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Wednesday, February 5, 2014

Breast Cancer in Herbal Medicine Perspective

 Posted by Chantel Martiromo,  Researched Article By Kyle J. Norton

Epidemiological studies. linking herbal medicine in reduced risk of  breast cancer have produced inconstant results. It may be caused by agendas of the originated sources, length of time or following guide lines loosely. Breast cancer widespread in women in Southeast Asian as a result of over 2 decades of economic prosperity has caused major concerns in the governments and scientific communities. Emerged suggestions in searching effective treatments in herbal medicine are ongoing, but discover an effective prevention and treatment with little or no side effects has proven difficult. According to statistic, one in 8 women will be diagnosed to carry some breast cancer tissues sometimes in their life time. Detections of tumor genesis 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 as well as insurance protection in Western world, needless to say of counties which have little.
Breast cancer (malignant breast neoplasm) is a cancer that starts in the tissues of the breast either from the inner lining of milk ducts (Ductal carcinoma) or the lobules (Lobular carcinoma) that supply the ducts with milk. there is also rare cases that breast cancer starts in other areas of the breast.

1. Anise
Anise is a flowering plant of the species of Pimpinella anisum, genus Pimpinella, belonging to the family Apiaceae native to to Egypt and the Mediterranean region. The popular herb has been used in traditional herbal medicine as fragrance in soaps, oils, and mouth fresheners and stomachic, anti-septic, anti-spasmodic, carminative, digestive, expectorant, stimulant and tonic agent  and to treat head-lice, mites, increase blood pressure, prevent formation of gas in the gastrointestinal tract and menstrual cramps, etc.
Anethole, a major chemical compound in Anise, in MTT and colony formation assays, showed to exhibit anti ER+ and ER breast cancer through suppression of cell survival to cell proliferation and induction of apoptosis in MCF-7 and MDA-MB-231 at an optimal concentration of 1 × 10(-3)M by activating immune response in tumor inhibition(1). Epoxypseudoisoeugenol-2-methyl butyrate isolated from Pimpinella corymbosa, inhibited the proliferation of both MCF-7 and BT-549 cells by blocking NF-kappaB(in inflammation, immunity, cell proliferation and apoptosis) transcriptional activity through induced cell cycle arrest in G(1)/G(0)(Cell cycle) phase and apoptosis(2). Also in the study of selective estrogen receptor modulators or SERMs, Pimpinella anisum in a series of in vitro,  exhibited antiestrogenic effect on breast cancer cells of MCF-7(3).

2. Burdock
Burdock is plant in the group of biennial thistles, genus Arctium, belonging to the family Asteraceae, native to the Euro. It has been used over thousand of years in China and other traditional herbal medicine as a diuretic, diaphoretic, and a blood purifying agent and to treat wounds and infections stomach ulcers and other digestive problems.
 Lignin, a chemical constituent in burdock inhibited MDA-MB-231 cell growth by inducing apoptosis through the cell cycle and cell proliferation (ROS/p38 MAPK) pathway and up regulation of (regulator proteins that regulate cell death) Bcl-2 by enhancing antibody antigens(4). Also, in Arctiin in Burdock inhibited the growth of breast caner cells through down-regulation of  cell cycle progression cyclin D1 protein expression(5). Actiin metabolites found in Burdock in the study by the Fourth Military Medical University, in China, showed an inhibited activity on estradiol-mediated proliferation of MCF-7 cells at a concentration of 10 microM(6).

3. Cascara sagrada
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..
Emodin, a chemical compound in Cascara sagrada, showed to reverse the multi-drug resistance in MCF-7/Adr cells and down-regulate ERCC1(the repair of DNA) protein expression(7) and suppress  the proliferation of BCap-37 cells, through the decreased Bcl-2 level(regulate cell death), or induced apoptosis of breast cancer cells by increased expression Bax(involved in p53-mediated apoptosis) and cytosolic(liquid found inside cells) cytochrome c(Protein in the inner membrane of mitochondrial)), on a concentration-and time-dependent manner(8), or through disruption (Bad translocation) of the mitochondrial signaling pathway in BCap-37 cells(9).

