNA (mir-18a and mir-34c) levels in gene regulation(41). Other chemical constituents anthocyanin and an anthocyanin-pyruvic acid adduct extract of blueberry were found to inhibited cancer cell proliferation by acting as cell antiinvasive factors and chemoinhibitors(42).

2. Avocado
Avocados are a commercially valuable fruit and are cultivated in tropical climates throughout the world, it is a green-skinned, pear-shaped fruit that ripens after harvesting and native to the Caribbean, Mexico, South America and Central America, belonging to the flowering plant family Lauraceous.
It is suggested that avocado-produced toxin persin may contain a positive anti breast cancer effect(43), Persin selectively induces a G2-M cell cycle arrest and cell death through caspase-dependent pathway(44). Others in the study of the same, persin showed a anti breast  cancer effect in both   estrogen receptor (ER) and ER-negative breast cancer cells(45).

3. Strawberry
Strawberries is a genius of Fragaria × ananassa belonging to the family Roseaceae. They have been grown all over the world with suitable climate for commercial profits and for health benefits.
Methanolic extract of strawberry (MESB) fruits showed to induced cytotoxicity in cancer cells, irrespective of origin, in a concentration- and time-dependent manner, in the testing against leukaemia (CEM) and breast cancer (T47D) cell lines through Induction of intrinsic pathway of apoptosis by activating p73 (a tumor suppressor) in breast cancer cells, when tumor suppressor gene p53 was mutated(46). Polyphenols, a major chemical component found in strawberry, as an extract,  induced cytotoxic with doses of approximately 50 microg/ml, causing a 50% reduction in cell survival in both the normal and the tumour lines, including (MCF-7) breast cancer cell lines(47). In other study, freeze-dried fruits of two strawberry cultivars ethanol extract, strongly inhibited CaSki and SiHa cervical cancer cell lines and MCF-7 and T47-D breast cancer cell lines(48).

4. Pomegranate
Pomegranate is a fruit-bearing small tree, genus Punica, belonging to family Lythraceae, native to Iran but has been cultivated in Asian since ancient time.
Pomegranate extracts and genistein were found to exert their anti cancer effect in growth inhibition of cell proliferation and induction of apoptosis in human breast cancer cells(MCF-7) in doses and time depending manner(49) by downregulated HR genes (a ubiquitous cellular pathway that mediates transfer of genetic information) and increased expression of microRNAs (miRNAs), miR-183 (predicted target RAD50) and miR-24 (regulation of gene expression)(50). Pomegranate fruit extracts (PFEs), in dose-dependent inhibited NF-kB-dependent reporter gene responses associated with proliferation, invasion, and motility in aggressive breast cancer phenotypes while decreasing RhoC and RhoA protein expression as these genes are associated with tumor cell invasion and metastasis(51).

6. Grapes 
Resveratrol, a polyphenolic compound known as a good chemopreventive agent for inhibiting carcinogenesis processes that target the regulators of cell function and DNA replication, found abundantly in grapes, berries and peanuts are associated to reduced risk of breast caner. HS-1793, a synthetic version of the compound induced G2/M(DNA damage checkpoint) arrest in the cell cycle progression in both types of cells and involved in cell-cycle arrest and probably in induction of p53(tumor suppressor gene)-dependent apoptosis in MCF-7 cells(52). Catechin (RQC), a polyphenol, was found to be effective in inhibiting mammary tumor growth and metastasis, by reduced Akt(multiple cellular processes activity, induced the activation of AMPK(cellular energy), and inhibited mTOR(mediate cellular responses) signaling in breast cancer cells(53). In Her-2 breast cancer, fox grape seed extract increased the expression of Bax(an apoptosis promoter) and AIF(Apoptosis inducing factor), and decreased total PARP(cellular processes) expression, leading to significant downregulation of Her-2 in MCF-7 cells(54).

7. Pineapple
Pineapple is a species of Ananas Comos, belonging to the family Bromeliaceae and native to southern Brazil and Paraguay. Today it is widely cultivated for commercial uses. Its rich of vitamins and mineral and digesting enzyme bromelin seems to help digestion after a high protein meal. It is a second only to banana as America's most favourite tropical fruit.
Bromelain, a major chemical constituent or  herb used in traditional medicine found in pineapple has exerted its anti-metastasis of breast cancer by up regulating the function of c-Jun N-terminal kinase in cell proliferation, differentiation, survival and migration and p38 kinase to cause programmed cell death(56). In GI-101A breast cancer cells, bromelain induced cell death via activation of the apoptosis mechanism, in increased dose-dependent by promoting apoptosis and cytokine processing of caspase-9 and caspase-3 coinciding with elevation of serum CK18 levels(56). In the brMDA-MB-231 mammary carcinoma, oral administration of bromelain increased the reduced bMAK- and MAK-cell activity in cell cycle regulation from 7.8% to 54% (bMAK-cell activity) and from 16% to 47% (MAK-cell activity by stimulating the deficient monocytic cellular cytotoxicity of mammary tumor(57).

