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Zhu L, Hshieh TT, Iyer TK, Morgans AK, Hamnvik OPR. Management of vasomotor symptoms in cancer patients. Oncologist 2025; 30:oyaf002. [PMID: 40037618 PMCID: PMC11879400 DOI: 10.1093/oncolo/oyaf002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Accepted: 11/11/2024] [Indexed: 03/06/2025] Open
Abstract
Many cancer treatments can lead to reduced levels of sex hormones, which in turn may cause vasomotor symptoms (VMS) such as hot flashes. These symptoms are associated with impaired quality of life, as well as suboptimal tolerability of and adherence to cancer treatment. Hormone therapy, performed by increasing estradiol or testosterone levels, is the gold standard for treatment of VMS. However, this approach is generally contraindicated in patients with hormone-sensitive cancers. Nonhormone agents with low to moderate efficacy in controlling VMS are available, but their use may be limited by side effects and tolerability. In this narrative review, the approach to VMS in cancer patients will be discussed. The evidence for various treatment options, including novel agents such as fezolinetant that target the hypothalamic thermoregulatory pathway, will be evaluated. Finally, special considerations in different patient populations based on cancer types (eg, breast, prostate) and age groups (eg, older adults) will be explored.
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Affiliation(s)
- Ling Zhu
- Department of Endocrinology, Singapore General Hospital, Singapore 169856
- Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States
| | - Tammy T Hshieh
- Division of Aging, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States
| | - Tara K Iyer
- Menopause and Midlife Clinic, Division of Women’s Health, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02215, United States
| | - Alicia K Morgans
- Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, United States
| | - Ole-Petter R Hamnvik
- Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States
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Shea Z, Ogando do Granja M, Fletcher EB, Zheng Y, Bewick P, Wang Z, Singer WM, Zhang B. A Review of Bioactive Compound Effects from Primary Legume Protein Sources in Human and Animal Health. Curr Issues Mol Biol 2024; 46:4203-4233. [PMID: 38785525 PMCID: PMC11120442 DOI: 10.3390/cimb46050257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 04/22/2024] [Accepted: 04/30/2024] [Indexed: 05/25/2024] Open
Abstract
The global demand for sustainable and nutritious food sources has catalyzed interest in legumes, known for their rich repertoire of health-promoting compounds. This review delves into the diverse array of bioactive peptides, protein subunits, isoflavones, antinutritional factors, and saponins found in the primary legume protein sources-soybeans, peas, chickpeas, and mung beans. The current state of research on these compounds is critically evaluated, with an emphasis on the potential health benefits, ranging from antioxidant and anticancer properties to the management of chronic diseases such as diabetes and hypertension. The extensively studied soybean is highlighted and the relatively unexplored potential of other legumes is also included, pointing to a significant, underutilized resource for developing health-enhancing foods. The review advocates for future interdisciplinary research to further unravel the mechanisms of action of these bioactive compounds and to explore their synergistic effects. The ultimate goal is to leverage the full spectrum of benefits offered by legumes, not only to advance human health but also to contribute to the sustainability of food systems. By providing a comprehensive overview of the nutraceutical potential of legumes, this manuscript sets a foundation for future investigations aimed at optimizing the use of legumes in the global pursuit of health and nutritional security.
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Affiliation(s)
- Zachary Shea
- United States Department of Agriculture–Agricultural Research Service, Raleigh Agricultural Research Station, Raleigh, NC 27606, USA;
| | - Matheus Ogando do Granja
- School of Plant and Environmental Sciences, Virginia Tech, Blacksburg, VA 24061, USA; (M.O.d.G.); (E.B.F.); (Y.Z.); (P.B.); (Z.W.)
| | - Elizabeth B. Fletcher
- School of Plant and Environmental Sciences, Virginia Tech, Blacksburg, VA 24061, USA; (M.O.d.G.); (E.B.F.); (Y.Z.); (P.B.); (Z.W.)
| | - Yaojie Zheng
- School of Plant and Environmental Sciences, Virginia Tech, Blacksburg, VA 24061, USA; (M.O.d.G.); (E.B.F.); (Y.Z.); (P.B.); (Z.W.)
| | - Patrick Bewick
- School of Plant and Environmental Sciences, Virginia Tech, Blacksburg, VA 24061, USA; (M.O.d.G.); (E.B.F.); (Y.Z.); (P.B.); (Z.W.)
| | - Zhibo Wang
- School of Plant and Environmental Sciences, Virginia Tech, Blacksburg, VA 24061, USA; (M.O.d.G.); (E.B.F.); (Y.Z.); (P.B.); (Z.W.)
- Donald Danforth Plant Science Center, Olivette, MO 63132, USA
| | - William M. Singer
- Center for Advanced Innovation in Agriculture, Virginia Tech, Blacksburg, VA 24061, USA;
| | - Bo Zhang
- School of Plant and Environmental Sciences, Virginia Tech, Blacksburg, VA 24061, USA; (M.O.d.G.); (E.B.F.); (Y.Z.); (P.B.); (Z.W.)
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Singh S, Grewal S, Sharma N, Behl T, Gupta S, Anwer MK, Vargas-De-La-Cruz C, Mohan S, Bungau SG, Bumbu A. Unveiling the Pharmacological and Nanotechnological Facets of Daidzein: Present State-of-the-Art and Future Perspectives. Molecules 2023; 28:1765. [PMID: 36838751 PMCID: PMC9958968 DOI: 10.3390/molecules28041765] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 02/02/2023] [Accepted: 02/10/2023] [Indexed: 02/17/2023] Open
Abstract
Herbal drugs have been attracting much scientific interest in the last few decades and nowadays, phytoconstituents-based research is in progress to disclose their unidentified medicinal potential. Daidzein (DAI) is the natural phytoestrogen isoflavone derived primarily from leguminous plants, such as the soybean and mung bean, and its IUPAC name is 4',7-dihydroxyisoflavone. This compound has received great attention as a fascinating pharmacophore with remarkable potential for the therapeutic management of several diseases. Certain pharmacokinetic properties of DAI such as less aqueous solubility, low permeability, and poor bioavailability are major obstacles restricting the therapeutic applications. In this review, distinctive physicochemical characteristics and pharmacokinetics of DAI has been elucidated. The pharmacological applications in treatment of several disorders like oxidative stress, cancer, obesity, cardiovascular, neuroprotective, diabetes, ovariectomy, anxiety, and inflammation with their mechanism of action are explained. Furthermore, this review article comprehensively focuses to provide up-to-date information about nanotechnology-based formulations which have been investigated for DAI in preceding years which includes polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carrier, polymer-lipid nanoparticles, nanocomplexes, polymeric micelles, nanoemulsion, nanosuspension, liposomes, and self-microemulsifying drug delivery systems.
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Affiliation(s)
- Sukhbir Singh
- Department of Pharmaceutics, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to Be University), Ambala 133207, India
| | - Sonam Grewal
- Department of Pharmaceutics, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to Be University), Ambala 133207, India
| | - Neelam Sharma
- Department of Pharmaceutics, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to Be University), Ambala 133207, India
| | - Tapan Behl
- School of Health Sciences & Technology, University of Petroleum and Energy Studies, Bidholi, Dehradun 248007, India
| | - Sumeet Gupta
- Department of Pharmacology, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to Be University), Ambala 133207, India
| | - Md. Khalid Anwer
- Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj 11942, Saudi Arabia
| | - Celia Vargas-De-La-Cruz
- Department of Pharmacology, Bromatology and Toxicology, Faculty of Pharmacy and Biochemistry, Universidad Nacional Mayor de San Marcos, Lima 15081, Peru
- E-Health Research Center, Universidad de Ciencias y Humanidades, Lima 15081, Peru
| | - Syam Mohan
- School of Health Sciences & Technology, University of Petroleum and Energy Studies, Bidholi, Dehradun 248007, India
- Substance Abuse and Toxicology Research Centre, Jazan University, Jazan 45142, Saudi Arabia
- Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Science, Saveetha University, Chennai 602117, India
| | - Simona Gabriela Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania
- Doctoral School of Biomedical Sciences, University of Oradea, 410087 Oradea, Romania
| | - Adrian Bumbu
- Department of Surgery, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
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Batool M, Ranjha MMAN, Roobab U, Manzoor MF, Farooq U, Nadeem HR, Nadeem M, Kanwal R, AbdElgawad H, Al Jaouni SK, Selim S, Ibrahim SA. Nutritional Value, Phytochemical Potential, and Therapeutic Benefits of Pumpkin ( Cucurbita sp.). PLANTS (BASEL, SWITZERLAND) 2022; 11:1394. [PMID: 35684166 PMCID: PMC9182978 DOI: 10.3390/plants11111394] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 05/20/2022] [Accepted: 05/21/2022] [Indexed: 05/05/2023]
Abstract
Pumpkin is a well-known multifunctional ingredient in the diet, full of nutrients, and has opened new vistas for scientists during the past years. The fruit of pumpkin including the flesh, seed, and peel are a rich source of primary and secondary metabolites, including proteins, carbohydrates, monounsaturated fatty acids, polyunsaturated fatty acids, carotenoids, tocopherols, tryptophan, delta-7-sterols, and many other phytochemicals. This climber is traditionally used in many countries, such as Austria, Hungary, Mexico, Slovenia, China, Spain, and several Asian and African countries as a functional food and provides health promising properties. Other benefits of pumpkin, such as improving spermatogenesis, wound healing, antimicrobial, anti-inflammatory, antioxidative, anti-ulcerative properties, and treatment of benign prostatic hyperplasia have also been confirmed by researchers. For better drug delivery, nanoemulsions and niosomes made from pumpkin seeds have also been reported as a health promising tool, but further research is still required in this field. This review mainly focuses on compiling and summarizing the most relevant literature to highlight the nutritional value, phytochemical potential, and therapeutic benefits of pumpkin.
