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Cavalleri Sousa T, de Oliveira CB, Silva Ricardo ML, Musa de Aquino A, Scarano WR, Cruz Veras AS, Almeida Tavares ME, Teixeira GR, Castillho ACD, Pacagnelli FL, Zalotti Brandt J, de Oliveira Mendes L. Prostate histological investigation in rats exposed to bisphenol a and phytochemicals during the perinatal period and subjected to hormonal stimulus in adulthood. INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2024; 34:201-212. [PMID: 36319067 DOI: 10.1080/09603123.2022.2140127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 10/21/2022] [Indexed: 06/16/2023]
Abstract
Bisphenol A (BPA) is an environmentally dispersed chemical associated with tumor development. Phytochemicals such as indole-3-carbinol (I3C) and genistein (GEN) have chemoprotective effects on tumor cells. Thus, this study aimed to evaluate the prostatic morphological aspects of rats exposed to BPA, GEN, and I3C during the perinatal period and submitted to hormonal stimulus in adulthood. Blood was collected to obtain hormone concentrations. Slides stained with hematoxylin & eosin, and picrosirius were subjected to fractal, stereological, morphometric, and collagen quantification analysis. I3C decreased the plasma dihydrotestosterone levels, and both phytochemicals increased the plasma estrogen levels. Unlike phytochemicals, BPA did not alter any of the parameters evaluated. GEN reduced the epithelial height, while I3C increased the fractal dimension and stromal collagen. Although BPA did not alter the prostate morphology, the phytochemicals provided beneficial effects for the prostate histological organization in adult animals subjected to hormonal stimulus.
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Affiliation(s)
- Thainá Cavalleri Sousa
- Graduate Program in Animal Science, Western São Paulo University (UNOESTE), Presidente Prudente, Brazil
| | | | - Maria Luiza Silva Ricardo
- Graduate Program in Animal Science, Western São Paulo University (UNOESTE), Presidente Prudente, Brazil
| | | | | | - Allice Santos Cruz Veras
- Experimental Laboratory of Exercise Biology (LEBioEx), São Paulo State University (UNESP), Presidente Prudente, Brazil
| | - Maria Eduarda Almeida Tavares
- Experimental Laboratory of Exercise Biology (LEBioEx), São Paulo State University (UNESP), Presidente Prudente, Brazil
| | - Giovana Rampazzo Teixeira
- Experimental Laboratory of Exercise Biology (LEBioEx), São Paulo State University (UNESP), Presidente Prudente, Brazil
| | | | - Francis Lopes Pacagnelli
- Graduate Program in Animal Science, Western São Paulo University (UNOESTE), Presidente Prudente, Brazil
| | | | - Leonardo de Oliveira Mendes
- Graduate Program in Animal Science, Western São Paulo University (UNOESTE), Presidente Prudente, Brazil
- Master Program in Health Science, Western São Paulo University (UNOESTE), Presidente Prudente, Brazil
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Optimization and validation of analytical RP-HPLC methods for the quantification of glucosinolates and isothiocyanates in Nasturtium officinale R. Br and Brassica oleracea. Lebensm Wiss Technol 2022. [DOI: 10.1016/j.lwt.2022.113668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Liu Z, Wang H, Lv J, Luo S, Hu L, Wang J, Li L, Zhang G, Xie J, Yu J. Effects of Plant Hormones, Metal Ions, Salinity, Sugar, and Chemicals Pollution on Glucosinolate Biosynthesis in Cruciferous Plant. FRONTIERS IN PLANT SCIENCE 2022; 13:856442. [PMID: 35574082 PMCID: PMC9096887 DOI: 10.3389/fpls.2022.856442] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 03/17/2022] [Indexed: 06/15/2023]
Abstract
Cruciferous vegetable crops are grown widely around the world, which supply a multitude of health-related micronutrients, phytochemicals, and antioxidant compounds. Glucosinolates (GSLs) are specialized metabolites found widely in cruciferous vegetables, which are not only related to flavor formation but also have anti-cancer, disease-resistance, and insect-resistance properties. The content and components of GSLs in the Cruciferae are not only related to genotypes and environmental factors but also are influenced by hormones, plant growth regulators, and mineral elements. This review discusses the effects of different exogenous substances on the GSL content and composition, and analyzes the molecular mechanism by which these substances regulate the biosynthesis of GSLs. Based on the current research status, future research directions are also proposed.