4. Turmeric
Turmeric is a perennial plant in the genus Curcuma, belonging to the family Zingiberaceae, native to tropical South Asia. The herb has been used in traditional medicine as anti-oxidant, hypoglycemic, colorant, antiseptic, wound healing agent, and to treat flatulence, bloating, and appetite loss, ulcers, eczema, inflammations, etc.
Curcumin a common spice and the well-known chemopreventive agent in Turmeric, inhibited the level of telomerase gene expression(produces vulnerability of cancer cells) in breast cells treated(10).  Its synthetic version, an ortho-hydroxy substituted analog of curcumin (BDMC-A) inhibited MCF-7 at a dose equivalent to that of curcumin (30μM) on the modulation of selective anti tumorenegtic markers (intrinsic pathway: p53, Bcl-2, Bax, cyt c, Apaf-1, caspase-9, 3, PARP; extrinsic pathway: FasL, caspase 8) and ROS (reactive oxygen species) mediation(11). In MDA-MB-231 and BT-483 breast cancer cells, curcumin exhibited the anti-proliferation effect, through lowering the expression of cyclin D1(involved in regulating cell cycle progression) and MMP1 mRNA(involved in the breakdown of extracellular matrix in normal physiological processes and disease processes)(12).

5. Basil
Basil is a species of Ocimum basilicumm, belonging to the family Lamiaceae. It has been used in traditional medicine to treat cold and flu, coughing, calming the stomach, headache, etc..
Hydrophobic and hydrophilic fractions (HB and HL) in Basil, exhibited anti tumor growth by decreased in basement membrane disintegration, angiogenesis and MMP-2 and MMP-9 activities in in multiple stages of cancer progression(13).Aqueous OG leaf extract in other study, inhibited proliferation, migration, anchorage independent growth, 3D growth and morphogenesis(the biological process of breast cancer) and induction of COX-2 protein(overexpression in breast cancer cells results in increased cell motility and invasion) in breast cancer cells(14).

6. 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.
Mushoom G. lucidum extract (GLE) has been used for the promotion of health, longevity and treatment of cancer. Combination of green tea (GTE) enhanced the effect of G. lucidum extract (GLE) in anti breast cancer cells proliferation (anchorage-dependent growth) through  the down-regulation of expression of oncogene c-myc (frequently altered in human cancers) in MDA-MB-231 cells(15). In green tea polyphenols (GTPs), epigallocatechin-3-gallate (EGCG) induced apoptosis, cell cycle arrest and suppression of metastasis in tumor cells(16). Unfortunately, in the study of Green tea consumption and breast caner risk in Japanese women, showed that a green tea consumption is not associated with a decreased risk of breast cancer(17).

7. Red clover
Red Clover is a short-lived perennial plant, in the genus Trifolium, belonging to the family Fabaceae, native to to Europe, Western Asia and northwest Africa. The herb has been used in traditional medicine as diuretic and liver cleansing agent and to treat cancer, whooping cough, respiratory problems, and skin inflammations, etc.
Formononetin, a major compound in Red clover, inactivated IGF1/IGF1R-PI3K/Akt (tumorenegtic) pathways and decreased cyclin D1 mRNA(regulating cell cycle progression) and protein expression in human breast cancer cells in vitro and in vivo(18) and through Ras inhibited p38MAPK pathway(19). Unfortunately, in the study of  Soy, red clover, and isoflavones and breast cancer, suggest that red clover may not possess breast cancer-promoting effects(20).