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Affiliation(s)
- Maria Batool
- University Institute of Diet and Nutritional Sciences, University of Lahore, Gujrat 50700, Pakistan;
| | | | - Ume Roobab
- School of Food Science and Engineering, South China University of Technology, Guangzhou 510641, China; (U.R.); (R.K.)
| | | | - Umar Farooq
- Department of Food Science and Technology, Muhammad Nawaz Shareef University of Agriculture, Multan 59300, Pakistan;
| | - Hafiz Rehan Nadeem
- Institute of Food Science and Nutrition, Bahauddin Zakariya University, Multan 59300, Pakistan;
| | - Muhammad Nadeem
- Institute of Food Science and Nutrition, University of Sargodha, Sargodha 40100, Pakistan; (M.M.A.N.R.); (M.N.)
| | - Rabia Kanwal
- School of Food Science and Engineering, South China University of Technology, Guangzhou 510641, China; (U.R.); (R.K.)
| | - Hamada AbdElgawad
- Integrated Molecular Plant Physiology Research, Department of Biology, University of Antwerp, 2020 Antwerpen, Belgium;
- Botany and Microbiology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62511, Egypt
| | - Soad K. Al Jaouni
- Department of Hematology/Oncology, Yousef Abdulatif Jameel Scientific Chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
| | - Samy Selim
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Saudi Arabia
| | - Salam A. Ibrahim
- Food Microbiology and Biotechnology Laboratory, North Carolina Agricultural and Technical State University, Greensboro, NC 27411, USA
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Han D, Chung M, Park Y. Association of Dietary Total Antioxidant Capacity with Cancer Recurrence and Mortality among Breast Cancer Survivors: A Prospective Cohort Study. Nutr Cancer 2022; 74:3253-3262. [PMID: 35535682 DOI: 10.1080/01635581.2022.2074061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Antioxidants decrease the risk of breast cancer by reducing oxidative stress, but the association between dietary total antioxidant capacity (DTAC) and cancer recurrence has not yet been investigated. The present study aimed to test the hypothesis that DTAC is inversely associated with cancer recurrence and mortality in breast cancer patients. Breast cancer patients (n = 603) who underwent breast cancer surgery and a dietary survey within 5 years after surgery were recruited. This study observed disease-free survival (DFS) and mortality in breast cancer patients according to DTAC calculated based on 24-hr dietary recall. Total DTAC was significantly lower in patients with cancer recurrence than in those without. DFS was positively associated with the total DTAC (p = 0.005) and DTAC of vegetables and legumes (p = 0.001 and p = 0.010), respectively. However, total DTAC was not associated with mortality. Cox proportional hazards regression analysis showed that total DTAC (HR: 0.44, 95% CI 0.26-0.94) and DTAC of vegetables (HR: 0.30, 95% CI 0.14-0.65) and legumes (HR: 0.38, 95% CI 0.18-0.73) were inversely associated with cancer recurrence after adjusting for confounding factors. This study was the first to indicate that total DTAC and DTAC of vegetables and legumes could be beneficial in decreasing breast cancer recurrence.
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Affiliation(s)
- Doyeon Han
- Department of Food and Nutrition, Hanyang University, Seoul, Korea
| | - Minsung Chung
- Department of Surgery, Hanyang University Hosipital, Seoul, Korea
| | - Yongsoon Park
- Department of Food and Nutrition, Hanyang University, Seoul, Korea
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Screening of Immune-Related Genes and Predicting the Immunotherapeutic Effects of Formononetin in Breast Cancer: A Bioinformatics Analysis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:9942373. [PMID: 35463082 PMCID: PMC9033346 DOI: 10.1155/2022/9942373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 03/11/2022] [Accepted: 03/18/2022] [Indexed: 12/24/2022]
Abstract
Objective Immunotherapy is a promising breast cancer treatment. Nonetheless, tumor heterogeneity and the interaction between immune cells in the tumor microenvironment limit its effectiveness. Formononetin—extracted from the Chinese medicinal plant Astragalus membranaceus—can inhibit tumor growth, induce apoptosis and angiogenesis, and reverse multidrug resistance. However, its efficacy and mechanism of action on the immune cells in breast cancer remain unclear. Here, we screened immune-related genes of breast cancer to determine the potential of formononetin as a therapeutic. Methods GSE103512 and GSE139038 breast cancer microarray data and immune-related gene data were obtained from the GEO and ImmPort databases, respectively, to analyze the differentially expressed immune-related genes (IRGs) in breast cancer tissues compared with normal breast tissues. Protein-protein interaction (PPI) analysis was performed using the STRING database to screen differentially expressed IRGs based on the topological parameters. The Kaplan–Meier test was applied to detect differentially expressed IRGs associated with breast cancer survival, and the interaction of formononetin with differentially expressed IRGs was analyzed using molecular docking. Finally, the relationship between differentially expressed IRGs and breast cancer immune cell infiltration was analyzed using the TIMER2.0 database. Results A total of 29 differentially expressed IRGs of breast cancer were screened through GEO and ImmPort databases and 10 key differentially expressed IRGs based on the topological parameters from the PPI network. Among these, CXCL12, ESR1, IGF1, and FOS were associated with breast cancer survival. Furthermore, IGF1, ESR1, and CXCL12 were found to have stable binding sites for formononetin. These genes were associated with substantial immune cell infiltration in breast cancer tissues. Conclusion In conclusion, formononetin may exert antitumor effects by acting on CXCL12, ESR1, and IGF1 and may have a potential synergistic effect with immune checkpoint inhibitors.
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Vasiljević S, Mikulić M, Aćimović M, Kiprovski B, Krstić S, Katanski S, Mamlić Z. Isoflavones profiles of red clover (Trifolium pratense L.) at different growth stages. MAKEDONSKO FARMACEVTSKI BILTEN 2022. [DOI: 10.33320/10.33320/maced.pharm.bull.2020.66.04.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Affiliation(s)
- Sanja Vasiljević
- Institute of Field and Vegetable Crops, Maksima Gorkog 30, 21000, Novi Sad, Republic of Serbia
| | - Mira Mikulić
- Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000, Novi Sad, Republic of Serbia
| | - Milica Aćimović
- Institute of Field and Vegetable Crops, Maksima Gorkog 30, 21000, Novi Sad, Republic of Serbia
| | - Biljana Kiprovski
- Institute of Field and Vegetable Crops, Maksima Gorkog 30, 21000, Novi Sad, Republic of Serbia
| | - Sanja Krstić
- Faculty of Science, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Republic of Serbia
| | - Snežana Katanski
- Institute of Field and Vegetable Crops, Maksima Gorkog 30, 21000, Novi Sad, Republic of Serbia
| | - Zlatica Mamlić
- Institute of Field and Vegetable Crops, Maksima Gorkog 30, 21000, Novi Sad, Republic of Serbia
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Ma X, Li X, Ma L, Chen Y, He S. Soy isoflavones alleviate polycystic ovary syndrome in rats by regulating NF- κB signaling pathway. Bioengineered 2021; 12:7215-7223. [PMID: 34546841 PMCID: PMC8806892 DOI: 10.1080/21655979.2021.1979864] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 09/07/2021] [Accepted: 09/08/2021] [Indexed: 12/02/2022] Open
Abstract
Soy isoflavones have been widely used in the treatment of clinical gynecological diseases. The aim of this study was to investigate the therapeutic effect and molecular mechanism of Soy isoflavones on rats with polycystic ovary syndrome (PCOS). Sprague-Dawley rats were orally administered 1 mg/kg letrozole for 21 consecutive days to induce the PCOS rat model. After PCOS induction, Soy isoflavones (100 mg/kg) or metformin (Positive control; 500 mg/kg) was administered continuously for 28 days. Then, H&E staining was used to observe the pathological changes of ovary. The serum hormone levels and the levels of antioxidant and inflammatory cytokines in ovarian tissue were detected. Additionally, the expression of NF-κB signaling pathway protein was detected by Western blot. Our results showed that soy isoflavones treatment significantly reduced the body weight, ovarian volume and weight, and improved estrous cycle in PCOS rats. H&E staining showed that the number of cystic dilated follicles and atretic follicles in ovarian tissue diminished, showing healthy follicles and corpus luteum. In addition, soy isoflavones treatment markedly decreased serum testosterone and luteinizing hormone (LH) levels, as well as oxidative stress levels and inflammation levels, and increased estradiol (E2) and follicle stimulating hormone (FSH) levels. At the same time, Soy isoflavones treatment inhibit the phosphorylation level of NF-κB p65 and increased the IκBα expression in ovarian tissues of PCOS rats. Overall, Soy isoflavones can improve ovarian morphology and hormone disorders in PCOS rats by inhibiting the activity of NF-κB pathway and enhancing anti-inflammatory and antioxidant capacity.
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Affiliation(s)
- Xiaohong Ma
- The Center for Reproductive Medicine, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Xiaorong Li
- The Center for Reproductive Medicine, General Hospital of Ningxia Medical University, Yinchuan, China
| | - LiLi Ma
- The Center for Reproductive Medicine, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Yan Chen
- The Center for Reproductive Medicine, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Shengyu He
- Department of Gynecology and Obstetrics, Shizuishan Central Hospital, the Fifth People’ S Hospital of Ningxia, Shizuishan City, China
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Solopov P, Colunga Biancatelli RML, Dimitropoulou C, Catravas JD. Dietary Phytoestrogens Ameliorate Hydrochloric Acid-Induced Chronic Lung Injury and Pulmonary Fibrosis in Mice. Nutrients 2021; 13:3599. [PMID: 34684599 PMCID: PMC8536981 DOI: 10.3390/nu13103599] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 10/11/2021] [Accepted: 10/12/2021] [Indexed: 11/16/2022] Open
Abstract
We previously reported that female mice exhibit protection against chemically induced pulmonary fibrosis and suggested a potential role of estrogen. Phytoestrogens act, at least in part, via stimulation of estrogen receptors; furthermore, compared to residents of Western countries, residents of East Asian countries consume higher amounts of phytoestrogens and exhibit lower rates of pulmonary fibrosis. Therefore, we tested the hypothesis that dietary phytoestrogens ameliorate the severity of experimentally induced pulmonary fibrosis. Male mice placed on either regular soybean diet or phytoestrogen-free diet were instilled with 0.1 N HCl to provoke pulmonary fibrosis. Thirty days later, lung mechanics were measured as indices of lung function and bronchoalveolar lavage fluid (BALF) and lung tissue were analyzed for biomarkers of fibrosis. Mice on phytoestrogen-free diet demonstrated increased mortality and stronger signs of chronic lung injury and pulmonary fibrosis, as reflected in the expression of collagen, extracellular matrix deposition, histology, and lung mechanics, compared to mice on regular diet. We conclude that dietary phytoestrogens play an important role in the pathogenesis of pulmonary fibrosis and suggest that phytoestrogens (e.g., genistein) may be useful as part of a therapeutic regimen against hydrochloric acid-induced lung fibrosis and chronic lung dysfunction.
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Affiliation(s)
- Pavel Solopov
- Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508, USA; (R.M.L.C.B.); (C.D.); (J.D.C.)
| | | | - Christiana Dimitropoulou
- Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508, USA; (R.M.L.C.B.); (C.D.); (J.D.C.)
| | - John D. Catravas
- Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508, USA; (R.M.L.C.B.); (C.D.); (J.D.C.)