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Affiliation(s)
- Zeci Liu
- College of Horticulture, Gansu Agricultural University, Lanzhou, China
| | - Huiping Wang
- College of Horticulture, Gansu Agricultural University, Lanzhou, China
| | - Jian Lv
- College of Horticulture, Gansu Agricultural University, Lanzhou, China
| | - Shilei Luo
- College of Horticulture, Gansu Agricultural University, Lanzhou, China
| | - Linli Hu
- College of Horticulture, Gansu Agricultural University, Lanzhou, China
| | - Jie Wang
- College of Horticulture, Gansu Agricultural University, Lanzhou, China
| | - Lushan Li
- College of Horticulture, Gansu Agricultural University, Lanzhou, China
| | - Guobin Zhang
- College of Horticulture, Gansu Agricultural University, Lanzhou, China
| | - Jianming Xie
- College of Horticulture, Gansu Agricultural University, Lanzhou, China
| | - Jihua Yu
- College of Horticulture, Gansu Agricultural University, Lanzhou, China
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Torres-Contreras AM, Nair V, Senés-Guerrero C, Pacheco A, González-Agüero M, Ramos-Parra PA, Cisneros-Zevallos L, Jacobo-Velázquez DA. Chemical Genetics Applied to Elucidate the Physiological Role of Stress-Signaling Molecules on the Wound-Induced Accumulation of Glucosinolates in Broccoli. PLANTS (BASEL, SWITZERLAND) 2021; 10:plants10122660. [PMID: 34961133 PMCID: PMC8706940 DOI: 10.3390/plants10122660] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 11/28/2021] [Accepted: 12/01/2021] [Indexed: 05/17/2023]
Abstract
Wounding stress is an effective strategy to induce glucosinolate (GS) biosynthesis in broccoli. However, there is insufficient knowledge on the physiological and molecular mechanisms underlying this stress response. Herein, a chemical-genetic approach was applied to elucidate the role of jasmonic acid (JA), ethylene (ET), and reactive oxygen species (ROS) on the wound-induced biosynthesis of GS. Broccoli was processed into chops to induce wounding stress. Broccoli chops were treated with phenidone (PHEN) and diphenyleneiodonium chloride (DPI) as inhibitors of JA and ROS biosynthesis, respectively, whereas 1-methylcyclopropene (1-MCP) was applied as an inhibitor of ET action. Wounding stress induced the expression of genes related to the biosynthesis of indolic and aliphatic GS, which was correlated with the accumulation of GS and modulated by the inhibitors of signaling molecules applied. Results of gene expression analysis indicated that JA played a key role in the activation of most genes, followed by ROS. Furthermore, except for the CYP79B2 gene, PHEN and 1-MCP synergistically downregulated the expression of GS biosynthetic genes evaluated, showing that the interaction between JA and ET was fundamental to modulate GS biosynthesis. Results presented herein increased our knowledge of the physiological and molecular mechanisms governing the wound-induced biosynthesis of GS in broccoli.
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Affiliation(s)
- Ana M. Torres-Contreras
- Tecnologico de Monterrey, Escuela de Ingeniería y Ciencias, Av. Eugenio Garza Sada 2501, Monterrey C.P. 64849, Nuevo Leon, Mexico; (A.M.T.-C.); (A.P.); (P.A.R.-P.)
| | - Vimal Nair
- Department of Horticultural Sciences, Texas A&M University, College Station, TX 77843, USA; (V.N.); (L.C.-Z.)
| | - Carolina Senés-Guerrero
- Tecnologico de Monterrey, Escuela de Ingeniería y Ciencias, Av. General Ramón Corona 2514, Zapopan C.P. 45201, Jalisco, Mexico;
| | - Adriana Pacheco
- Tecnologico de Monterrey, Escuela de Ingeniería y Ciencias, Av. Eugenio Garza Sada 2501, Monterrey C.P. 64849, Nuevo Leon, Mexico; (A.M.T.-C.); (A.P.); (P.A.R.-P.)
| | - Mauricio González-Agüero
- Postharvest Unit, Institute for Agricultural Research, INIA-La Platina, Santa Rosa, Santiago 11610, Chile;
| | - Perla A. Ramos-Parra
- Tecnologico de Monterrey, Escuela de Ingeniería y Ciencias, Av. Eugenio Garza Sada 2501, Monterrey C.P. 64849, Nuevo Leon, Mexico; (A.M.T.-C.); (A.P.); (P.A.R.-P.)
| | - Luis Cisneros-Zevallos
- Department of Horticultural Sciences, Texas A&M University, College Station, TX 77843, USA; (V.N.); (L.C.-Z.)
| | - Daniel A. Jacobo-Velázquez
- Tecnologico de Monterrey, Escuela de Ingeniería y Ciencias, Av. General Ramón Corona 2514, Zapopan C.P. 45201, Jalisco, Mexico;
- Correspondence: ; Tel.: +52-312-119-1650
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Guan Y, Hu W, Xu Y, Sarengaowa, Ji Y, Yang X, Feng K. Proteomic analysis validates previous findings on wounding-responsive plant hormone signaling and primary metabolism contributing to the biosynthesis of secondary metabolites based on metabolomic analysis in harvested broccoli (Brassica oleracea L. var. italica). Food Res Int 2021; 145:110388. [PMID: 34112391 DOI: 10.1016/j.foodres.2021.110388] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Revised: 04/08/2021] [Accepted: 05/02/2021] [Indexed: 10/21/2022]
Abstract
The plant wound-response is a complex process that generates physiological modifications for protecting the wounded tissue. In this study, tandem mass tag (TMT)-based quantitative proteomic analysis was performed to clarify the comprehensive molecular mechanism for the wound-response of broccoli subjected to two wounding intensities (0.04 and 1.85 m2 kg-1 for florets and shreds, respectively). Furthermore, integrated proteomic and metabolomic analysis was performed to reveal the interaction among the critical metabolic pathway responses to wounding. The results show that a total of 399 proteins and 266 proteins were identified as differentially expressed proteins (DEPs) in florets and shreds broccoli compared to control, respectively. Furthermore, 167 DEPs were detected in shreds broccoli compared to the florets broccoli. Salicylic acid (SA) and ethylene (ET) biosynthesis were more susceptible to being induced by wounding with lower intensities, whereas, phenylpropanoid biosynthesis, aliphatic glucosinolate synthesis and jasmonic acid (JA) biosynthesis were more susceptible to being activated by wounding with higher intensities. The activation of starch and sucrose metabolism, TCA cycle, glycolysis, pentose phosphate could provide carbon sources and ATP for the production of amino acids including phenylalanine, valine, threonine, isoleucine, L-methionine, methionine and histidine. The motivation of carbohydrate metabolic pathways and amino acid biosynthesis-related pathways promotes the precursor levels for phenolic substances and glucosinolate synthesis. Furthermore, the accumulation of SA, ET and JA may activated secondary metabolite biosynthesis through the regulation of critical proteins involved in the corresponding metabolic pathways.