8. Apple
Apple is the pomaceous fruit of the apple tree, a species of the rose family Rosaceae. It is one of the most widely cultivated tree fruits originated in Central Asia.
In estrogen-dependent MCF-7 and estrogen-independent MDA-MB-231 breast cancer cell lines, apple phytochemical extracts significantly inhibited cell proliferation in a dose-dependent manner and cell cycle modulation(58). In breast carcinoma Mcf-7 and Mcf-7:Her18 cells, peels of apple was found to be effective in antiproliferation  accompanied by a G0-G1 phase arrest in cell cycle of breast cancer cells by a tumor suppressor protein that suppressed the regulation of cell invasion, metastasis, and angiogenesis(59). Study of apple extracts and quercetin 3-beta-d-glucoside combination, also showed to possess the synergistic effect in MCF-7 cell proliferation(60).

9. Orange
Orange is a species of Citrus Sinensis, belonging to the family Rutaceae and native to the Southeast Asia. Orange is round citrus fruits with finely-textured skins, orange in color and one of most popular fruits in the world.
Polymethoxyflavones (PMFs), a chemical compound found in Sweet orange (Citrus sinensis L.) peel, showed to induce Ca(2+)-mediated apoptosis in human breast cancer cells by induced proapoptotic activity(61). D-limonene, another compound in orange peel oil, in rodent studies, also exhibited its chemotherapeutic activity against mammary cells, through the induction of tumor cell apoptosis, tumor redifferentiation, and/or suppression of key proteins of cell growth-regulating (62).

C. Others
1.  Black Rice
Black Rice is a type of rice with enriched Anthocyanins. including Indonesian black rice and Thai jasmine black rice. It has been considered as one of nature super foods with vary antioxidants.
Anthocyanins in black rice, with oral administration of AEBR (100 mg/kg/day) to BALB/c nude mice bearing MDA-MB-453 cell xenografts significantly suppressed tumor growth and angiogenesis by suppressing the expression of the physiological process factors MMP-9MMP-2( enzymes involved in the breakdown of extracellular matrix), and uPA(activator) in tumor tissue. Altogether, this study suggests the anticancer effects of AEBR against human breast cancer cells by inducing apoptosis and suppressing angiogenesis(37)(38). Other chemical constituents of species of black glumed’ Njavara (Oryza sativa L.) isolation, namely, flavonolignans, tricin 4'-O-(erythro-β-guaiacylglyceryl) ether (compound 1) and tricin 4'-O-(threo-β-guaiacylglyceryl) ether (compound 2), were also found to exert its effect on  breast cancer cell line MCF-7, causing apoptosis at concentration 40 and 30 μg/ by decreasing protein in the mitochondrial membrane, leading to chromatin condensation(39).

2. Green tea
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world.
As suggestions, regular green tea intake has been associated with an inverse risk of breast cancer, as  green tea enhanced  the production of Ki-67, a cancer antigen when compare to women who do not.(63). (-)-epigallocatechin gallate, a phytochemical in green tea was found to exert its epigenetic effects in altering the DNA methyltransferase expression in many types of cancer, including breast cancer(64). Catechins, another phytochemical of green tea, inhibited proliferation of breast cancer cells and blocked carcinogenesis in breast cancer probably through the expression of translocation across membranes or for degradation, ribonucleoprotein DNA reduplication, apoptotic cascade, etc.(65). In inflammatory breast cancer, a most aggressive type of breast cancer, green tea polyphenol epigallocatechin-3-gallate (EGCG), showed decreased expression of genes that promote proliferation, migration, invasion, and survival in human breast cancer cell lines, SUM-149 and SUM-190 by reduced lymphangiogenesis-promoting genes(66) and inhibited the cell proliferation at 72 hours, after 10 microM of EGCG treatment. These suggested a possible reactivation of apoptosis, may be through the complexity of the angiogenic switch leading to the modulation of the cell migration processes against triple negative breast cancer cells(67). In human breast cancer MCF-7 cells, selenium containing polysaccharides (Se-GTPs) from a new variety of selenium-enriched Ziyang green tea, in dose-dependent, exhibited an effective cell growth inhibition by inducing MCF-7 cancer cells to undergo G2/M(cell cycle) phase arrest and apoptosis by an up-regulation of p53 (tumor antigen) expression(68). Unfortunately, epidemiological data,  on incidence of breast cancer and recurrence of breast cancer, consumption of 5 or more cups of green tea a day showed a non-statistically significant trend towards the prevention of breast cancer development. Evidence indicates that green tea consumption may possibly help prevent breast cancer recurrence in early stage (I and II) cancers(69).