- School of Medical Diagnostic & Translational Sciences, College of Health Sciences, Old Dominion University, Norfolk, VA 23508, USA
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Dulce-María DA, Adrián CR, Cuauhtémoc RM, Ada-Keila MN, Jorge MC, Erika AS, Edith-Oliva CR. Isoflavones from black chickpea ( Cicer arietinum L) sprouts with antioxidant and antiproliferative activity. Saudi J Biol Sci 2021; 28:1141-1146. [PMID: 33424409 PMCID: PMC7783802 DOI: 10.1016/j.sjbs.2020.11.048] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 11/09/2020] [Accepted: 11/10/2020] [Indexed: 12/17/2022] Open
Abstract
Black chickpea is a good source of bioactive compounds, particularly isoflavones. Sprouting improves nutraceutical value in chickpea seeds. This study aimed to explore the role of sprouting of black chickpea seeds on the synthesis of isoflavones and evaluate the impact of the soluble isoflavone on cellular antioxidant activity (CAA) and antiproliferative activity in breast cancer cells. Isoflavones were identified and quantified by HPLC-UV-MS. The CAA and antiproliferative activity were determined in HepG2 cells and MDA-MB-231 cancer cells, correspondingly. In sprouted black chickpea, six isoflavones (formononetin, biochanin-A, and its glycosides) were identified and the total isoflavones content increased (0.31 to 35.72 µgBA/mg of extract). The CAA was increased five times from 137.2 to 788.2 µMEQ/100 g of sample. The bioactive compounds in sprouted chickpea decreased the proliferation of MDA-MB-231 cell line. Also caused morphological changes such as cell shrinkage, rounding and nuclear fragmentation. The results herein suggest that bioactive compounds, as isoflavones, in sprouted black chickpea showed a potential antioxidant and antiproliferative activity. Therefore, it may be considered as a value-added product or ingredient for produce functional foods.
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Affiliation(s)
- Domínguez-Arispuro Dulce-María
- Programa Regional de Posgrado en Biotecnología, Programa de Posgrado en Ciencia y Tecnología de Alimentos, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Mexico
| | - Canizalez-Román Adrián
- Programa Regional de Posgrado en Biotecnología, Programa de Posgrado en Ciencia y Tecnología de Alimentos, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Mexico.,CIASaP, Programa de Posgrado en Ciencias en Biomedicina Molecular, Facultad de Medicina, Universidad Autónoma de Sinaloa, 80246 Culiacán Sinaloa, Mexico
| | - Reyes-Moreno Cuauhtémoc
- Programa Regional de Posgrado en Biotecnología, Programa de Posgrado en Ciencia y Tecnología de Alimentos, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Mexico
| | - Milán-Noris Ada-Keila
- Programa Regional de Posgrado en Biotecnología, Programa de Posgrado en Ciencia y Tecnología de Alimentos, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Mexico
| | - Milán-Carrillo Jorge
- Programa Regional de Posgrado en Biotecnología, Programa de Posgrado en Ciencia y Tecnología de Alimentos, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Mexico
| | - Acosta-Smith Erika
- CIASaP, Programa de Posgrado en Ciencias en Biomedicina Molecular, Facultad de Medicina, Universidad Autónoma de Sinaloa, 80246 Culiacán Sinaloa, Mexico
| | - Cuevas-Rodríguez Edith-Oliva
- Programa Regional de Posgrado en Biotecnología, Programa de Posgrado en Ciencia y Tecnología de Alimentos, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Mexico
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Laborda-Illanes A, Sanchez-Alcoholado L, Dominguez-Recio ME, Jimenez-Rodriguez B, Lavado R, Comino-Méndez I, Alba E, Queipo-Ortuño MI. Breast and Gut Microbiota Action Mechanisms in Breast Cancer Pathogenesis and Treatment. Cancers (Basel) 2020; 12:E2465. [PMID: 32878124 PMCID: PMC7565530 DOI: 10.3390/cancers12092465] [Citation(s) in RCA: 110] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 08/25/2020] [Accepted: 08/27/2020] [Indexed: 12/11/2022] Open
Abstract
In breast cancer (BC) the employment of sequencing technologies for metagenomic analyses has allowed not only the description of the overall metagenomic landscape but also the specific microbial changes and their functional implications. Most of the available data suggest that BC is related to bacterial dysbiosis in both the gut microenvironment and breast tissue. It is hypothesized that changes in the composition and functions of several breast and gut bacterial taxa may contribute to BC development and progression through several pathways. One of the most prominent roles of gut microbiota is the regulation of steroid-hormone metabolism, such as estrogens, a component playing an important role as risk factor in BC development, especially in postmenopausal women. On the other hand, breast and gut resident microbiota are the link in the reciprocal interactions between cancer cells and their local environment, since microbiota are capable of modulating mucosal and systemic immune responses. Several in vivo and in vitro studies show remarkable evidence that diet, probiotics and prebiotics could exert important anticarcinogenic effects in BC. Moreover, gut microbiota have an important role in the metabolism of chemotherapeutic drugs and in the activity of immunogenic chemotherapies since they are a potential dominant mediator in the response to cancer therapy. Then, the microbiome impact in BC is multi-factorial, and the gut and breast tissue bacteria population could be important in regulating the local immune system, in tumor formation and progression and in therapy response and/or resistance.
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Affiliation(s)
- Aurora Laborda-Illanes
- Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-CIMES-UMA, 29010 Málaga, Spain; (A.L.-I.); (L.S.-A.); (M.E.D.-R.); (B.J.-R.); (R.L.); (I.C.-M.)
- Facultad de Medicina, Universidad de Málaga, 29071 Málaga, Spain
| | - Lidia Sanchez-Alcoholado
- Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-CIMES-UMA, 29010 Málaga, Spain; (A.L.-I.); (L.S.-A.); (M.E.D.-R.); (B.J.-R.); (R.L.); (I.C.-M.)
- Facultad de Medicina, Universidad de Málaga, 29071 Málaga, Spain
| | - María Emilia Dominguez-Recio
- Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-CIMES-UMA, 29010 Málaga, Spain; (A.L.-I.); (L.S.-A.); (M.E.D.-R.); (B.J.-R.); (R.L.); (I.C.-M.)
| | - Begoña Jimenez-Rodriguez
- Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-CIMES-UMA, 29010 Málaga, Spain; (A.L.-I.); (L.S.-A.); (M.E.D.-R.); (B.J.-R.); (R.L.); (I.C.-M.)
| | - Rocío Lavado
- Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-CIMES-UMA, 29010 Málaga, Spain; (A.L.-I.); (L.S.-A.); (M.E.D.-R.); (B.J.-R.); (R.L.); (I.C.-M.)
| | - Iñaki Comino-Méndez
- Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-CIMES-UMA, 29010 Málaga, Spain; (A.L.-I.); (L.S.-A.); (M.E.D.-R.); (B.J.-R.); (R.L.); (I.C.-M.)
| | - Emilio Alba
- Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-CIMES-UMA, 29010 Málaga, Spain; (A.L.-I.); (L.S.-A.); (M.E.D.-R.); (B.J.-R.); (R.L.); (I.C.-M.)
| | - María Isabel Queipo-Ortuño
- Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-CIMES-UMA, 29010 Málaga, Spain; (A.L.-I.); (L.S.-A.); (M.E.D.-R.); (B.J.-R.); (R.L.); (I.C.-M.)
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12
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Heras-González L, Latorre J, Martinez-Bebia M, Espino D, Olea-Serrano F, Mariscal-Arcas M. The relationship of obesity with lifestyle and dietary exposure to endocrine-disrupting chemicals. Food Chem Toxicol 2020; 136:110983. [DOI: 10.1016/j.fct.2019.110983] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2019] [Revised: 11/14/2019] [Accepted: 11/17/2019] [Indexed: 01/28/2023]
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Sanaei M, Kavoosi F, Dehghani F. Comparative Analysis of the Effects of 17-Beta Estradiol on Proliferation, and Apoptosis in Hepatocellular Carcinoma Hep G2 and LCL-PI 11 Cell Lines. Asian Pac J Cancer Prev 2018; 19:2637-2641. [PMID: 30256559 PMCID: PMC6249463 DOI: 10.22034/apjcp.2018.19.9.2637] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Background: Phytoestrogens are a group of natural compounds with estrogen-like activity and similar structure to estradiol that structurally mimic the mammalian estrogen 17-β estradiol (E2). They have a biphasic effect and exert pleiotropic effects which induce or inhibit estrogen action by activation/inhibition of the estrogen receptors (ERs). These compounds can induce apoptosis at high concentrations. The previous finding indicated that E2 inhibited cell growth and induced apoptosis in hepatocellular carcinoma (HCC) PLC/PRF/5 cell line. The aim of the present study was to investigate the apoptotic and proliferative effects of E2 on hepatocellular carcinoma HepG 2 and LCL-PI 11 cells. Methods: The Hep G2 and LCL-PI 11 cells were cultured and treated with E2 for different time periods and then MTT [3-(4, 5-dimethyl-2-thiazolyl) -2, 5-diphenyl -2H- tetrazolium bromide] assay and flow cytometry assay were done to determine cell viability and cell apoptosis respectively. Results: E2 had inhibitory and apoptotic effects on Hep G2 cell line, whereas it indicated a biphasic effect on LCL-PI 11 cell line. The half-maximum inhibitory concentration (IC50) value was 3 μM. The inhibitory effect of E2 on Hep G2 cells was observed with all concentrations of E2 (P <0.087), whereas E2 showed a biphasic effect on LCL-PI 11. This compound induced significant apoptosis in Hep G2 cell line at the all treatment times versus control groups, whereas, in the LCL-PI 11 cell, significant apoptotic cells were observed after 72 and 96h (P <0.001). Conclusion: E2 can inhibit cell growth and induce apoptosis in hepatocellular carcinoma HepG 2 and LCL-PI 11 cell lines.
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Affiliation(s)
- Masumeh Sanaei
- Research Center for Non- Communicable Diseases, Jahrom University of Medical Sciences, Jahrom, Iran.
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14
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Amaral C, Toloi MRT, Vasconcelos LD, Fonseca MJV, Correia-da-Silva G, Teixeira N. The role of soybean extracts and isoflavones in hormone-dependent breast cancer: aromatase activity and biological effects. Food Funct 2017; 8:3064-3074. [PMID: 28644496 DOI: 10.1039/c7fo00205j] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2023]
Abstract
Estrogen receptor-positive (ER+) breast cancer is the most common cause of cancer death in women worldwide. Nowadays, the relationship between soya diet and breast cancer is controversial due to the unknown role of its isoflavones, genistein (G) and daidzein (D). In this work, we investigated not only the anti-tumor properties of a soybean extract (NBSE) but also whether the biotransformation of extract (BSE) by the fungus Aspergillus awamori increased its effectiveness. The BSE showed a stronger anti-aromatase activity and anti-proliferative efficacy in ER+ aromatase-overexpressing breast cancer cells. D and G were weak aromatase inhibitors, but inhibited cancer cell growth, being G the isoflavone that contributed to the BSE-induced effects. This work demonstrated that the biotransformation increased the anti-aromatase activity and the anti-tumoral efficacy of soybean extract in breast cancer cells. Moreover, it elucidated the potential use of soya in the prevention and/or treatment of ER+ breast cancer.