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Affiliation(s)
- Yuge Guan
- School of Bioengineering, Dalian University of Technology, Dalian 116024, China
| | - Wenzhong Hu
- College of Life Science, Dalian Minzu University, Dalian 116600, China; Key Laboratory of Biotechnology and Bioesources Utilization, Ministry of Education, Dalian 116600, China.
| | - Yongping Xu
- School of Bioengineering, Dalian University of Technology, Dalian 116024, China
| | - Sarengaowa
- School of Bioengineering, Dalian University of Technology, Dalian 116024, China
| | - Yaru Ji
- School of Bioengineering, Dalian University of Technology, Dalian 116024, China
| | - Xiaozhe Yang
- School of Bioengineering, Dalian University of Technology, Dalian 116024, China
| | - Ke Feng
- College of Life Science, Dalian Minzu University, Dalian 116600, China; Key Laboratory of Biotechnology and Bioesources Utilization, Ministry of Education, Dalian 116600, China
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Cardoso HJ, Carvalho TMA, Fonseca LRS, Figueira MI, Vaz CV, Socorro S. Revisiting prostate cancer metabolism: From metabolites to disease and therapy. Med Res Rev 2020; 41:1499-1538. [PMID: 33274768 DOI: 10.1002/med.21766] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 10/24/2020] [Accepted: 11/22/2020] [Indexed: 12/24/2022]
Abstract
Prostate cancer (PCa), one of the most commonly diagnosed cancers worldwide, still presents important unmet clinical needs concerning treatment. In the last years, the metabolic reprogramming and the specificities of tumor cells emerged as an exciting field for cancer therapy. The unique features of PCa cells metabolism, and the activation of specific metabolic pathways, propelled the use of metabolic inhibitors for treatment. The present work revises the knowledge of PCa metabolism and the metabolic alterations that underlie the development and progression of the disease. A focus is given to the role of bioenergetic sources, namely, glucose, lipids, and glutamine sustaining PCa cell survival and growth. Moreover, it is described as the action of oncogenes/tumor suppressors and sex steroid hormones in the metabolic reprogramming of PCa. Finally, the status of PCa treatment based on the inhibition of metabolic pathways is presented. Globally, this review updates the landscape of PCa metabolism, highlighting the critical metabolic alterations that could have a clinical and therapeutic interest.
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Affiliation(s)
- Henrique J Cardoso
- CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal
| | - Tiago M A Carvalho
- CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal
| | - Lara R S Fonseca
- CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal
| | - Marília I Figueira
- CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal
| | - Cátia V Vaz
- CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal
| | - Sílvia Socorro
- CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal
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Maina S, Misinzo G, Bakari G, Kim HY. Human, Animal and Plant Health Benefits of Glucosinolates and Strategies for Enhanced Bioactivity: A Systematic Review. Molecules 2020; 25:E3682. [PMID: 32806771 PMCID: PMC7464879 DOI: 10.3390/molecules25163682] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 08/08/2020] [Accepted: 08/10/2020] [Indexed: 12/14/2022] Open
Abstract
Glucosinolates (GSs) are common anionic plant secondary metabolites in the order Brassicales. Together with glucosinolate hydrolysis products (GSHPs), they have recently gained much attention due to their biological activities and mechanisms of action. We review herein the health benefits of GSs/GSHPs, approaches to improve the plant contents, their bioavailability and bioactivity. In this review, only literature published between 2010 and March 2020 was retrieved from various scientific databases. Findings indicate that these compounds (natural, pure, synthetic, and derivatives) play an important role in human/animal health (disease therapy and prevention), plant health (defense chemicals, biofumigants/biocides), and food industries (preservatives). Overall, much interest is focused on in vitro studies as anti-cancer and antimicrobial agents. GS/GSHP levels improvement in plants utilizes mostly biotic/abiotic stresses and short periods of phytohormone application. Their availability and bioactivity are directly proportional to their contents at the source, which is affected by methods of food preparation, processing, and extraction. This review concludes that, to a greater extent, there is a need to explore and improve GS-rich sources, which should be emphasized to obtain natural bioactive compounds/active ingredients that can be included among synthetic and commercial products for use in maintaining and promoting health. Furthermore, the development of advanced research on compounds pharmacokinetics, their molecular mode of action, genetics based on biosynthesis, their uses in promoting the health of living organisms is highlighted.
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Affiliation(s)
- Sylvia Maina
- Smart Farm Research Center, Korea Institute of Science and Technology (KIST), Gangneung, Gangwon 25451, Korea;
- College of Veterinary Medicine and Biomedical Sciences, Sokoine University of Agriculture, Morogoro 25523, Tanzania; (G.M.); (G.B.)
- SACIDS Africa Centre of Excellence for Infectious Diseases, Sokoine University of Agriculture, Morogoro 25523, Tanzania
| | - Gerald Misinzo
- College of Veterinary Medicine and Biomedical Sciences, Sokoine University of Agriculture, Morogoro 25523, Tanzania; (G.M.); (G.B.)