3. Red wine
Red wine, made from the pigments of grape varieties is a wine involved extraction of color, and flavour components from the grape skin.
Red wine phenolics piceatannol and myricetin showed to inhibit the profileration of estrogens hormone-dependent breast cancer cells by binding to the gene expression of estrogen receptor (ER) alpha, which interacts with responsive DNA sequences located within the promoter region of target genes(70). Catechin hydrate (CH), an antioxidant in red wine, induced apotoposis against MCF-7 cells, with the rate of 40.7% and 41.16% in the volume of 150 μg/ml CH in 24 hours, respectively. Moreover, a 48-hour exposure to 150 μg/ml CH and 300 μg/ml CH resulted in 43.73% and 52.95% apoptotic cells, through its ability to increase the expression of pro-apoptotic genes such as caspase-3, -8, and -9 and TP53(71).

4. Black bean
Black bean is a Small roughly ovoid legumes with glossy black shells, genus Phaseolus, belonging to the family Fabaceae and can bought in most grocery stores all around the year in dried and canned forms. It is believed that black bean was first domesticated growth in South America.
Water-soluble condensed tannins isolated from black beans showed inhibition against breast cancer cell line MCF-7 at 24 microM by suppressed fetal bovine serum (blood fraction remaining after the natural coagulation of blood) stimulated cell migration and the secretion of matrix metalloproteinase-2 (MMP-2 or gelatinase A), matrix metalloproteinase-9 (MMP-9 or gelatinase B)(involved in the breakdown of extracellular matrix), and vascular endothelial growth factor VEGF(165)(regulator of angiogenesis) receptors expression(72). Phytochemical of black bean (Phaseolus vulgaris) seed coats, also enhanced potent antioxidant and antiproliferative activities against MCF-7 human breast cancer cells in doses depending manner(73).

5. Fermented soybean
Fermented soybean made from ground soybeans, is an popular ingredient used in cuisines of East and Southeast Asia.
Chungkookjang, a Korean fermented soybean, containing high concentration of isoflavones and peptides showed to inhibit the growth of breast cancer MCF7 cells in decreased dependent on the concentration by activating TGFβ pathway in cellular processes and depressing inflammation(74).
In murine breast adenocarcinoma,  fermented soy product (FSP) showed an effectiveness in tumor containment with smallest tumor volumes. Expressed larger amounts of nitric oxide and IL-1β (regulation of immune and inflammatory responses) and exhibited larger tumor sizes(75).

6. Peanut
Peanuts is belong to the the legume related to the bean family and first cultivated in the in the Chaco region of Paraguay and Bolivia.
Lectin ( (PNA), a chemical constituent of peanut was effective in inhibiting proliferation of human breast cell lines (ZR-75.1 and 734-B)(76) and MCF-7, T 47D, HBL 100, BT 20(77). Beta-Sitosterol found in  legumes, oil seeds and unrefined plant oils such as peanut butter, pistachios and sunflower, showed to exhibit the extrinsic apoptotic programmed cell death pathway in human breast MCF-7 and MDA-MB-231(78).

7. Faxseed
Flax seed is native to the region of the eastern Mediterranean to India and also known as common flax or linseed. Flax, an erect annual plant, can grow to 1.2 m tall. The leaves are 20–40 mm long and 3 mm broad.
Study of athymic mice fed with basal diet (control), or 10% FS diet, with or without TRAS (2.5mg/kg) treatment for 5 wk, showed a positive effects in reduced tumor size and increased tumor apoptosis. Dietary FS improved the function of TRAS in increased overall survival(79). In dietary flaxseed lignan or oil combined with tamoxifen showed an enhancing effect in reducing growth of estrogen receptor positive breast tumors (MCF-7) at low circulating estrogen levels by inhibiting cell proliferation, expression of genes, and proteins involved in the ER- and growth factor-mediated signaling pathways(80), with FO greatest effect in increasing apoptosis compared with TAM treatment alone(80). Lignans (a class of phytoestrogens) consumption was associated with a significant reduction in breast cancer risk(81). In estrogen-receptor-positive (MCF-7) and estrogen-receptor-negative (MDA-MB-231) cells, Flaxseed sprouts induced apoptosis and inhibited cancer cell growth by significantly upregulated p53(Anti tumor antigen) mRNA (transmits genetic information from DNA to the cytoplasm and controls certain chemical processes in the cell) in both cell cancer lines(82).

Many hours have been spent, hundred studies have been read, they may be worthless, if this article can not induce some women to change their diet patterns toward plenty vegetables and fruits accompanied with healthy style of living. Vegetables and fruits in the article, indeed, showed a positive effect in inhibiting proliferation  and causing apoptosis in many breast cancer cell lines. But with expansions of GMOs into almost all food sources in production of large scale, approved by FDA and promoted by elective officials for commercial profits with lack of long term studies, organic farming are sitting in the  defendant corner waiting for the death sentence in the next super gene of GMOs cross-contamination. Will the foods in this article be the same in the future? Will they still exert their anti breast cancer effects?.....


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