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Affiliation(s)
- Cristina Amaral
- UCIBIO.REQUIMTE, Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
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15
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Zhang FF, Haslam DE, Terry MB, Knight JA, Andrulis IL, Daly MB, Buys SS, John EM. Dietary isoflavone intake and all-cause mortality in breast cancer survivors: The Breast Cancer Family Registry. Cancer 2017; 123:2070-2079. [PMID: 28263368 DOI: 10.1002/cncr.30615] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2016] [Accepted: 09/08/2016] [Indexed: 01/09/2023]
Abstract
BACKGROUND Soy foods possess both antiestrogenic and estrogen-like properties. It remains controversial whether women diagnosed with breast cancer should be advised to eat more or less soy foods, especially for those who receive hormone therapies as part of cancer treatment. METHODS The association of dietary intake of isoflavone, the major phytoestrogen in soy, with all-cause mortality was examined in 6235 women with breast cancer enrolled in the Breast Cancer Family Registry. Dietary intake was assessed using a Food Frequency Questionnaire developed for the Hawaii-Los Angeles Multiethnic Cohort among 5178 women who reported prediagnosis diet and 1664 women who reported postdiagnosis diet. Cox proportional-hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS During a median follow-up of 113 months (approximately 9.4 years), 1224 deaths were documented. A 21% decrease was observed in all-cause mortality for women who had the highest versus lowest quartile of dietary isoflavone intake (≥1.5 vs < 0.3 mg daily: HR, 0.79; 95% confidence interval CI, 0.64-0.97; Ptrend = .01). Lower mortality associated with higher intake was limited to women who had tumors that were negative for hormone receptors (HR, 0.49; 95% CI, 0.29-0.83; Ptrend = .005) and those who did not receive hormone therapy for their breast cancer (HR, 0.68; 95% CI, 0.51-0.91; Ptrend = .02). Interactions, however, did not reach statistical significance. CONCLUSIONS In this large, ethnically diverse cohort of women with breast cancer living in North America, a higher dietary intake of isoflavone was associated with reduced all-cause mortality. Cancer 2017;123:2070-2079. © 2017 American Cancer Society.
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Affiliation(s)
- Fang Fang Zhang
- Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts
| | - Danielle E Haslam
- Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts
| | - Mary Beth Terry
- Mailman School of Public Health, Columbia University, New York, New York
| | - Julia A Knight
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.,Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Irene L Andrulis
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.,Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Mary B Daly
- Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Saundra S Buys
- Huntsman Cancer Institute at the University of Utah Health Sciences Center, Salt Lake City, Utah
| | - Esther M John
- Cancer Prevention Institute of California, Fremont, California.,Department of Health Research and Policy (Epidemiology) and Stanford Cancer Institute, Stanford University of School of Medicine, Stanford, California
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de Amorim Ribeiro IC, da Costa CAS, da Silva VAP, Côrrea LBNS, Boaventura GT, Chagas MA. Flaxseed reduces epithelial proliferation but does not affect basal cells in induced benign prostatic hyperplasia in rats. Eur J Nutr 2016; 56:1201-1210. [PMID: 26857761 DOI: 10.1007/s00394-016-1169-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Accepted: 01/29/2016] [Indexed: 02/04/2023]
Abstract
PURPOSE This study aimed to quantitatively and qualitatively evaluate the effects of a flaxseed-based diet on the histoarchitecture of the prostate of normal Wistar rats and of rats with induced BPH. METHODS The study included four experimental groups of ten animals each: casein control group (CCG), who were fed a casein-based diet; flaxseed control group (FCG), who were fed a flaxseed-based diet; hyperplasia-induced casein group (HICG), who were fed a casein-based diet; and hyperplasia-induced flaxseed group (HIFG), who were fed a flaxseed-based diet. Hyperplasia was induced by the subcutaneous implantation of silicone pellets containing testosterone propionate. After 20 weeks, the rats were euthanized and their prostate fixed in buffered formalin. Tissue sections were stained with HE, picrosirius red and immunostained for nuclear antigen p63. Histomorphometric analysis evaluated the epithelial thickness, epithelial area, individual luminal area, and total area of prostatic alveoli. RESULTS The mean epithelial thickness obtained for HIFG and HICG was 16.52 ± 1.65 and 20.58 ± 2.86 µm, respectively. The mean epithelial thickness in HICG was greater than that in the other groups tested. HIFG had a smaller epithelial thickness and lower percentage of papillary projections in the prostatic alveoli. No significant difference was observed between CCG and FCG. The total area and mean alveolar area showed no significant differences between the groups. The number of cells immunostained for p63 was not significantly different between the groups evaluated. CONCLUSION These results suggest that flaxseed has a protective effect on the prostate epithelium in BPH-induced animals.
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Affiliation(s)
- Ilma Cely de Amorim Ribeiro
- Department of Morphology, Laboratory of Cellular and Extracellular Biomorphology Biomedic Institute, Federal Fluminense University, Rua Hernani Melo, 101, São Domingos, Niterói, Rio de Janeiro, RJ, 24210-130, Brazil
| | - Carlos Alberto Soares da Costa
- Department of Nutrition and Dietetics, Experimental Nutrition Laboratory, College of Nutrition, Federal Fluminense University, 30/5th floor, Rio de Janeiro, 24020-140, Brazil
| | - Vivian Alves Pereira da Silva
- Department of Morphology, Laboratory of Cellular and Extracellular Biomorphology Biomedic Institute, Federal Fluminense University, Rua Hernani Melo, 101, São Domingos, Niterói, Rio de Janeiro, RJ, 24210-130, Brazil
| | - Lanna Beatriz Neves Silva Côrrea
- Department of Morphology, Laboratory of Cellular and Extracellular Biomorphology Biomedic Institute, Federal Fluminense University, Rua Hernani Melo, 101, São Domingos, Niterói, Rio de Janeiro, RJ, 24210-130, Brazil
| | - Gilson Teles Boaventura
- Department of Nutrition and Dietetics, Experimental Nutrition Laboratory, College of Nutrition, Federal Fluminense University, 30/5th floor, Rio de Janeiro, 24020-140, Brazil
| | - Mauricio Alves Chagas
- Department of Morphology, Laboratory of Cellular and Extracellular Biomorphology Biomedic Institute, Federal Fluminense University, Rua Hernani Melo, 101, São Domingos, Niterói, Rio de Janeiro, RJ, 24210-130, Brazil.
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Bilal I, Chowdhury A, Davidson J, Whitehead S. Phytoestrogens and prevention of breast cancer: The contentious debate. World J Clin Oncol 2014; 5:705-712. [PMID: 25302172 PMCID: PMC4129534 DOI: 10.5306/wjco.v5.i4.705] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2013] [Revised: 01/26/2014] [Accepted: 05/19/2014] [Indexed: 02/06/2023] Open
Abstract
Phytoestrogens have multiple actions within target cells, including the epigenome, which could be beneficial to the development and progression of breast cancer. In this brief review the action of phytoestrogens on oestrogen receptors, cell signalling pathways, regulation of the cell cycle, apoptosis, steroid synthesis and epigenetic events in relation to breast cancer are discussed. Phytoestrogens can bind weakly to oestrogen receptors (ERs) and some have a preferential affinity for ERβ which can inhibit the transcriptional growth-promoting activity of ERα. However only saturating doses of phytoestrogens, stimulating both ERα and β, exert growth inhibitory effects. Such effects on growth may be through phytoestrogens inhibiting cell signalling pathways. Phytoestrogens have also been shown to inhibit cyclin D1 expression but increase the expression of cyclin-dependent kinase inhibitors (p21 and p27) and the tumour suppressor gene p53. Again these effects are only observed at high (> 10) µmol/L doses of phytoestrogens. Finally the effects of phytoestrogens on breast cancer may be mediated by their ability to inhibit local oestrogen synthesis and induce epigenetic changes. There are, though, difficulties in reconciling epidemiological and experimental data due to the fact experimental doses, both in vivo and in vitro, far exceed the circulating concentrations of “free” unbound phytoestrogens measured in women on a high phytoestrogen diet or those taking phytoestrogen supplements.
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Hsieh CJ, Kuo PL, Hsu YC, Huang YF, Tsai EM, Hsu YL. Arctigenin, a dietary phytoestrogen, induces apoptosis of estrogen receptor-negative breast cancer cells through the ROS/p38 MAPK pathway and epigenetic regulation. Free Radic Biol Med 2014; 67:159-70. [PMID: 24140706 DOI: 10.1016/j.freeradbiomed.2013.10.004] [Citation(s) in RCA: 114] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2013] [Revised: 09/13/2013] [Accepted: 10/02/2013] [Indexed: 12/31/2022]
Abstract
This study investigates the anticancer effect of arctigenin (ATG), a natural lignan product of Arctium lappa L., in human breast cancer MDA-MB-231 cells. Results indicate that ATG inhibits MDA-MB-231 cell growth by inducing apoptosis in vitro and in vivo. ATG triggers the mitochondrial caspase-independent pathways, as indicated by changes in Bax/Bcl-2 ratio, resulting in AIF and EndoG nuclear translocation. ATG increased cellular reactive oxygen species (ROS) production by increasing p22(phox)/NADPH oxidase 1 interaction and decreasing glutathione level. ATG clearly increases the activation of p38 MAPK, but not JNK and ERK1/2. Antioxidant EUK-8, a synthetic catalytic superoxide and hydrogen peroxide scavenger, significantly decreases ATG-mediated p38 activation and apoptosis. Blocking p38 with a specific inhibitor suppresses ATG-mediated Bcl-2 downregulation and apoptosis. Moreover, ATG activates ATF-2, a transcription factor activated by p38, and then upregulates histone H3K9 trimethylation in the Bcl-2 gene promoter region, resulting in Bcl-2 downregulation. Taken together, the results demonstrate that ATG induces apoptosis of MDA-MB-231 cells via the ROS/p38 MAPK pathway and epigenetic regulation of Bcl-2 by upregulation of histone H3K9 trimethylation.