- SACIDS Africa Centre of Excellence for Infectious Diseases, Sokoine University of Agriculture, Morogoro 25523, Tanzania
| | - Gaymary Bakari
- College of Veterinary Medicine and Biomedical Sciences, Sokoine University of Agriculture, Morogoro 25523, Tanzania; (G.M.); (G.B.)
| | - Ho-Youn Kim
- Smart Farm Research Center, Korea Institute of Science and Technology (KIST), Gangneung, Gangwon 25451, Korea;
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Garcia-Ibañez P, Moreno DA, Nuñez-Gomez V, Agudelo A, Carvajal M. Use of elicitation in the cultivation of Bimi® for food and ingredients. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2020; 100:2099-2109. [PMID: 31875967 DOI: 10.1002/jsfa.10233] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Revised: 12/19/2019] [Accepted: 12/26/2019] [Indexed: 06/10/2023]
Abstract
BACKGROUND Cruciferous foods rich in health-promoting metabolites are of particular interest to consumers as well as being a good source of bioactives-enriched ingredients. Several elicitors have been used to stimulate the biosynthesis and accumulation of secondary metabolites in foods; however, little is known about the response of new hybrid varieties, such as Bimi®, under field-crop production conditions. Therefore, this study was designed to evaluate the effect of salicylic acid (200 μmol L-1 , SA), methyl jasmonate (100 μmol L-1 , MeJA), and their combination on Bimi plant organs (inflorescences and aerial vegetative tissues - stems and leaves). For this, the composition of the glucosinolates present in the tissues was evaluated. Also, aqueous extracts of the plant material, obtained with different times of extraction with boiling water, were studied. RESULTS The results indicate that the combined treatment (SA + MeJA) significantly increased the content of glucosinolates in the inflorescences and that MeJA was the most effective elicitor in leaves. Regarding the aqueous extracts, the greatest amount of glucosinolates was extracted at 30 min - except for the leaves elicited with MeJA, for which 15 min was optimal. CONCLUSION The elicitation in the field enriched leaves in glucobrassicin (GB), 4-methoxyglucobrassicin (MGB), and neoglucobrassicin (NGB) and stems and inflorescences in glucoraphanin, 4-hydroxyglucobrassicin, GB, MGB, and NGB. In this way, this enhanced vegetable material favored the presence of bioactives in the extracts, which is of great interest regarding enriched foods and ingredients with added value obtained from them. © 2019 Society of Chemical Industry.
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Affiliation(s)
- Paula Garcia-Ibañez
- Aquaporins Group, Department of Plant Nutrition, CEBAS-CSIC, Murcia, Spain
- Phytochemistry and Healthy Foods Lab, Department of Food Science Technology, CEBAS-CSIC, Murcia, Spain
| | - Diego A Moreno
- Phytochemistry and Healthy Foods Lab, Department of Food Science Technology, CEBAS-CSIC, Murcia, Spain
| | - Vanessa Nuñez-Gomez
- Phytochemistry and Healthy Foods Lab, Department of Food Science Technology, CEBAS-CSIC, Murcia, Spain
| | - Agatha Agudelo
- R&D Special Collaborative Projects, Sakata Seed Ibérica S.L.U., Valencia, Spain
- IBMCP, Universidad Politécnica de Valencia, Valencia, Spain
| | - Micaela Carvajal
- Aquaporins Group, Department of Plant Nutrition, CEBAS-CSIC, Murcia, Spain
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Aguilar-Camacho M, Welti-Chanes J, Jacobo-Velázquez DA. Combined effect of ultrasound treatment and exogenous phytohormones on the accumulation of bioactive compounds in broccoli florets. ULTRASONICS SONOCHEMISTRY 2019; 50:289-301. [PMID: 30274889 DOI: 10.1016/j.ultsonch.2018.09.031] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Revised: 09/17/2018] [Accepted: 09/21/2018] [Indexed: 05/23/2023]
Abstract
Postharvest treatments such as wounding, ultrasound (US) and the exogenous application of ethylene (ET) and methyl jasmonate (MJ) have been studied as an effective tool to improve the content of secondary metabolites in fresh produce. The present study evaluated the immediate and late response (storage for 72 h at 15 °C) to US treatment (20 min, frequency 24 kHz, amplitude 100 μm) alone and combined with exogenous MJ (250 ppm) and/or ET (1000 ppm) on glucosinolates, isothiocyanates, phenolic compounds and ascorbic acid content in broccoli florets. US treatment increased the extractability of glucosinolates [glucoraphanin (795%), 4-hydroxy glucobrassicin (153%), glucobrassicin (78.6%)] and phenolics [1-sinapoyl-2-feruloylgentiobiose (57.23%)] as compared with the control (CT). The combined application of MJ and US in broccoli florets, induced a synergistic effect on the accumulation of 4-hydroxy glucobrassicin (187.1%), glucoerucin (111.92%), gluconasturtiin (755.9%), neoglucobrassicin (232.8%), 3-O-caffeoylquinic acid (73.4%), 1-sinapoyl-2-ferulolylgentiobiose (56.0%), and 1,2,2-trisinapoylgentiobiose (136.7%) at 72 h of storage. Interestingly, when the three stressors were applied together the synergistic effect of US + MJ observed on the accumulation of glucosinolates and phenolics was repressed. In general, the ascorbic acid content was not affected by US treatment and decreased in most samples during storage. However, when MJ + ET were applied, the content of total ascorbic acid was significantly reduced in CT + MJ + ET and US + MJ + ET samples after 72 h of storage by 53.4% and 86.6%, respectively, as compared with CT 0 h samples. Based on the results herein obtained, the application of US can be an effective tool to enhance the extractability of certain glucocosinolate and phenolic compounds in broccoli. Moreover, due to the synergistic effect observed on the accumulation of bioactive compounds, the combined application of US and MJ could be a practical approach to yield higher levels of glucosinolates and phenolic compounds in broccoli during storage.