8. Black cohosh
Black cohosh (known as both Actaea racemosa and Cimicifuga racemosa), a member of is a perennial plant, belonging to the family buttercup, native to North America. The herb has been used in herbal medicine to treat symptoms of menopause, premenstrual syndrome (PMS), painful menstruation, acne, osteoporosis, and for starting labor in pregnant women.
Triterpene glycoside actein from black cohoch showed to inhibit the growth of human breast cancer cells and induced a dose dependent release of calcium into the cytoplasm(fluid protoplasm) by altering the activity of the ER IP3(messenger) receptor and Na,K-ATPase(enzyme pumps sodium out of cells)(21). In Female Sprague-Dawley rats treated with an extract of black cohosh enriched in triterpene glycosides (27%), showed an inhibition of fibroadenomas by reduced Ki-67 and cyclin D1 protein expression.(22).

9. Echinacea
Enchinanea also known as purple coneflowers, is a flowering plant of the genus Enchinanea, belonging to the family Asteraceae, native to eastern and central North America. The herb has been used in traditional and herbal medicine to treat or prevent colds, flu, infections by stimulating the immune function, etc..
Cynarine, a chemical compound in Enchinanen affected cell proliferation on HeLa cells and antiproliferative activity on MCF-7 cells(23).

10. Parsley
Parsley (Petroselinum crispum) is a biennial flowering plant, genus Petroselinum, belonging to the family Apiaceae, native to the Mediterranean region of southern Europe. The herb has been used in traditional medicine as diuretic agent, and to release spasms, reduce inflammation, clear toxins, enhance the digestion and stimulate uterus, regulate menstrual cycle, treat edema, etc..
Parley alcoholic seed extract (PSA) and seed oil (PSO) of Petroselinum sativum significantly reduced cell viability, and altered the cellular morphology of MCF-7 cells in a concentration dependent manner(24). Carnosol found in parsley, and others herbs such as rosemary, sage, targeted multiple deregulated pathways associated with inflammation and cancer(25). 

11. Rosemary
Rosemary is a perennial herb with fragrant, evergreen, needle-like leaves, the genus Rosmarinus, belonging to the family Lamiaceae. Its fresh and dried leaves has been used frequently in traditional Mediterranean cuisine and as flavor foods while barbecuing. Rosemary has been used in traditional medicine as an antiseptic, antioxidant, and antispasmodic agent to treat circulatory problem, eczema, rheumatism, muscle pain, etc.
Carnosic acid isolated from Rosemary, showed to inhibit proliferation of ER-negative human breast cancer cells and induces G1 cell cycle arrest(26). Other in the study of rosemary extract, carnosol, carnosic acid, ursolic acid, and rosmarinic acid suppressed the development of tumors in several organs including breasts(27). In MDA-MB-231, Rosmarinus officinalis had superior antiproliferative effect without induced toxicity(28).

12. Peppermint
Peppermint is a hybrid mint with small purple or white flowers and downy leaves, in the genus Mentha, belonging to the family Lamiaceae, native to to Europe. The herb has been used in folk medicine as analgesic, antiseptic, antispasmodic, decongestant, agent and to relieve gas, nausea, and stomach pain due to an irritable bowel, intestinal cramps, or indigestion, infecttion, etc.
Dried aqueous extractsform Mentha piperita (ExMp) showed cytotoxicity, against MCF-7 with the least toxicity(29).

13. Thyme
Thyme is a  genus of Thymus, belonging to the family Lamiaceae, native to Europe and North Africa. The herb has been used in flok nedicine to treat  bronchitis, whooping cough, sore throat, colic, arthritis, upset stomach, stomach pain (gastritis), diarrhea, bedwetting, etc..
Thyme extract exhibited significant cytotoxicity and apoptosis in breast cancer cells (MCF-7 and MDA-MB-231)(30)(31). In the study in comparison of some herbs for their effects in human prostate carcinoma cell (PC-3), human lung carcinoma (A549) and human breast cancer (MCF-7) cell lines, thyme essential oil exhibited the strongest cytotoxicity towards the above three human cancer cells(32).