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Affiliation(s)
- Chia-Jung Hsieh
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Department of Chinese Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
| | - Po-Lin Kuo
- Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
| | - Ying-Chan Hsu
- Department of Chinese Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
| | - Ya-Fang Huang
- Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
| | - Eing-Mei Tsai
- Center for Resources, Research, and Development, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Department of Obstetrics & Gynecology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
| | - Ya-Ling Hsu
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
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Chi F, Wu R, Zeng YC, Xing R, Liu Y, Xu ZG. Post-diagnosis soy food intake and breast cancer survival: a meta-analysis of cohort studies. Asian Pac J Cancer Prev 2013; 14:2407-12. [PMID: 23725149 DOI: 10.7314/apjcp.2013.14.4.2407] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Data on associations between soy food intake after cancer diagnosis with breast cancer survival are conflicting, so we conducted this meta-analysis for more accurate evaluation. METHODS Comprehensive searches were conducted to find cohort studies of the relationship between soy food intake after cancer diagnosis and breast cancer survival. Data were analyzed with comprehensive meta-analysis software. RESULTS Five cohort studies (11,206 patients) were included. Pooling all comparisons, soy food intake after diagnosis was associated with reduced mortality (HR 0.85, 95%CI 0.77 0.93) and recurrence (HR 0.79, 95%CI 0.72 0.87). Pooling the comparisons of highest vs. lowest dose, soy food intake after diagnosis was again associated with reduced mortality (HR 0.84, 95%CI 0.71 0.99) and recurrence (HR 0.74, 95%CI 0.64 0.85). Subgroup analysis of ER status showed that soy food intake was associated with reduced mortality in both ER negative (highest vs. lowest: HR 0.75, 95%CI 0.64 0.88) and ER positive patients (highest vs. lowest: HR 0.72, 95%CI 0.61 0.84), and both premenopausal (highest vs. lowest: HR 0.78, 95%CI 0.69 0.88) and postmenopausal patients (highest vs. lowest: HR 0.81, 95%CI 0.73 0.91). In additioin, soy food intake was associated with reduced recurrence in ER negative (highest vs. lowest: HR 0.64, 95%CI 0.44 0.94) and ER+/PR+ (highest vs. lowest: HR 0.65, 95%CI 0.49 0.86), and postmenopausal patients (highest vs. lowest: HR 0.67, 95%CI 0.56 0.80). CONCLUSION Our meta- analysis showed that soy food intake might be associated with better survival, especially for ER negative, ER+/ PR+, and postmenopausal patients.
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Affiliation(s)
- Feng Chi
- Department of Medical Oncology, Shengjing Hospital of China Medical University, Shenyang, China.
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Richter D, Abarzua S, Chrobak M, Vrekoussis T, Weissenbacher T, Kuhn C, Schulze S, Kupka MS, Friese K, Briese V, Piechulla B, Makrigiannakis A, Jeschke U, Dian D. Effects of Phytoestrogen Extracts Isolated from Pumpkin Seeds on Estradiol Production and ER/PR Expression in Breast Cancer and Trophoblast Tumor Cells. Nutr Cancer 2013; 65:739-45. [DOI: 10.1080/01635581.2013.797000] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Swann R, Perkins KA, Velentzis LS, Ciria C, Dutton SJ, Mulligan AA, Woodside JV, Cantwell MM, Leathem AJ, Robertson CE, Dwek MV. The DietCompLyf study: a prospective cohort study of breast cancer survival and phytoestrogen consumption. Maturitas 2013; 75:232-40. [PMID: 23664318 DOI: 10.1016/j.maturitas.2013.03.018] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2013] [Revised: 03/28/2013] [Accepted: 03/30/2013] [Indexed: 11/12/2022]
Abstract
DietCompLyf is a multi-centre prospective study designed to investigate associations between phytoestrogens - naturally occurring plant compounds with oestrogenic properties - and other diet and lifestyle factors with breast cancer recurrence and survival. 3159 women with grades I-III breast cancer were recruited 9-15 months post-diagnosis from 56 UK hospitals. Detailed information on clinico-pathological, diet, lifestyle and quality of life is collected annually up to 5 years. Biological samples have also been collected as a resource for subsequent evaluation. The characteristics of the patients and associations between pre-diagnosis intake of phytoestrogens (isoflavones and lignans; assessed using the EPIC-Norfolk UK 130 question food frequency questionnaire) and breast cancer (i) risk factors and (ii) prognostic factors are described for 1797 women who had complete data for all covariates and phytoestrogens of interest. Isoflavone intakes were higher in the patients who were younger at diagnosis, in the non-smokers, those who had breast-fed and those who took supplements. Lignan intakes were higher in patients with a higher age at diagnosis, in ex-smokers, those who had breast-fed, who took supplements, had a lower BMI at diagnosis, lower age at menarche and were nulliparous. No significant associations between pre-diagnosis phytoestrogen intake and factors associated with improved breast cancer prognosis were observed. The potential for further exploration of the relationship between phytoestrogens and breast cancer recurrence and survival, and for the establishment of evidence to improve dietary and lifestyle advice offered to patients following breast cancer diagnosis using DietCompLyf data is discussed.
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Affiliation(s)
- Ruth Swann
- Departments of Molecular and Applied Biosciences and Human and Health Sciences, University of Westminster, 115 New Cavendish St., London, UK
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Zamora-Ros R, Ferrari P, González CA, Tjønneland A, Olsen A, Bredsdorff L, Overvad K, Touillaud M, Perquier F, Fagherazzi G, Lukanova A, Tikk K, Aleksandrova K, Boeing H, Trichopoulou A, Trichopoulos D, Dilis V, Masala G, Sieri S, Mattiello A, Tumino R, Ricceri F, Bueno-de-Mesquita HB, Peeters PHM, Weiderpass E, Skeie G, Engeset D, Menéndez V, Travier N, Molina-Montes E, Amiano P, Chirlaque MD, Barricarte A, Wallström P, Sonestedt E, Sund M, Landberg R, Khaw KT, Wareham NJ, Travis RC, Scalbert A, Ward HA, Riboli E, Romieu I. Dietary flavonoid and lignan intake and breast cancer risk according to menopause and hormone receptor status in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. Breast Cancer Res Treat 2013; 139:163-76. [PMID: 23572295 DOI: 10.1007/s10549-013-2483-4] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2013] [Accepted: 03/11/2013] [Indexed: 10/27/2022]
Abstract
Evidence on the association between dietary flavonoids and lignans and breast cancer (BC) risk is inconclusive, with the possible exception of isoflavones in Asian countries. Therefore, we investigated prospectively dietary total and subclasses of flavonoid and lignan intake and BC risk according to menopause and hormonal receptor status in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 334,850 women, mostly aged between 35 and 70 years from ten European countries. At baseline, country-specific validated dietary questionnaires were used. A flavonoid and lignan food composition database was developed from the US Department of Agriculture, the Phenol-Explorer and the UK Food Standards Agency databases. Cox regression models were used to analyse the association between dietary flavonoid/lignan intake and the risk of developing BC. During an average 11.5-year follow-up, 11,576 incident BC cases were identified. No association was observed between the intake of total flavonoids [hazard ratio comparing fifth to first quintile (HRQ5-Q1) 0.97, 95 % confidence interval (CI): 0.90-1.04; P trend = 0.591], isoflavones (HRQ5-Q1 1.00, 95 % CI: 0.91-1.10; P trend = 0.734), or total lignans (HRQ5-Q1 1.02, 95 % CI: 0.93-1.11; P trend = 0.469) and overall BC risk. The stratification of the results by menopausal status at recruitment or the differentiation of BC cases according to oestrogen and progesterone receptors did not affect the results. This study shows no associations between flavonoid and lignan intake and BC risk, overall or after taking into account menopausal status and BC hormone receptors.
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Affiliation(s)
- Raul Zamora-Ros
- Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Avda Gran Via 199-203, L'Hospitalet de Llobregat, 08907, Barcelona, Spain.
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Abstract
PURPOSE OF REVIEW Transformed cells exhibit a high rate of glucose consumption beyond that necessary for ATP synthesis. Glucose aids in the generation of biomass and regulates cellular signaling critical for oncogenic progression. A key rate-limiting step in glucose utilization is the transport of glucose across the plasma membrane. This review will highlight key glucose transporters (GLUTs) and current therapies targeting this class of proteins. RECENT FINDINGS GLUTs, enabling the facilitative entry of glucose into a cell, are increasingly found to be deregulated in cancer. Although cancer-specific expression patterns for GLUTs are being identified, comprehensive analyses substantiating a role for individual GLUTs are still required. Studies defining GLUTs as being rate-limiting in specific tumor contexts, the identification of GLUT1 inhibitors via synthetic lethality screens, novel engagement of the insulin-responsive GLUT4 in myeloma and identification of GLUT9 being a urate transporter, are key advances underscoring the need for continued investigation of this large and enigmatic class of proteins. SUMMARY Tumor cells exhibit elevated levels of glucose uptake, a phenomenon that has been capitalized upon for the prognostic and diagnostic imaging of a wide range of cancers using radio-labeled glucose analogs. We have, however, not yet been able to target glucose entry in a tumor cell-specific manner for therapy. GLUTs have been identified as rate-limiting in specific tumor contexts. The identification and targeting of tumor-specific GLUTs provide a promising approach to block glucose-regulated metabolism and signaling more comprehensively.
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Hernandez-Elizondo J, Monteagudo C, Murcia MA, Olea N, Olea-Serrano F, Mariscal-Arcas M. Assessment of the estrogenicity of the diet of a healthy female Spanish population based on its isoflavone content. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2013; 30:627-33. [PMID: 23506255 DOI: 10.1080/19440049.2013.775604] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Phytoestrogens are natural components of plants consumed by humans. The hormonal activity of these substances has long been known. Various in vitro tests have demonstrated the agonistic or antagonistic estrogenic activity of some phytoestrogens. The objective of this study was to estimate the supply of isoflavones in the diet of a healthy adult female population and to assess its estrogenic effect. The diet was assessed by questionnaire and the estrogenicity of the estimated isoflavone content was tested by E-screen, finding a mean total estrogenic capacity of 0.129 × 10⁻¹⁰ eq.E₂ (12.9 pmol day⁻¹), corresponding to a daily isoflavone intake of 265.8 μg day⁻¹. This study offers a preliminary insight into the phytoestrogen content of the diet of a healthy active population of Spanish women. The effects of this additional hormonal burden are highly controversial, and this approach to estimating dietary phytoestrogen intake of specific populations may help to elucidate its implications for human health.