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Affiliation(s)
- Miguel Aguilar-Camacho
- Tecnologico de Monterrey, Escuela de Ingenieria y Ciencias, Av. Eugenio Garza Sada 2501 Sur, C.P. 64849 Monterrey, N.L., Mexico
| | - Jorge Welti-Chanes
- Tecnologico de Monterrey, Escuela de Ingenieria y Ciencias, Av. Eugenio Garza Sada 2501 Sur, C.P. 64849 Monterrey, N.L., Mexico
| | - Daniel A Jacobo-Velázquez
- Tecnologico de Monterrey, Escuela de Ingenieria y Ciencias, Av. Eugenio Garza Sada 2501 Sur, C.P. 64849 Monterrey, N.L., Mexico; Tecnologico de Monterrey, Escuela de Ingenieria y Ciencias, Av. General Ramón Corona 2514, Nuevo Mexico, C.P. 45138 Zapopan, Jal., Mexico.
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Grainger EM, Moran NE, Francis DM, Schwartz SJ, Wan L, Thomas-Ahner J, Kopec RE, Riedl KM, Young GS, Abaza R, Bahnson RR, Clinton SK. A Novel Tomato-Soy Juice Induces a Dose-Response Increase in Urinary and Plasma Phytochemical Biomarkers in Men with Prostate Cancer. J Nutr 2019; 149:26-35. [PMID: 30476157 PMCID: PMC6351139 DOI: 10.1093/jn/nxy232] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Accepted: 08/22/2018] [Indexed: 12/20/2022] Open
Abstract
Background Tomato and soy intake is associated with reduced prostate cancer risk or severity in epidemiologic and experimental studies. Objective On the basis of the principle that multiple bioactives in tomato and soy may act on diverse anticancer pathways, we developed and characterized a tomato-soy juice for clinical trials. In this phase 2 dose-escalating study, we examined plasma, prostate, and urine biomarkers of carotenoid and isoflavone exposure. Methods Men scheduled for prostatectomy were recruited to consume 0, 1, or 2 cans of tomato-soy juice/d before surgery (mean ± SD duration: 24 ± 4.6 d). The juice provided 20.6 mg lycopene and 66 mg isoflavone aglycone equivalents/177-mL can. Plasma carotenoids and urinary isoflavone metabolites were quantified by HPLC-photometric diode array and prostate carotenoids and isoflavones by HPLC-tandem mass spectrometry. Results We documented significant dose-response increases (P < 0.05) in plasma concentrations of tomato carotenoids. Plasma concentrations were 1.86-, 1.69-, 1.73-, and 1.69-fold higher for lycopene, β-carotene, phytoene, and phytofluene, respectively, for the 1-can/d group and 2.34-, 3.43-, 2.54-, and 2.29-fold higher, respectively, for the 2-cans/d group compared with 0 cans/d. Urinary isoflavones daidzein, genistein, and glycitein increased in a dose-dependent manner. Prostate carotenoid and isoflavone concentrations were not dose-dependent in this short intervention; yet, correlations between plasma carotenoid and urinary isoflavones with respective prostate concentrations were documented (R2 = 0.78 for lycopene, P < 0.001; R2 = 0.59 for dihydrodaidzein, P < 0.001). Secondary clustering analyses showed urinary isoflavone metabolite phenotypes. To our knowledge, this is the first demonstration of the phytoene and phytofluene in prostate tissue after a dietary intervention. Secondary analysis showed that the 2-cans/d group experienced a nonsignificant decrease in prostate-specific antigen slope compared with 0 cans/d (P = 0.078). Conclusion These findings provide the foundation for evaluating a well-characterized tomato-soy juice in human clinical trials to define the impact on human prostate carcinogenesis. This trial is registered at clinicaltrials.gov as NCT01009736.
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Affiliation(s)
- Elizabeth M Grainger
- The Ohio State University Comprehensive Cancer Center College of Medicine, The Ohio State University, Columbus, OH 43210
| | - Nancy E Moran
- The Ohio State University Comprehensive Cancer Center College of Medicine, The Ohio State University, Columbus, OH 43210,USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030
| | - David M Francis
- Department of Horticulture and Crop Science, The Ohio State University, Ohio Agricultural Research and Development Center, Wooster, OH 44691
| | - Steven J Schwartz
- Department of Food Science and Technology, College of Food, Agriculture, and Environmental Sciences, The Ohio State University, Columbus, OH 43210
| | - Lei Wan
- The Ohio State University Comprehensive Cancer Center College of Medicine, The Ohio State University, Columbus, OH 43210
| | - Jennifer Thomas-Ahner
- The Ohio State University Comprehensive Cancer Center College of Medicine, The Ohio State University, Columbus, OH 43210
| | - Rachel E Kopec
- Department of Food Science and Technology, College of Food, Agriculture, and Environmental Sciences, The Ohio State University, Columbus, OH 43210
| | - Ken M Riedl
- The Ohio State University Comprehensive Cancer Center College of Medicine, The Ohio State University, Columbus, OH 43210,Department of Food Science and Technology, College of Food, Agriculture, and Environmental Sciences, The Ohio State University, Columbus, OH 43210
| | - Gregory S Young