14. Garlic
Garlic (Allium sativum) is a species in the onion genus, belonging to family Amaryllidaceae, native to central Asia. It has been used popularly in traditional and Chinese medicine in treating common cold and flu to the Plague, blood pressure cholesterol levels, natural antibiotic, etc..
In a case-control study of 345 patients with dietary history questionnaire consisted of a self-administered food frequency questionnaire, showed breast cancer risk was shown to decrease as increased consumption of  garlic and onions(33). In breast cancer cells MCF-7 and MCF-7(ras), aged garlic extract (AGE) and two of its components, S-allylcysteine (SAC), and S-allyl-mercaptocysteine (SAMC) showed anti-proliferative response due to the alteration in glutathione(antioxidants) level without significant concurrent changes in the glutathione metabolizing enzymes(34). In a breast-cancer cell line (MCF-7), Diallyl disulphide (DADS), a chemical component in garlic, induced phosphatidylserine translocation from the inner to the outer leaflet of the plasma membrane and activates caspase(mechanisms of apoptosis)-3. DADS also modulated the cellular levels of Bax, Bcl-2, Bcl-xL, and Bcl-w (induced apoptosis), in a dose-dependent manner(35).

15. Ginkgo biloba
Ginkgo biloba is oldest living tree species, genus Ginkgo, belonging to the family Ginkgoaceae, native to China, from temperate zone to subtropical zone and some parts of north America. It Has been used in traditional herbal medicine in treating impotence, memory loss, respiratory diseases, circulatory disorders and deafness as well as preventing drunkenness, and bedwetting.
Ginkgo biloba extract (GbE) used conjunction with Tamoxifen (TAM) in female Sprague-Dawley (SD) rats, showed a slightly beneficial effect on the therapeutic efficacy of TAM in female SD breast cancer bearing rats(36). In the experiment of Ginkgo biloba extract (GBE) effected against MDA-MB-231 (ER-negative) human breast cancer cell line, showed that cytotoxicity effects of GBE in MDA-MB-231 lead to DNA fragmentation at high concentrations (500 and 1,000 μg/ml). activated the Caspase-3 and mRNA levels of apoptosis-related genes (Bcl-2 and Bax)(37). In the study of Antiestrogenic activities of extract of Ginkgo biloba, showed an reduced E2 levels by stimulating the E2 metabolism and inhibiting E2 synthesis.(38).

16. Reishi Mushroom
Reishi mushroom or Lingzhi is a fungal species in the genus Ganoderma, belonging to the family Ganodermataceae, native to Asia. The herb has been use in traditional medicine as anti-caners and anti inflammatory, antioxidant agent and to enhance immune function, treat hepatitis B virus, protect against neuron degeneration, etc..
In Inflammatory Breast Cancer (IBC), with overexpress E-cadherin (plays an important role in the growth, development and the intercellular adhesion of epithelial cells) and the eukaryotic initiation factor 4GI (eIF4GI)(an essential protein that is the target for translational regulation in many cellular processes), Reishi  showed reduced expression of E-cadherin, mTOR(cell proliferation), eIF4G, and p70S6K(cell growth and G1 cell cycle progression) and cell regulation activities(activity of extracellular regulated kinase (ERK1/2))(39). In the study of the same, Reishi showed to inhibited the expression of genes involved in cancer cell survival and proliferation (BCL-2, TERT, PDGFB) of  invasion and metastasis breast cancer cells(MMP-9)(40). An ethanol-soluble and acidic component (ESAC) prepared from Reishi reduced the cell viability of MCF-7 and MDA-MB-231 cells in a concentration-dependent manner with IC(50) of about 100 μg/mL and 60 μg/mL, respectively through effectively mediated G1 cell cycle arrest and exhibited apoptosis(41).