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Affiliation(s)
- J Hernandez-Elizondo
- Research Group on Nutrition, Diet and Risk Assessment-AGR255, Department of Nutrition and Food Science, University of Granada, Granada, Spain
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Glickman-Simon R, Alper BS. Acupressure and Postoperative Vomiting, Soy and Breast Cancer, Gingko Biloba and Alzheimer's Disease, Acupuncture and Irritable Bowel Syndrome, Mediterranean and Low-Carbohydrate Diets. Explore (NY) 2013; 9:112-5. [DOI: 10.1016/j.explore.2012.12.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Pharmacological and non-hormonal treatment of hot flashes in breast cancer survivors: CEPO review and recommendations. Support Care Cancer 2013; 21:1461-74. [DOI: 10.1007/s00520-013-1732-8] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2012] [Accepted: 01/28/2013] [Indexed: 11/26/2022]
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Kiss B, Popa DS, Paltinean R, Loghin F. A HIGH-THROUGHPUT UPLC-MS/MS FOR THE SIMULTANEOUS ANALYSIS OF SIX PHYTOESTROGENS FROM GENISTA TINCTORIA EXTRACTS. J LIQ CHROMATOGR R T 2012. [DOI: 10.1080/10826076.2011.638410] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Affiliation(s)
- Béla Kiss
- a Department of Toxicology , Faculty of Pharmacy, “Iuliu Haţieganu” University of Medicine and Pharmacy , Cluj-Napoca , Romania
| | - Daniela-Saveta Popa
- a Department of Toxicology , Faculty of Pharmacy, “Iuliu Haţieganu” University of Medicine and Pharmacy , Cluj-Napoca , Romania
| | - Ramona Paltinean
- b Department of Pharmaceutical Botany , “Iuliu Haţieganu” University of Medicine and Pharmacy , Cluj-Napoca , Romania
| | - Felicia Loghin
- a Department of Toxicology , Faculty of Pharmacy, “Iuliu Haţieganu” University of Medicine and Pharmacy , Cluj-Napoca , Romania
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Seppen J. A diet containing the soy phytoestrogen genistein causes infertility in female rats partially deficient in UDP glucuronyltransferase. Toxicol Appl Pharmacol 2012; 264:335-42. [PMID: 23000043 DOI: 10.1016/j.taap.2012.09.013] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2012] [Revised: 09/12/2012] [Accepted: 09/14/2012] [Indexed: 01/09/2023]
Abstract
Soy beans contain genistein, a natural compound that has estrogenic effects because it binds the estrogen receptor with relatively high affinity. Genistein is therefore the most important environmental estrogen in the human diet. Detoxification of genistein is mediated through conjugation by UDP-glucuronyltransferase 1 and 2 (UGT1 and UGT2) isoenzymes. Gunn rats have a genetic deficiency in UGT1 activity, UGT2 activities are not affected. Because our Gunn rats stopped breeding after the animal chow was changed to a type with much higher soy content, we examined the mechanism behind this soy diet induced infertility. Gunn and control rats were fed diets with and without genistein. In these rats, plasma levels of genistein and metabolites, fertility and reproductive parameters were determined. Enzyme assays showed reduced genistein UGT activity in Gunn rats, as compared to wild type rats. Female Gunn rats were completely infertile on a genistein diet, wild type rats were fertile. Genistein diet caused a persistent estrus, lowered serum progesterone and inhibited development of corpora lutea in Gunn rats. Concentrations of total genistein in Gunn and control rat plasma were identical and within the range observed in humans after soy consumption. However, Gunn rat plasma contained 25% unconjugated genistein, compared to 3.6% in control rats. This study shows that, under conditions of reduced glucuronidation, dietary genistein exhibits a strongly increased estrogenic effect. Because polymorphisms that reduce UGT1 expression are prevalent in the human population, these results suggest a cautionary attitude towards the consumption of large amounts of soy or soy supplements.
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Affiliation(s)
- Jurgen Seppen
- Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, S1-166, Meibergdreef 69, 1105 BK Amsterdam, The Netherlands.
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Zander SAL, Kersbergen A, Sol W, Gonggrijp M, van de Wetering K, Jonkers J, Borst P, Rottenberg S. Lack of ABCG2 shortens latency of BRCA1-deficient mammary tumors and this is not affected by genistein or resveratrol. Cancer Prev Res (Phila) 2012; 5:1053-60. [PMID: 22767648 DOI: 10.1158/1940-6207.capr-12-0050] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
In addition to their role in drug resistance, the ATP-binding cassette (ABC) transporters ABCG2 and ABCB1 have been suggested to protect cells from a broad range of substances that may foster tumorigenesis. Phytoestrogens or their metabolites are substrates of these transporters and the influence of these compounds on breast cancer development is controversial. Estrogen-like properties might accelerate tumorigenesis on the one hand, whereas their proposed health-protective properties might antagonize tumorigenesis on the other. To address this issue, we used a newer generation mouse model of BRCA1-mutated breast cancer and examined tumor latency in K14cre;Brca1(F/F); p53(F/F), Abcb1a/b(-/-);K14cre;Brca1(F/F); p53(F/F), or Abcg2(-/-);K14cre;Brca1(F/F); p53(F/F) animals, fed with genistein- or resveratrol-supplemented diets. Ovariectomized K14cre;Brca1(F/F); p53(F/F) animals were included to evaluate whether any estrogen-mimicking effects can restore mammary tumor development in the absence of endogenous estrogens. Compared with the ABC transporter proficient model, ABCG2-deficient animals showed a reduced median tumor latency of 17.5 days (P < 0.001), whereas no significant difference was observed for ABCB1-deficient animals. Neither genistein nor resveratrol altered this latency reduction in Abcg2(-/-);K14cre;Brca1(F/F); p53(F/F) animals. Ovariectomy resulted in nearly complete loss of mammary tumor development, which was not restored by genistein or resveratrol. Our results show that ABCG2 contributes to the protection of genetically instable epithelial cells against carcinogenesis. Diets containing high levels of genistein or resveratrol had no effect on mammary tumorigenesis, whether mice were lacking ABCG2 or not. Because genistein and resveratrol only delayed skin tumor development of ovariectomized animals, we conclude that these phytoestrogens are no effective modulators of mammary tumor development in our mouse model.
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Affiliation(s)
- Serge A L Zander
- Division of Molecular Oncology, The Netherlands Cancer Institute (Antoni van Leeuwenhoek Hospital), Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
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Nechuta SJ, Caan BJ, Chen WY, Lu W, Chen Z, Kwan ML, Flatt SW, Zheng Y, Zheng W, Pierce JP, Shu XO. Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women. Am J Clin Nutr 2012; 96:123-32. [PMID: 22648714 PMCID: PMC3374736 DOI: 10.3945/ajcn.112.035972] [Citation(s) in RCA: 112] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Soy isoflavones have antiestrogenic and anticancer properties but also possess estrogen-like properties, which has raised concern about soy food consumption among breast cancer survivors. OBJECTIVE We prospectively evaluated the association between postdiagnosis soy food consumption and breast cancer outcomes among US and Chinese women by using data from the After Breast Cancer Pooling Project. DESIGN The analysis included 9514 breast cancer survivors with a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and 1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food-frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry Cox regression models, adjusted for sociodemographic, clinical, and lifestyle factors. RESULTS After a mean follow-up of 7.4 y, we identified 1171 total deaths (881 from breast cancer) and 1348 recurrences. Despite large differences in soy isoflavone intake by country, isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined. No heterogeneity was observed. In the pooled analysis, consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI: 0.70, 1.10) and breast cancer-specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI: 0.61, 0.92). CONCLUSION In this large study of combined data on US and Chinese women, postdiagnosis soy food consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of breast cancer-specific mortality and a statistically significant reduced risk of recurrence.
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Affiliation(s)
- Sarah J Nechuta
- Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
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McLachlan JA, Tilghman SL, Burow ME, Bratton MR. Environmental signaling and reproduction: a comparative biological and chemical perspective. Mol Cell Endocrinol 2012; 354:60-2. [PMID: 22178089 PMCID: PMC3641892 DOI: 10.1016/j.mce.2011.11.028] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2011] [Accepted: 11/28/2011] [Indexed: 01/31/2023]
Abstract
Reproduction is a critical element of life. Self-propagation in all living organisms ranging from bacteria to humans involves numerous common strategies. Underlying all reproductive strategies is the essential need for signaling molecules to initiate and maintain the process. In this paper we use comparative biological and chemical approaches to explore the origins and distribution of estrogen signaling as a pathway common to many life forms. In the process we illuminate the mechanisms whereby environmental agents alter reproduction and development. These mechanisms involve altered signaling pathways within cells and shifts in the targets of the signaling pathways to include regulators of gene transcription normally associated with other pathways. We also stress the role of signal cross talk in mediating hormone action.
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Affiliation(s)
- John A. McLachlan
- Environmental Signaling Laboratory, Tulane University, 1430 Tulane Ave., New Orleans, LA 70122, USA
- Department of Pharmacology, Tulane University School of Medicine, USA
- Department of Ecology and Evolutionary Biology, Tulane University School of Science and Engineering, USA
| | - Syreeta L. Tilghman
- Environmental Signaling Laboratory, Tulane University, 1430 Tulane Ave., New Orleans, LA 70122, USA
- Department of Pharmacology, Tulane University School of Medicine, USA
- Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA, USA
| | - Matthew E. Burow
- Department of Medicine, Division of Hematology and Oncology, Tulane University School of Medicine, USA
| | - Melyssa R. Bratton
- Environmental Signaling Laboratory, Tulane University, 1430 Tulane Ave., New Orleans, LA 70122, USA
- Department of Pharmacology, Tulane University School of Medicine, USA
- Corresponding author at: Department of Pharmacology, Tulane University,
School of Medicine, USA. Tel.: +1 504 988 6623. (M.R. Bratton)
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Seo HS, Choi HS, Kim SR, Choi YK, Woo SM, Shin I, Woo JK, Park SY, Shin YC, Ko SG, Ko SK. Apigenin induces apoptosis via extrinsic pathway, inducing p53 and inhibiting STAT3 and NFκB signaling in HER2-overexpressing breast cancer cells. Mol Cell Biochem 2012; 366:319-34. [PMID: 22527937 DOI: 10.1007/s11010-012-1310-2] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2011] [Accepted: 04/03/2012] [Indexed: 12/12/2022]
Abstract
Phytoestrogens are known to prevent tumor induction. But their molecular mechanisms of action are still unknown. This study aimed to examine the effect of apigenin on proliferation and apoptosis in HER2-expressing breast cancer cells. In our experiments, apigenin inhibited the proliferation of MCF-7 vec and MCF-7 HER2 cells. This growth inhibition was accompanied with an increase of sub G(0)/G(1) apoptotic fractions. Overexpression of HER2 did not confer resistance to apigenin in MCF-7 cells. Apigenin-induced extrinsic apoptosis pathway up-regulating the levels of cleaved caspase-8, and inducing the cleavage of poly (ADP-ribose) polymerase, whereas apigenin did not induce apoptosis via intrinsic mitochondrial apoptosis pathway since this compound did not decrease mitochondrial membrane potential maintaining red fluorescence and did not affect the levels of B-cell lymphoma 2 (BCL2) and Bcl-2-associated X protein. Moreover, apigenin reduced the tyrosine phosphorylation of HER2 (phospho-HER2 level) in MCF-7 HER2 cells, and up-regulated the levels of p53, phospho-p53 and p21 in MCF-7 vec and MCF-7 HER2 cells. This suggests that apigenin induces apoptosis through p53-dependent pathway. Apigenin also reduced the expression of phospho-JAK1 and phospho-STAT3 and decreased STAT3-dependent luciferase reporter gene activity in MCF-7 vec and MCF-7 HER2 cells. Apigenin decreased the phosphorylation level of IκBα in the cytosol, and abrogated the nuclear translocation of p65 within the nucleus suggesting that it blocks the activation of NFκB signaling pathway in MCF-7 vec and MCF-7 HER2 cells. Our study indicates that apigenin could be a potential useful compound to prevent or treat HER2-overexpressing breast cancer.