- The Ohio State University Comprehensive Cancer Center College of Medicine, The Ohio State University, Columbus, OH 43210,Center for Biostatistics College of Medicine, The Ohio State University, Columbus, OH 43210
| | - Ronney Abaza
- Department of Urology College of Medicine, The Ohio State University, Columbus, OH 43210
| | - Robert R Bahnson
- Department of Urology College of Medicine, The Ohio State University, Columbus, OH 43210
| | - Steven K Clinton
- The Ohio State University Comprehensive Cancer Center College of Medicine, The Ohio State University, Columbus, OH 43210,Division of Medical Oncology, College of Medicine The Ohio State University, Columbus, OH 43210,Address correspondence to SKC (e-mail: )
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Sulforaphane as anticancer agent: A double-edged sword? Tricky balance between effects on tumor cells and immune cells. Adv Biol Regul 2018; 71:79-87. [PMID: 30528536 DOI: 10.1016/j.jbior.2018.11.006] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Revised: 11/20/2018] [Accepted: 11/20/2018] [Indexed: 12/19/2022]
Abstract
Sulforaphane (SFN) is a naturally occurring isothiocyanate derived from cruciferous vegetables such as broccoli. It has been reported to inhibit the growth of a variety of cancers, such as breast, prostate, colon, skin, lung, gastric or bladder cancer. SFN is supposed to act primarily as an antioxidant due to the activation of the Nrf2-Keap1 signaling pathway. This enhances the activity of phase II detoxifying enzymes and the trapping of free radicals. Finally, SFN induces cell cycle arrest or apoptosis of tumor cells. Here, we discuss effects of SFN on the immune defense system. In contrast to the situation in tumor cells, SFN acts pro-oxidatively in primary human T cells. It increases intracellular ROS levels and decreases GSH, resulting in inhibition of T cell activation and T cell effector functions. Regarding the use of SFN as an "anticancer agent" we conclude that SFN could act as a double-edged sword. On the one hand it reduces carcinogenesis, on the other hand it blocks the T cell-mediated immune response, the latter being important for immune surveillance of tumors. Thus, SFN could also interfere with the successful application of immunotherapy by immune checkpoint inhibitors (e.g. CTLA-4 antibodies and PD-1/PD-L1 antibodies) or CAR T cells. Therefore, a combination of SFN with T cell-mediated cancer immunotherapies does not seem advisable.
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12
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Beaver LM, Lӧhr CV, Clarke JD, Glasser ST, Watson GW, Wong CP, Zhang Z, Williams DE, Dashwood RH, Shannon J, Thuillier P, Ho E. Broccoli Sprouts Delay Prostate Cancer Formation and Decrease Prostate Cancer Severity with a Concurrent Decrease in HDAC3 Protein Expression in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) Mice. Curr Dev Nutr 2018; 2:nzy002. [PMID: 30019025 PMCID: PMC6041877 DOI: 10.1093/cdn/nzy002] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2017] [Revised: 12/21/2017] [Accepted: 12/21/2017] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Cruciferous vegetables have been associated with the chemoprevention of cancer. Epigenetic regulators have been identified as important targets for prostate cancer chemoprevention. Treatment of human prostate cancer cells with sulforaphane (SFN), a chemical from broccoli and broccoli sprouts, inhibits epigenetic regulators such as histone deacetylase (HDAC) enzymes, but it is not known whether consumption of a diet high in broccoli sprouts impacts epigenetic mechanisms in an in vivo model of prostate cancer. OBJECTIVE In the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, we tested the hypothesis that a broccoli sprout diet suppresses prostate cancer, inhibits HDAC expression, alters histone modifications, and changes the expression of genes regulated by HDACs. METHODS TRAMP mice were fed a 15% broccoli sprout or control AIN93G diet; tissue samples were collected at 12 and 28 wk of age. RESULTS Mice fed broccoli sprouts had detectable amounts of SFN metabolites in liver, kidney, colon, and prostate tissues. Broccoli sprouts reduced prostate cancer incidence and progression to invasive cancer by 11- and 2.4-fold at 12 and 28 wk of age, respectively. There was a significant decline in HDAC3 protein expression in the epithelial cells of prostate ventral and anterior lobes at age 12 wk. Broccoli sprout consumption also decreased histone H3 lysine 9 trimethylation in the ventral lobe (age 12 wk), and decreased histone H3 lysine 18 acetylation in all prostate lobes (age 28 wk). A decline in p16 mRNA levels, a gene regulated by HDAC3, was associated with broccoli sprout consumption, but no significant changes were noted at the protein level. CONCLUSIONS Broccoli sprout intake was associated with a decline in prostate cancer occurrence and HDAC3 protein expression in the prostate, extending prior work that implicated loss of HDAC3/ corepressor interactions as a key preventive mechanism by SFN in vivo.