17. Grape Seed Extract
Grape Seed Extract is the commercial extracts from whole grape seeds that contains many concentrations, including vitamin E, flavonoids, linoleic acid, oligomeric proanthocyanidins(OPCs), etc..The herb has been used in traditional medicine as antioxidant, anti-inflammatory agents and to treat skin wounds with less scarring, allergies, macular degeneration, arthritis, enhance circulation of blood vessels, lower cholesterol, etc.
In highly metastatic MDA-MB231 breast cancer cell line, grape seed extract (GSE)showed the effectiveness in cell proliferation and apoptosis through decreased cell migration and invasion, likely by suppressing the β-catenin((plays an important role in the growth, development and the intercellular adhesion of epithelial cells) expression and localization, fascin(cell motility and migration) and NF-κB((a transcription factor that has crucial roles in inflammation, immunity, cell proliferation and apoptosis) expression(42). Proanthocyanidin, other chemical constituent in grape seeds, showed to suppress  precancerous cellular carcinogenesis through down regulated gene expression of cytochrome-P450 enzymes CYP1A1 and CYP1B1(carcinogenic intermediates)(43). In breast cancer cell MCF-7, Grape seed extract inhibited the proliferation and downregulated the gene expression of survivin(baculoviral inhibitor)through through arresting the cell cycle in S phase((synthesis phase for DNA reduplication))(44)

18. Dandelion
Dandelion is a herbaceous perennial plant, genus Taraxacum, beloning to the family Asteraceae, native to temperate regions of the world. It has been used in traditional and herbal medicine to treat gout, eczema, acne, gall bladder, kidney, liver and urinary disorders, hypoglycemia, dyspepsia with constipation, edema, blood pressure and heart weakness, chronic joint, skin diseases, etc.
Aqueous extracts  extracts (DRE), from the mature leaves, flowers and roots of dandelion were investigated for the effects in tumor progression in related processes such as proliferation and invasion, only the crude extract of dandelion leaf (DLE) showed to decrease the growth of MCF-7/AZ breast cancer cells in an ERK(transmits signals from many extracellular agents to regulate cellular processes such as proliferation, differentiation and cell cycle progression)(45)-dependent manner(46).

19. Ginseng
Ginseng is a slow-growing perennial plants with fleshy roots, the genus Panax, belonging to the family Araliaceae. Depending to the climate where it grows, ginseng can be classified mainly into Panax ginseng Asian ginseng (root), Red ginseng, wild ginseng, American ginseng (root).
The investigation of Ginseng effects in a cohort of 1,455 breast cancer patients recruited to the Shanghai Breast Cancer Study between August 1996 and March 1998 in Shanghai, China showed that Ginseng use after cancer diagnosis, particularly current use, improved quality of life and reduced risk of death(47). In breast cancer cell line MCF-7 cells, Korean red ginseng (KRG) extracts activated the ERα and ERβ (Estrogen receptor alpha and Beta) through regulating the mRNA levels of estrogen-responsive genes such as pS2 and ESR1 to decreased the protein level of ERα. Also Ginsenoside from Panax notoginseng decreased the survival of breast cancer cells by induction of apoptosis and G1(cell cycle) phase arrest and inhibited the growth of breast cancer xenografts(a graft obtained from breast cancer cells of one species and transplanted to a member of another species) in vivo(49) and inhibited MDM2(an oncoprotein that controls tumorigenesis) expression at both transcriptional(gene expression at the RNA) and post-translational levels in human breast cancer cells with various p53(cellular tumor antigen) statuses(49).

20. Hawthorn
Hawthorn is a shrubs and trees of the genus Crataegus, belonging to the family Rosaceae, native to temperate regions of the Northern Hemisphere in Europe, Asia and North America. The herb has been used in traditional medicine to treat heart disease and symptoms of heart diseases such as irregular heartbeat, high blood pressure, chest pain, hardening of the arteries, etc., circulatory disorders and respiratory illnesses.
In in human MCF-7 breast carcinoma cells, peel polyphenolic extract (HPP) and flesh polyphenolic extract (HFP) from hawthorn fruit although HPP was more effective against MCF-7 cells than HFP, both HPP and HFP interfereed the cell-cycle arrest at the S-phase, and also dose-dependently led to apoptosis of MCF-7 cells via the mitochondrial pathway(inner mitochondrial membrane), by the mechanism of apoptosis of caspase-3 and caspase-9  and the elevation of intracellular ROS(reactive oxygen species) production(50).