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Affiliation(s)
- Hye-Sook Seo
- Laboratory of Clinical Biology and Pharmacogenomics and Center for Clinical Research and Genomics, Institute of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea
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Zhang YF, Kang HB, Li BL, Zhang RM. Positive Effects of Soy Isoflavone Food on Survival of Breast Cancer Patients in China. Asian Pac J Cancer Prev 2012; 13:479-82. [DOI: 10.7314/apjcp.2012.13.2.479] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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Mannella P, Tosi V, Russo E, Zullino S, Pancetti F, Gompal S, Polak K, Genazzani AR, Genazzani AD, Simoncini T. Effects of red clover extracts on breast cancer cell migration and invasion. Gynecol Endocrinol 2012; 28:29-33. [PMID: 21615235 DOI: 10.3109/09513590.2011.579660] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Postmenopausal hormone therapy is associated with increased incidence of breast cancer. For this reason alternative therapeutic options to treat menopausal symptoms have been developed. Red clover extracts (RCE) are rich in isoflavones, particularly genistein and daidzein and they have been proved to be effective in reducing vasomotor symptoms in a number of studies. Due to their partial selectivity of action on estrogen receptors (ERs) these compounds have been claimed to be safer on the breast. In this article, we explored the action of RCE on motility and invasion of ER positive breast cancer cells and we partially characterized the signaling mechanisms. The principal isoflavones contained in RCE acted as weak estrogenic compounds when administered alone. However, when provided in association with physiological amounts of estradiol, RCE acted as estrogen antagonist on remodeling of actin cytoskeleton that are requested to enact cell movement and with related modifications of the activity of actin-binding proteins, such as moesin. These results offer novel information on the molecular actions of isoflavones contained in red clover on breast cancer cells, supporting a possible action of these molecules as natural selective estrogen receptor modulators in the presence of physiological amounts of estrogens.
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Affiliation(s)
- Paolo Mannella
- Department of Reproductive Medicine and Child Development , Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), University of Pisa, Pisa 56100, Italy.
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Buck K, Vrieling A, Zaineddin AK, Becker S, Hüsing A, Kaaks R, Linseisen J, Flesch-Janys D, Chang-Claude J. Serum enterolactone and prognosis of postmenopausal breast cancer. J Clin Oncol 2011; 29:3730-8. [PMID: 21900115 DOI: 10.1200/jco.2011.34.6478] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
PURPOSE Lignans--plant-derived compounds with estrogen-dependent and -independent anticarcinogenic properties--have been associated with postmenopausal breast cancer risk, but data are limited regarding their effect on survival. Dietary lignans are metabolized to enterolignans, which are subsequently absorbed and become bioavailable. PATIENTS AND METHODS We assessed the prognosis of 1,140 postmenopausal patients with breast cancer age 50 to 74 years who were diagnosed between 2002 and 2005. Vital status through the end of 2009 was ascertained via local population registries, and deaths were verified by death certificates. Information on recurrences and secondary tumors was verified by clinical records and attending physicians. Associations of postdiagnostic serum enterolactone (a biomarker for dietary lignans) with overall survival and distant disease-free survival were assessed by using Cox proportional hazards models stratified by age at diagnosis and adjusted for prognostic factors. RESULTS Median enterolactone levels for deceased patients and those still alive were 17.0 and 21.4 nmol/L, respectively. During a median of 6.1 years of follow-up after diagnosis, 162 deaths were confirmed. Higher serum enterolactone levels were associated with significantly reduced hazard ratios (HRs) for death (HR per 10 nmol/L increment, 0.94; P = .04; HR for the highest quartile, 0.58; 95% CI, 0.34 to 0.99). For distant disease, HR was 0.94 per 10 nmol/L increment (P = .08) and 0.62 (95% CI, 0.35 to 1.09) for the highest quartile. The highest quartile of serum enterolactone was associated with a significantly reduced risk of death only for estrogen receptor-negative tumors (HR, 0.27; 95% CI, 0.08 to 0.87) but not for estrogen receptor-positive tumors (HR, 0.91; 95% CI, 0.45 to 1.84: P for heterogeneity = .09). CONCLUSION Postmenopausal patients with breast cancer who have high serum enterolactone levels may have better survival.
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Affiliation(s)
- Katharina Buck
- Unit of Genetic Epidemiology, Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
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Seo HS, Ju JH, Jang K, Shin I. Induction of apoptotic cell death by phytoestrogens by up-regulating the levels of phospho-p53 and p21 in normal and malignant estrogen receptor α-negative breast cells. Nutr Res 2011; 31:139-46. [PMID: 21419318 DOI: 10.1016/j.nutres.2011.01.011] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2010] [Revised: 01/06/2011] [Accepted: 01/24/2011] [Indexed: 01/10/2023]
Abstract
In this study, we investigated the underlying mechanism by which phytoestrogens suppress the growth of normal (MCF-10A) and malignant (MDA-MB-231) estrogen receptor α (ERα)-negative breast cells. We hypothesized that phytoestrogen inhibits the proliferation of ERα-negative breast cancer cells. We found that all tested phytoestrogens (genistein, apigenin, and quercetin) suppressed the growth of both MCF-10A and MDA-MB-231 cells, as revealed by proliferation assays. These results were accompanied by an increase in the sub-G0/G1 apoptotic fractions as well as an increase in the cell population in the G2/M phase in both cell types, as revealed by cell cycle analysis. When we assessed the effect of phytoestrogens on the level of intracellular signaling molecules by Western blot analysis, we found that phytoestrogens increased the level of active p53 (phospho-p53) without changing the p53 level in both MCF-10A and MDA-MB-231 cells. Phytoestrogens also induced an increase in p21, a p53 target gene, and a decrease in either Bcl-xL or cyclin B1 in both cell types. In contrast, the protein levels of phosphatase and tensin homolog, cyclin D1, cell division control protein 2 homolog, phospho-cell division control protein 2 homolog, and p27 were not changed after phytoestrogen treatment. Our data indicate that phytoestrogens induce apoptotic cell death of ERα-negative breast cancer cells via p53-dependent pathway and suggest that phytoestrogens may be promising agents in the treatment and prevention of ERα-negative breast cancer.
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Affiliation(s)
- Hye-Sook Seo
- Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, South Korea
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This P, de Cremoux P, Leclercq G, Jacquot Y. A critical view of the effects of phytoestrogens on hot flashes and breast cancer risk. Maturitas 2011; 70:222-6. [PMID: 21813250 DOI: 10.1016/j.maturitas.2011.07.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2011] [Revised: 06/07/2011] [Accepted: 07/03/2011] [Indexed: 01/26/2023]
Abstract
The increased risk of breast cancer recently observed with some specific estro-progestin associations has raised concerns about the harmful effects of menopausal hormone replacement therapy (HRT). It has been proposed that phytoestrogens (PEs), which have a similar chemical structure to estrogens, could be used as HRT. The main selling points of these preparations concern the management of hot flashes and their potential beneficial effects on breast tissue. In this review, we will address the effects of PE on hot flashes and breast cancer risk as well as the questions raised on a chemical point of view. We conclude that the efficacy of a PE rich diet or nutritional supplements is not clearly established. The use of PE as an alternative for HRT cannot be advocated for now, due to insufficient and conflicting data on efficacy and safety. Moreover, due to the hormone dependence of breast cancer, PE use must be contraindicated in breast cancer survivors.
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Affiliation(s)
- Pascale This
- Pole de Sénologie, Service d'Oncogénétique, Institut Curie, 26, rue d'Ulm, 75248 Paris Cedex 05, France.
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Zaineddin AK, Vrieling A, Buck K, Becker S, Linseisen J, Flesch-Janys D, Kaaks R, Chang-Claude J. Serum enterolactone and postmenopausal breast cancer risk by estrogen, progesterone and herceptin 2 receptor status. Int J Cancer 2011; 130:1401-10. [DOI: 10.1002/ijc.26157] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2011] [Accepted: 04/07/2011] [Indexed: 11/10/2022]
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McLaughlin JM, Olivo-Marston S, Vitolins MZ, Bittoni M, Reeves KW, Degraffinreid CR, Schwartz SJ, Clinton SK, Paskett ED. Effects of tomato- and soy-rich diets on the IGF-I hormonal network: a crossover study of postmenopausal women at high risk for breast cancer. Cancer Prev Res (Phila) 2011; 4:702-10. [PMID: 21430071 DOI: 10.1158/1940-6207.capr-10-0329] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
To determine whether dietary modifications with tomato products and/or a soy supplement affected circulating levels of insulin-like growth factor (IGF)-1 and other markers of cell signaling in postmenopausal women at risk for developing breast cancer. Eligible and consented postmenopausal women at high risk for developing breast cancer were enrolled in a 26-week, two-arm (tomato and soy, 10 weeks each) longitudinal dietary intervention study in which each woman served as her own control. Changes in biochemical endpoints including IGF-I, IGF-binding protein (IGFBP)-3, estradiol, sex hormone-binding globulin (SHBG), C-peptide, and insulin were measured for each intervention arm. Carotenoid and isoflavone levels were measured to assess adherence. Significant increases in carotenoid and isoflavone levels during the tomato and soy study arms, respectively, suggested that women were adherent to both arms of the intervention. The tomato-rich diet had little effect on cell-signaling biomarkers previously associated with breast cancer risk. However, results of the soy intervention showed that concentrations of IGF-I and IGFBP-3 increased by 21.6 and 154.7 μmol/L, respectively (P = 0.001 for both) and SHBG decreased by 5.4 μmol/L (P < 0.001) after consumption of the soy protein supplement. Increased soy protein intake may lead to small, but significant, increases in IGF-I and IGFBP-3. Soy consumption also led to a significant decrease in SHBG, which has been hypothesized to promote, rather than prevent, cancer growth. Previous epidemiologic studies, however, have confirmed protective effect of soy on breast cancer. Additional investigation about the effect of soy on breast cancer risk and its mechanism of action is warranted.
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Affiliation(s)
- John M McLaughlin
- The Ohio State University, Comprehensive Cancer Center, Columbus, OH 43210, USA.