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Affiliation(s)
- Laura M Beaver
- School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR
- Linus Pauling Institute, Oregon State University, Corvallis, OR
| | - Christiane V Lӧhr
- Linus Pauling Institute, Oregon State University, Corvallis, OR
- Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR
| | - John D Clarke
- School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR
- Linus Pauling Institute, Oregon State University, Corvallis, OR
| | - Sarah T Glasser
- School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR
| | - Greg W Watson
- School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR
- Linus Pauling Institute, Oregon State University, Corvallis, OR
| | - Carmen P Wong
- School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR
- Linus Pauling Institute, Oregon State University, Corvallis, OR
| | - Zhenzhen Zhang
- OHSU-PSU School of Public Health, Oregon Health & Science University, Portland, OR
| | - David E Williams
- Linus Pauling Institute, Oregon State University, Corvallis, OR
- Department of Environmental and Molecular Toxicology, College of Agricultural Sciences, Oregon State University, Corvallis, OR
| | - Roderick H Dashwood
- Linus Pauling Institute, Oregon State University, Corvallis, OR
- Department of Environmental and Molecular Toxicology, College of Agricultural Sciences, Oregon State University, Corvallis, OR
| | - Jackilen Shannon
- Department of Environmental and Molecular Toxicology, College of Agricultural Sciences, Oregon State University, Corvallis, OR
| | - Philippe Thuillier
- OHSU-PSU School of Public Health, Oregon Health & Science University, Portland, OR
- Department of Dermatology, Oregon Health & Science University, Portland, OR
| | - Emily Ho
- School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR
- Linus Pauling Institute, Oregon State University, Corvallis, OR
- Moore Family Center for Whole Grain Foods, Nutrition and Preventive Health, Oregon State University, Corvallis, OR
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13
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Kim MB, Ko JY, Lim SB. Formulation Optimization of Antioxidant-Rich Juice Powders Based on Experimental Mixture Design. J FOOD PROCESS PRES 2017. [DOI: 10.1111/jfpp.12897] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Mi-Bo Kim
- Jeju Wellbeing Vegetables RIS System; Jeju National University; Jeju 690-756 Republic of Korea
| | - Jeong-Yeon Ko
- Department of Food Bioengineering; Jeju National University; Jeju 690-756 Republic of Korea
| | - Sang-Bin Lim
- Jeju Wellbeing Vegetables RIS System; Jeju National University; Jeju 690-756 Republic of Korea
- Department of Food Bioengineering; Jeju National University; Jeju 690-756 Republic of Korea
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Kim MJ, Chiu YC, Kim NK, Park HM, Lee CH, Juvik JA, Ku KM. Cultivar-Specific Changes in Primary and Secondary Metabolites in Pak Choi (Brassica Rapa, Chinensis Group) by Methyl Jasmonate. Int J Mol Sci 2017; 18:E1004. [PMID: 28481284 PMCID: PMC5454917 DOI: 10.3390/ijms18051004] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Revised: 05/01/2017] [Accepted: 05/02/2017] [Indexed: 11/16/2022] Open
Abstract
Glucosinolates, their hydrolysis products and primary metabolites were analyzed in five pak choi cultivars to determine the effect of methyl jasmonate (MeJA) on metabolite flux from primary metabolites to glucosinolates and their hydrolysis products. Among detected glucosinolates (total 14 glucosinolates; 9 aliphatic, 4 indole and 1 aromatic glucosinolates), indole glucosinolate concentrations (153-229%) and their hydrolysis products increased with MeJA treatment. Changes in the total isothiocyanates by MeJA were associated with epithiospecifier protein activity estimated as nitrile formation. Goitrin, a goitrogenic compound, significantly decreased by MeJA treatment in all cultivars. Changes in glucosinolates, especially aliphatic, significantly differed among cultivars. Primary metabolites including amino acids, organic acids and sugars also changed with MeJA treatment in a cultivar-specific manner. A decreased sugar level suggests that they might be a carbon source for secondary metabolite biosynthesis in MeJA-treated pak choi. The result of the present study suggests that MeJA can be an effective agent to elevate indole glucosinolates and their hydrolysis products and to reduce a goitrogenic compound in pak choi. The total glucosinolate concentration was the highest in "Chinese cabbage" in the control group (32.5 µmol/g DW), but indole glucosinolates increased the greatest in "Asian" when treated with MeJA.
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Affiliation(s)
- Moo Jung Kim
- Division of Plant and Soil Sciences, West Virginia University, Morgantown, WV 26506, USA.
| | - Yu-Chun Chiu
- Division of Plant and Soil Sciences, West Virginia University, Morgantown, WV 26506, USA.
| | - Na Kyung Kim
- Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Korea.
| | - Hye Min Park
- Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Korea.
| | - Choong Hwan Lee
- Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Korea.
| | - John A Juvik
- Department of Crop Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
| | - Kang-Mo Ku
- Division of Plant and Soil Sciences, West Virginia University, Morgantown, WV 26506, USA.
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Yi GE, Robin AHK, Yang K, Park JI, Hwang BH, Nou IS. Exogenous Methyl Jasmonate and Salicylic Acid Induce Subspecies-Specific Patterns of Glucosinolate Accumulation and Gene Expression in Brassica oleracea L. Molecules 2016; 21:molecules21101417. [PMID: 27783045 PMCID: PMC6273115 DOI: 10.3390/molecules21101417] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2016] [Revised: 10/18/2016] [Accepted: 10/19/2016] [Indexed: 01/18/2023] Open
Abstract
Glucosinolates have anti-carcinogenic properties. In the recent decades, the genetics of glucosinolate biosynthesis has been widely studied, however, the expression of specific genes involved in glucosinolate biosynthesis under exogenous phytohormone treatment has not been explored at the subspecies level in Brassica oleracea. Such data are vital for strategies aimed at selective exploitation of glucosinolate profiles. This study quantified the expression of 38 glucosinolate biosynthesis-related genes in three B. oleracea subspecies, namely cabbage, broccoli and kale, and catalogued associations between gene expression and increased contents of individual glucosinolates under methyl jasmonate (MeJA) and salicylic acid (SA) treatments. Glucosinolate accumulation and gene expression in response to phytohormone elicitation was subspecies specific. For instance, cabbage leaves showed enhanced accumulation of the aliphatic glucoiberin, progoitrin, sinigrin and indolic neoglucobrassicin under both MeJA and SA treatment. MeJA treatment induced strikingly higher accumulation of glucobrassicin (GBS) in cabbage and kale and of neoglucobrassicin (NGBS) in broccoli compared to controls. Notably higher expression of ST5a (Bol026200), CYP81F1 (Bol028913, Bol028914) and CYP81F4 genes was associated with significantly higher GBS accumulation under MeJA treatment compared to controls in all three subspecies. CYP81F4 genes, trans-activated by MYB34 genes, were expressed at remarkably high levels in all three subspecies under MeJA treatment, which also induced in higher indolic NGBS accumulation in all three subspecies. Remarkably higher expression of MYB28 (Bol036286), ST5b, ST5c, AOP2, FMOGS-OX5 (Bol031350) and GSL-OH (Bol033373) was associated with much higher contents of aliphatic glucosinolates in kale leaves compared to the other two subspecies. The genes expressed highly could be utilized in strategies to selectively increase glucosinolate compounds in B. oleracea subspecies. These results promote efforts to develop genotypes of B. oleracea and other species with enhanced levels of desired glucosinolates.