21. Licorice (Glycyrrhiza Glabra)
Licorice (Glycyrrhiza Glabra) is also known as sweetwood, a genus Glycyrrhiza, belonging to the family Fabaceae, native to the Mediterranean and certain areas of Asia. The herb has been used in traditional medicine to treat skin diseases, coughs, constipation, bronchitis, inflammation, arthritis, etc..
Isoliquiritigenin, a flavonoid phytoestrogen from licorice, induced growth inhibition and apoptosis through downregulating multiple key enzymes in AA metabolic network(inflammatory mediators) and the deactivation of anti-apoptosis and increased cell proliferation(PI3K/Akt)  in human breast cancer(51). Licochalcone E (LicE), other phenolic constituent of licorice, in MDA-MB-231 cells inhibited cell migration and invasion and downregulated the expression of proliferative and anti apoptotic pathways and unregulated secretion of cell proliferation inhibitor(52). Ethanol extract of roasted licorice (rLE) found to be effective in inhibition of breast cancer-mediated bone destruction  by suppressing receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast formation in BMMs(bone marrow-derived macrophages (BMMs)(53).

22, Oregano
Oregano is a perennial herb with aromatic and balsamic flavor, of the genus Origanum in the family Lamiaceae, native to western and southwestern Eurasia and the Mediterranean. The herb has been used in traditional medicine as anti-bacterial, anti-fungal, and anti-viral agent and to treat skin burns, cuts and bruises, sore throat, asthma, colds, coughs and flu, etc.
Carvacrol, a chemical constituent in Oregano showed the anti-tumor effects on human metastatic breast cancer cells, MDA-MB 231 through down regulated the function of mitochondrial membrane potential of the cells(54). In breast cancer cell lines MCF-7, MDA-MB-468 and MDA-MB-231, Origanum acutidens (OA) extracts showed cytotoxicity on all 3 cancer cell lines through expression of Annexin-positive cells level in OA-treated cell lines and caspase-7 (transduction pathways of apoptosis, necrosis and inflammation) protein and TUNEL-positive (indication of apoptosis and accidental cell death) cells(55). In the investigation of essential oil from oregano leaves (Origanum compactum), showed that ethyl acetate extract (30 mg/L) and ethanol extract (56 mg/L) are effective in ambition against human breast cancer cells (MCF7)(56).

23. Rhubarb
Rhubarb is a small flower grouped with large compound leafy in the the genus Rheum, belonging to the family Polygonaceae. The herb has been used in traditional medicine as laxative agent, reduce inflammation and treat diarrhea, dysentery blood clots, tumor red and painful eyes abdominal-distention and/or pain blood in stool hemorrhoidal bleeding urination: burning sensation, absence of menses, etc.
Anthraquinones emodin and aloe-emodin chemical constituents in rhubarb, both inhibited breast cancer cell proliferation by downregulating ER α protein levels in suppressing ER α transcriptional activation(57). Study of combined curcumin and emodin administration showed the inhibition of proliferation (MTT assay), survival (flow cytometry), and invasion (transwell migration assay) of breast cancer cells(58). Rhein, a anthraquinone derivatives, showed antiproliferative and apoptotic effects on both HER2-overexpressing MCF-7 (MCF-7/HER2) and control vector MCF-7 (MCF-7/VEC) cells(59).

24. Cat's claw
Cat's claw found in in the tropical jungles of South and Central America, is a genus Uncaria, belonging to the family Rubiaceae. It has been used in traditional medicine over two thousand years as a tonic, contraceptive, anti-inflammatory and infectious agent, and to treat diarrhea, rheumatic disorders, acne, diabetes, cancer and diseases of the urinary tract, etc..
Extracts and chromatographic fractions of the Cat's claw, exerted a direct antiproliferative activity on MCF7, with an IC50 of 10 mg/ml and 20 mg/ml, respectively.60). Also, pentacyclic oxindole alkaloid mitraphylline isolated from Uncaria tomentosa bark, using cyclophosphamide and vincristine as reference controls, showed to inhibit the growth of both human sarcoma and breast cancer cell lines in a dose-dependent manner(60).