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Caan BJ, Natarajan L, Parker B, Gold EB, Thomson C, Newman V, Rock CL, Pu M, Al-Delaimy W, Pierce JP. Soy food consumption and breast cancer prognosis. Cancer Epidemiol Biomarkers Prev 2011; 20:854-8. [PMID: 21357380 DOI: 10.1158/1055-9965.epi-10-1041] [Citation(s) in RCA: 65] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Contrary to earlier clinical studies suggesting that soy may promote breast tumor growth, two recent studies show that soy-containing foods are not adversely related to breast cancer prognosis. We examined, using data from the Women's Healthy Eating and Living (WHEL) study, the effect of soy intake on breast cancer prognosis. METHODS Three thousand eighty-eight breast cancer survivors, diagnosed between 1991 and 2000 with early-stage breast cancer and participating in WHEL, were followed for a median of 7.3 years. Isoflavone intakes were measured postdiagnosis by using a food frequency questionnaire. Women self-reported new outcome events semiannually, which were then verified by medical records and/or death certificates. HRs and 95% CIs representing the association between either a second breast cancer event or death and soy intake were computed, adjusting for study group and other covariates, using the delayed entry Cox proportional hazards model. RESULTS As isoflavone intake increased, risk of death decreased (P for trend = 0.02). Women at the highest levels of isoflavone intake (>16.3 mg isoflavones) had a nonsignificant 54% reduction in risk of death. CONCLUSION Our study is the third epidemiologic study to report no adverse effects of soy foods on breast cancer prognosis. IMPACT These studies, taken together, which vary in ethnic composition (two from the United States and one from China) and by level and type of soy consumption, provide the necessary epidemiologic evidence that clinicians no longer need to advise against soy consumption for women with a diagnosis of breast cancer.
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Affiliation(s)
- Bette J Caan
- Division of Research, Kasier Permanente, Oakland, CA 94612, USA.
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Update in women's health for the general internist. J Gen Intern Med 2011; 26:207-13. [PMID: 20824360 PMCID: PMC3019328 DOI: 10.1007/s11606-010-1503-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2010] [Revised: 08/02/2010] [Accepted: 08/18/2010] [Indexed: 11/01/2022]
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Significant changes in dietary intake and supplement use after breast cancer diagnosis in a UK multicentre study. Breast Cancer Res Treat 2011; 128:473-82. [DOI: 10.1007/s10549-010-1238-8] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2010] [Accepted: 10/20/2010] [Indexed: 10/18/2022]
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Leclercq G, de Cremoux P, This P, Jacquot Y. Lack of sufficient information on the specificity and selectivity of commercial phytoestrogens preparations for therapeutic purposes. Maturitas 2011; 68:56-64. [DOI: 10.1016/j.maturitas.2010.10.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2010] [Revised: 10/11/2010] [Accepted: 10/12/2010] [Indexed: 12/16/2022]
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Fink BN, Weiner JG, Jordan TR, Thompson AJ, Salvage TC, Coman M, Balls-Berry J. Early stage breast cancer and its association with diet and exercise-related perceptions and behaviors to prevent recurrence. BREAST CANCER-BASIC AND CLINICAL RESEARCH 2010; 4:65-72. [PMID: 21151861 PMCID: PMC2999512 DOI: 10.4137/bcbcr.s6265] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Background: The favorable prognosis for early stage breast cancer survivors may be a reason for the minimal research regarding their quality of life. Prior research has observed more long-term weight gain among early stage survivors compared to cancer-free women of a similar age. It would be useful to study survivors’ perceptions and reported behaviors regarding diet and exercise to see if there is a correlation with previous studies. Methods: A sample of 700 breast cancer survivors from Ohio and Michigan was randomly selected from the Northwest Ohio affiliate of the Susan G. Komen For the Cure mailing list and sent a survey for completion. Results: 389 survivors completed the survey and among Stage 1 (50/197 = 25.4%) and Stage 2 survivors (24/105 = 22.9%), a small proportion had a positive correlation between self-reported dietary behaviors and their perceived benefits of eating fruits and vegetables. Similar correlations were observed between their self-reported exercise behaviors and their perceived benefits of exercise (Stage 1: 36/197 = 18.3%, Stage 2: 18/105 = 17.1%). Conclusions: Regardless of stage, a small proportion of survivors’ self-reported dietary and exercise behaviors match their perceived benefits of diet and exercise. Factors such as access, motivation, and lack of co-morbidities among early stage survivors may prevent them from living healthier post-diagnosis. More thorough dietary and clinical measurements will provide greater certainty. Thus, innovative, sustainable programs must be accessible and provide motivation and social support from family, friends, and other survivors to truly improve quality of life.
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Affiliation(s)
- Brian N Fink
- Department of Public Health and Preventive Medicine, University of Toledo, Toledo, Ohio, USA
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Li XL, Zhou HB, Cheng WD, Meng XH, Zhang QJ, Wang LX. WITHDRAWN: Effect of phytoestrogen isoflavone on MPP(+)-induced apoptosis in PC12 cells. Biomed Pharmacother 2010:S0753-3322(10)00185-X. [PMID: 21115318 DOI: 10.1016/j.biopha.2010.09.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2010] [Accepted: 09/30/2010] [Indexed: 10/18/2022] Open
Abstract
The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.bionut.2010.09.004. The duplicate article has therefore been withdrawn.
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Affiliation(s)
- Xue-Li Li
- Department of Neurology, Liaocheng People's Hospital and Liaocheng Clinical School of Taishan Medical University, Liaocheng, Shandong, 252000, PR China
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Dumbrepatil AB, Lee SG, Chung SJ, Lee MG, Park BC, Kim TJ, Woo EJ. Development of a nanoparticle-based FRET sensor for ultrasensitive detection of phytoestrogen compounds. Analyst 2010; 135:2879-86. [PMID: 20877819 DOI: 10.1039/c0an00385a] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Phytoestrogens are plant compounds that mimic the actions of endogenous estrogens. The abundance of these chemicals in nature and their potential effects on health require the development of a convenient method to detect phytoestrogens. We have developed a nanoparticle (NP)-conjugated FRET probe based on the human estrogen receptor α (ER) ligand-binding domain (LBD) to detect phytoestrogens. The NP-conjugated FRET probe showed fluorescence signals for genistein, resveratrol and daidzein compounds with Δ ratios of 1.65, 2.60 and 1.37 respectively, which are approximately six times greater compared to individual FRET probes. A significantly higher signal for resveratrol versus genistein and daidzein indicates that the probe can differentiate between antagonistic phytoalexin substances and agonistic isoflavone compounds. NP-conjugated probes demonstrated a wide dynamic range, ranging from 10(-18) to 10(-1) M with EC(50) values of 9.6 × 10(-10), 9.0 × 10(-10) and 9.2 × 10(-10) M for genistein, daidzein and resveratrol respectively, whereas individual probes detected concentrations of 10(-13) to 10(-4) M for phytoestrogens compounds. The time profile revealed that the NP-conjugated probe is stable over 30 h and there is not a significant deviation in the FRET signal at room temperature. These data demonstrate that conjugation of a FRET probe to nanoparticles is able to serve as an effective FRET sensor for monitoring bioactive compounds with significantly increased sensitivity, dynamic range and stability.
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Affiliation(s)
- Arti B Dumbrepatil
- Korea Research Institute of Biosciences and Biotechnology (KRIBB), 111 Gwahangno, Yuseong-gu, Daejeon, 305-806, Korea
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Abstract
The increased interest in phytoestrogens in the management of menopausal symptoms followed the publication of the Women's Health Initiative study. A wide-spread perception that these plant-derived compounds are equivalent to estrogen was established. These compounds evolved to fulfill the needs of plant physiological processes and are natural for the plant cells but not natural to the human cell. Epidemiological data suggest a possible protective effect of phytoestrogen if consumed during adolescence, but later on in life this effect is not clear. The utility of phytoestrogen as a "natural and safe" alternative to estrogen in alleviating vasomotor symptoms has failed the test in randomized clinical trials. Because many breast cancer sufferers seek in phytoestrogen a relief of estrogen deficiency symptoms, the possible interaction of such remedies with risk of recurrence of breast cancer or interference with tamoxifen action should not be overlooked.
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Lehraiki A, Attoumbré J, Bienaimé C, Matifat F, Bensaddek L, Nava-Saucedo E, Fliniaux MA, Ouadid-Ahidouch H, Baltora-Rosset S. Extraction of Lignans from Flaxseed and Evaluation of Their Biological Effects on Breast Cancer MCF-7 and MDA-MB-231 Cell Lines. J Med Food 2010; 13:834-41. [DOI: 10.1089/jmf.2009.0172] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Affiliation(s)
- Abdelali Lehraiki
- Biology of Plantes and Insects, EA 3900, Faculty of Pharmacy, University of Picardie Jules Verne, Amiens, France
- Laboratory of Cellular and Molecular Physiology, JE 2530, Faculty of Sciences, University of Picardie Jules Verne, Amiens, France
| | - Jacques Attoumbré
- Biology of Plantes and Insects, EA 3900, Faculty of Pharmacy, University of Picardie Jules Verne, Amiens, France
| | - Christophe Bienaimé
- Biology of Plantes and Insects, EA 3900, Faculty of Pharmacy, University of Picardie Jules Verne, Amiens, France
| | - Fabrice Matifat
- Laboratory of Cellular and Molecular Physiology, JE 2530, Faculty of Sciences, University of Picardie Jules Verne, Amiens, France
| | - Lamine Bensaddek
- Biology of Plantes and Insects, EA 3900, Faculty of Pharmacy, University of Picardie Jules Verne, Amiens, France
| | - Edmundo Nava-Saucedo
- Biology of Plantes and Insects, EA 3900, Faculty of Pharmacy, University of Picardie Jules Verne, Amiens, France
| | - Marc-André Fliniaux
- Biology of Plantes and Insects, EA 3900, Faculty of Pharmacy, University of Picardie Jules Verne, Amiens, France
| | - Halima Ouadid-Ahidouch
- Laboratory of Cellular and Molecular Physiology, JE 2530, Faculty of Sciences, University of Picardie Jules Verne, Amiens, France
| | - Sylvie Baltora-Rosset
- Biology of Plantes and Insects, EA 3900, Faculty of Pharmacy, University of Picardie Jules Verne, Amiens, France
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Al-Maharik N, Botting NP. A versatile synthesis of [2,3,4-13C3]isoflavones. J Labelled Comp Radiopharm 2010. [DOI: 10.1002/jlcr.1732] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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Nagata C. Factors to consider in the association between soy isoflavone intake and breast cancer risk. J Epidemiol 2010; 20:83-9. [PMID: 20173308 PMCID: PMC3900805 DOI: 10.2188/jea.je20090181] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
It has been suggested that soy isoflavones have protective effects against breast cancer. However, data from epidemiological studies are not conclusive. A recent meta-analysis showed that soy intake was inversely associated with breast cancer risk in Asian but not Western populations, which indicates that protection against breast cancer may require that women consume levels of soy typical in Asian diets. In addition to the amount of soy isoflavones consumed, the form and food source of isoflavones, timing of isoflavone exposure, estrogen receptor status of tumors, and equol-producer status and hormonal profile of individuals may modify the association between soy isoflavone intake and the risk of breast cancer. These factors might explain the heterogeneity of results from studies. This present report contrasts background data from Japanese and Western women to identify the potential modifying of these factors.
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Affiliation(s)
- Chisato Nagata
- Department of Epidemiology & Preventive Medicine, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
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