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Affiliation(s)
- Go-Eun Yi
- Department of Horticulture, Sunchon National University, Suncheon-si 540-950, Korea.
| | - Arif Hasan Khan Robin
- Department of Horticulture, Sunchon National University, Suncheon-si 540-950, Korea.
| | - Kiwoung Yang
- Department of Horticulture, Sunchon National University, Suncheon-si 540-950, Korea.
| | - Jong-In Park
- Department of Horticulture, Sunchon National University, Suncheon-si 540-950, Korea.
| | - Byung Ho Hwang
- R & D Center for Crop Breeding, Asia Seed Ltd., Icheon-si, Gyeonggi-do 467-906, Korea.
| | - Ill-Sup Nou
- Department of Horticulture, Sunchon National University, Suncheon-si 540-950, Korea.
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Villarreal-García D, Nair V, Cisneros-Zevallos L, Jacobo-Velázquez DA. Plants as Biofactories: Postharvest Stress-Induced Accumulation of Phenolic Compounds and Glucosinolates in Broccoli Subjected to Wounding Stress and Exogenous Phytohormones. FRONTIERS IN PLANT SCIENCE 2016; 7:45. [PMID: 26904036 PMCID: PMC4748037 DOI: 10.3389/fpls.2016.00045] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/04/2015] [Accepted: 01/11/2016] [Indexed: 05/24/2023]
Abstract
Broccoli contains high levels of bioactive molecules and is considered a functional food. In this study, postharvest treatments to enhance the concentration of glucosinolates and phenolic compounds were evaluated. Broccoli whole heads were wounded to obtain florets and wounded florets (florets cut into four even pieces) and stored for 24 h at 20 °C with or without exogenous ethylene (ET, 1000 ppm) or methyl jasmonate (MeJA, 250 ppm). Whole heads were used as a control for wounding treatments. Regarding glucosinolate accumulation, ET selectively induced the 4-hydroxylation of glucobrassicin in whole heads, resulting in ∼223% higher 4-hydroxyglucobrassicin than time 0 h samples. Additionally, glucoraphanin was increased by ∼53% in whole heads treated with ET, while neoglucobrassicin was greatly accumulated in wounded florets treated with ET or MeJA, showing increases of ∼193 and ∼286%, respectively. On the other hand, although only whole heads stored without phytohormones showed higher concentrations of phenolic compounds, which was reflected in ∼33, ∼30, and ∼46% higher levels of 1,2,2-trisinapoylgentiobose, 1,2-diferulolylgentiobiose, and 1,2-disinapoyl-2-ferulolylgentiobiose, respectively; broccoli florets stored under air control conditions showed enhanced concentrations of 3-O-caffeoylquinic acid, 1,2-disinapoylgentiobiose, and 1,2-disinapoyl-2-ferulolylgentiobiose (∼22, ∼185, and ∼65% more, respectively). Furthermore, exogenous ET and MeJA impeded individual phenolics accumulation. Results allowed the elucidation of simple and effective postharvest treatment to enhance the content of individual glucosinolates and phenolic compounds in broccoli. The stressed-broccoli tissue could be subjected to downstream processing in order to extract and purify bioactive molecules with applications in the dietary supplements, agrochemical and cosmetics markets.
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Affiliation(s)
| | - Vimal Nair
- Department of Horticultural Sciences, Texas A&M University, College StationTX, USA
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17
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Lee M, Yoon JH. Metabolic interplay between glycolysis and mitochondrial oxidation: The reverse Warburg effect and its therapeutic implication. World J Biol Chem 2015; 6:148-61. [PMID: 26322173 PMCID: PMC4549759 DOI: 10.4331/wjbc.v6.i3.148] [Citation(s) in RCA: 107] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2015] [Revised: 05/26/2015] [Accepted: 07/21/2015] [Indexed: 02/05/2023] Open
Abstract
Aerobic glycolysis, i.e., the Warburg effect, may contribute to the aggressive phenotype of hepatocellular carcinoma. However, increasing evidence highlights the limitations of the Warburg effect, such as high mitochondrial respiration and low glycolysis rates in cancer cells. To explain such contradictory phenomena with regard to the Warburg effect, a metabolic interplay between glycolytic and oxidative cells was proposed, i.e., the "reverse Warburg effect". Aerobic glycolysis may also occur in the stromal compartment that surrounds the tumor; thus, the stromal cells feed the cancer cells with lactate and this interaction prevents the creation of an acidic condition in the tumor microenvironment. This concept provides great heterogeneity in tumors, which makes the disease difficult to cure using a single agent. Understanding metabolic flexibility by lactate shuttles offers new perspectives to develop treatments that target the hypoxic tumor microenvironment and overcome the limitations of glycolytic inhibitors.
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