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References
(1) Anethole suppressed cell survival and induced apoptosis in human breast cancer cells independent of estrogen receptor status by Chen CH, deGraffenried LA.(PubMed)
(2) Inhibition of NF-kappaB-mediated transcription and induction of apoptosis in human breast cancer cells by epoxypseudoisoeugenol-2-methyl butyrate by Ma G, Tabanca N, Husnu Can Baser K, Kirimer N, Pasco DS, Khan IA, Khan SI.(PubMed)
(3) Greek plant extracts exhibit selective estrogen receptor modulator (SERM)-like properties by Kassi E, Papoutsi Z, Fokialakis N, Messari I, Mitakou S, Moutsatsou P.(PubMed)
(4) Arctigenin, a dietary phytoestrogen, induces apoptosis of estrogen receptor-negative breast cancer cells through the ROS/p38 MAPK pathway and epigenetic regulation by Hsieh CJ1, Kuo PL2, Hsu YC3, Huang YF4, Tsai EM5, Hsu YL6.(PubMed)
(5) ROS-activated p38 MAPK/ERK-Akt cascade plays a central role in palmitic acid-stimulated hepatocyte proliferation by  Matsuzaki Y, Koyama M, Hitomi T, Yokota T, Kawanaka M, Nishikawa A, Germain D, Sakai T.(PubMed)
(6) ROS-activated p38 MAPK/ERK-Akt cascade plays a central role in palmitic acid-stimulated hepatocyte proliferation by  Xie LH, Ahn EM, Akao T, Abdel-Hafez AA, Nakamura N, Hattori M.(PubMed)
(7) Emodin affects ERCC1 expression in breast cancer cells by Fu JM, Zhou J, Shi J, Xie JS, Huang L, Yip AY, Loo WT, Chow LW, Ng EL.(PubMed)
(8) Emodin-induced apoptosis in human breast cancer BCap-37 cells through the mitochondrial signaling pathway by Huang Z, Chen G, Shi P.(PubMed)
(9) Effects of emodin on the gene expression profiling of human breast carcinoma cells by Huang Z, Chen G, Shi P.(PubMed)
(10) Comparison of inhibitory effect of curcumin nanoparticles and free curcumin in human telomerase reverse transcriptase gene expression in breast cancer by Kazemi-Lomedasht F, Rami A, Zarghami N.(PubMed)
(11) Mechanism of apoptotic induction in human breast cancer cell, MCF-7, by an analog of curcumin in comparison with curcumin - An in vitro and in silico approach by Mohankumar K1, Pajaniradje S1, Sridharan S1, Singh VK2, Ronsard L3, Banerjea AC3, Benson CS4, Coumar MS2, Rajagopalan R(PubMed)
(12) Curcumin inhibits cell proliferation of MDA-MB-231 and BT-483 breast cancer cells mediated by down-regulation of NFkappaB, cyclinD and MMP-1 transcription by Liu Q, Loo WT, Sze SC, Tong Y.(PubMed)
(13) Ocimum gratissimum retards breast cancer growth and progression and is a natural inhibitor of matrix metalloproteases by Nangia-Makker P, Raz T, Tait L, Shekhar MP, Li H, Balan V, Makker H, Fridman R, Maddipati K, Raz A.(PubMed)
(14) Inhibition of breast tumor growth and angiogenesis by a medicinal herb: Ocimum gratissimum by Nangia-Makker P, Tait L, Shekhar MP, Palomino E, Hogan V, Piechocki MP, Funasaka T, Raz A(PubMed)
(15) Combined effect of green tea and Ganoderma lucidum on invasive behavior of breast cancer cells by Thyagarajan A, Zhu J, Sliva D.(PubMed)
(16)Downstream Carcinogenesis Signaling Pathways by Green Tea Polyphenols: A Translational Perspective of Chemoprevention and Treatment for Cancers by Hu G, Zhang L, Rong Y, Ni X, Sun Y.(PubMed)
(17) Green tea consumption and breast cancer risk in Japanese women: a case-control study by Iwasaki M, Mizusawa J, Kasuga Y, Yokoyama S, Onuma H, Nishimura H, Kusama R, Tsugane S.(PubMed)
(18) Formononetin induces cell cycle arrest of human breast cancer cells via IGF1/PI3K/Akt pathways in vitro and in vivo by Chen J, Zeng J, Xin M, Huang W, Chen X.(PubMed)
(19)Formononetin-induced apoptosis by activation of Ras/p38 mitogen-activated protein kinase in estrogen receptor-positive human breast cancer cells by Chen J, Sun L.(PubMed)
(20) Soy, red clover, and isoflavones and breast cancer: a systematic review by Fritz H, Seely D, Flower G, Skidmore B, Fernandes R, Vadeboncoeur S, Kennedy D, Cooley K, Wong R, Sagar S, Sabri E, Fergusson D.(PubMed)
(21) Actein induces calcium release in human breast cancer cells by Einbond LS, Mighty J, Redenti S, Wu HA.(PubMed)
(22) Chemopreventive potential of black cohosh on breast cancer in Sprague-Dawley rats by Einbond LS, Soffritti M, Degli Esposti D, Tibaldi E, Lauriola M, Bua L, He K, Genovese G, Su T, Huggins L, Wang X, Roller M, Wu HA.(PubMed)
(23) Proliferative activity of Echinacea angustifolia root extracts on cancer cells: Interference with doxorubicin cytotoxicity by Huntimer ED, Halaweish FT, Chase CC.(PubMed)
(24) Anticancer activity of Petroselinum sativum seed extracts on MCF-7 human breast cancer cells by Farshori NN, Al-Sheddi ES, Al-Oqail MM, Musarrat J, Al-Khedhairy AA, Siddiqui MA.(PubMed)
(25) Carnosol: a promising anti-cancer and anti-inflammatory agent by Johnson JJ.(PubMed)
(26) Carnosic acid inhibits the growth of ER-negative human breast cancer cells and synergizes with curcumin by Einbond LS, Wu HA, Kashiwazaki R, He K, Roller M, Su T, Wang X, Goldsberry S.(PubMed)
(27) Rosemary and cancer prevention: preclinical perspectives by Ngo SN, Williams DB, Head RJ.(PubMed)
(28) Inhibitory effects of rosemary extracts, carnosic acid and rosmarinic acid on the growth of various human cancer cell lines by Yesil-Celiktas O, Sevimli C, Bedir E, Vardar-Sukan F.(PubMed)
(29) Cytotoxic impact of phenolics from Lamiaceae species on human breast cancer cells by Berdowska I, Zieliński B, Fecka I, Kulbacka J, Saczko J, Gamian A.(PubMed)
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1 comment:

  1. I am following just in order to present this layman's theory on breast cancer. I also had a good friend who died at age 43 from cervical cancer. Perhaps my idea will work for both. I myself am a survivor of prostate cancer. THE IDEA: If you catch a house fire early enough, before the smoke detector can sense it, you can put it out with a squirt gun instead of a fire hose, and with much less damage (invasive surgery). So, at the statistical age when many women develop a lump, or a few years sooner (I am guessing age 40), take a sampling of women volunteers and give them a low dose of chemotherapy, possibly diluted with saline so it can be injected into a simple IV instead of via a catheter into the heart. The dose and duration should be such that only a few strands of hair are lost, if any. I imagine the patient would feel some nausea or other discomfort similar to a bout with the flu. Next, monitor the test group for 40 years to see if there is a reduction in the % who contract a lump. At age 80, if the process proves successful, I would repeat it because both my mother and aunt had lumps in the same spot at nearly the same time, though my aunt is a few years younger. Thank you and my degree is in engineering, not medicine.

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