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Bohn T, Balbuena E, Ulus H, Iddir M, Wang G, Crook N, Eroglu A. Carotenoids in Health as Studied by Omics-Related Endpoints. Adv Nutr 2023; 14:1538-1578. [PMID: 37678712 PMCID: PMC10721521 DOI: 10.1016/j.advnut.2023.09.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 08/25/2023] [Accepted: 09/01/2023] [Indexed: 09/09/2023] Open
Abstract
Carotenoids have been associated with risk reduction for several chronic diseases, including the association of their dietary intake/circulating levels with reduced incidence of obesity, type 2 diabetes, certain types of cancer, and even lower total mortality. In addition to some carotenoids constituting vitamin A precursors, they are implicated in potential antioxidant effects and pathways related to inflammation and oxidative stress, including transcription factors such as nuclear factor κB and nuclear factor erythroid 2-related factor 2. Carotenoids and metabolites may also interact with nuclear receptors, mainly retinoic acid receptor/retinoid X receptor and peroxisome proliferator-activated receptors, which play a role in the immune system and cellular differentiation. Therefore, a large number of downstream targets are likely influenced by carotenoids, including but not limited to genes and proteins implicated in oxidative stress and inflammation, antioxidation, and cellular differentiation processes. Furthermore, recent studies also propose an association between carotenoid intake and gut microbiota. While all these endpoints could be individually assessed, a more complete/integrative way to determine a multitude of health-related aspects of carotenoids includes (multi)omics-related techniques, especially transcriptomics, proteomics, lipidomics, and metabolomics, as well as metagenomics, measured in a variety of biospecimens including plasma, urine, stool, white blood cells, or other tissue cellular extracts. In this review, we highlight the use of omics technologies to assess health-related effects of carotenoids in mammalian organisms and models.
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Affiliation(s)
- Torsten Bohn
- Nutrition and Health Research Group, Department of Precision Health, Luxembourg Institute of Health, Strassen, Luxembourg.
| | - Emilio Balbuena
- Department of Molecular and Structural Biochemistry, College of Agriculture and Life Sciences, North Carolina State University, Raleigh, NC, United States; Plants for Human Health Institute, North Carolina Research Campus, North Carolina State University, Kannapolis, NC, United States
| | - Hande Ulus
- Plants for Human Health Institute, North Carolina Research Campus, North Carolina State University, Kannapolis, NC, United States
| | - Mohammed Iddir
- Nutrition and Health Research Group, Department of Precision Health, Luxembourg Institute of Health, Strassen, Luxembourg
| | - Genan Wang
- Department of Chemical and Biomolecular Engineering, College of Engineering, North Carolina State University, Raleigh, NC, United States
| | - Nathan Crook
- Department of Chemical and Biomolecular Engineering, College of Engineering, North Carolina State University, Raleigh, NC, United States
| | - Abdulkerim Eroglu
- Department of Molecular and Structural Biochemistry, College of Agriculture and Life Sciences, North Carolina State University, Raleigh, NC, United States; Plants for Human Health Institute, North Carolina Research Campus, North Carolina State University, Kannapolis, NC, United States.
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2
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Wan L, Thomas-Ahner JM, Pearl DK, Erdman JW, Moran NE, Clinton SK. Orchestration of miRNA Patterns by Testosterone and Dietary Tomato Carotenoids during Early Prostate Carcinogenesis in TRAMP Mice. J Nutr 2023; 153:1877-1888. [PMID: 37187350 PMCID: PMC10375503 DOI: 10.1016/j.tjnut.2023.05.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 04/27/2023] [Accepted: 05/11/2023] [Indexed: 05/17/2023] Open
Abstract
BACKGROUND The integrative effects of prostate cancer risk factors, such as diet and endocrine status, on cancer-associated miRNA expression are poorly defined. OBJECTIVES This study aimed to define the influence of androgens and diet (tomato and lycopene) on prostatic miRNA expression during early carcinogenesis in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. METHODS Wild type (WT) and TRAMP mice were fed control, tomato-containing, or lycopene-containing diets from 4 to 10 weeks of age. Mice underwent either sham (intact) or castration surgery at 8 wk, and half of the castrated mice received testosterone (2.5 mg/kg body weight/d) at 9 wk. Mice were killed at 10 wk, and dorsolateral prostate expression of 602 miRNAs was assessed. RESULTS We detected expression of 88 miRNAs (15% of 602), all of which were present in the TRAMP, in comparison with 49 miRNAs being detectable (8%) in WT. Expression of 61 miRNAs differed by TRAMP genotype, with the majority upregulated in TRAMP. Of the 61 miRNAs, 42 were responsive to androgen status. Diet affected 41% of the miRNAs, which differed by genotype (25/61) and 48% of the androgen-sensitive miRNAs (20/42), indicating overlapping genetic and dietary influences on prostate miRNAs. Tomato and lycopene feeding influenced miRNAs previously associated with the regulation of androgen (miR-145 and let-7), MAPK (miR-106a, 204, 145/143, and 200b/c), and p53 signaling (miR-125 and miR-98) pathways. CONCLUSIONS Expression of miRNAs in early prostate carcinogenesis is sensitive to genetic, endocrine, and diet drivers, suggesting novel mechanisms by which tomato and lycopene feeding modulate early prostate carcinogenesis.
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Affiliation(s)
- Lei Wan
- The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; Interdisciplinary Nutrition Program
| | | | - Dennis K Pearl
- Department of Statistics, The Pennsylvania State University, University Park, PA, USA
| | - John W Erdman
- Department of Food Science and Human Nutrition, University of Illinois, Urbana, IL, USA
| | - Nancy E Moran
- The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
| | - Steven K Clinton
- The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
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3
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The In Vitro, Ex Vivo, and In Vivo Effect of Edible Oils: A Review on Cell Interactions. Pharmaceutics 2023; 15:pharmaceutics15030869. [PMID: 36986730 PMCID: PMC10056871 DOI: 10.3390/pharmaceutics15030869] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 02/23/2023] [Accepted: 03/01/2023] [Indexed: 03/11/2023] Open
Abstract
Consumption of edible oils is a significant part of the dietary pattern in the developed and developing world. Marine and vegetable oils are assumed to be part of a healthy food pattern, especially if one takes into account their potential role in protecting against inflammation, cardiovascular disease, and metabolic syndrome due to the presence of polyunsaturated fatty acids and minor bioactive compounds. Exploring the potential effect of edible fats and oils on health and chronic diseases is an emerging field worldwide. This study reviews the current knowledge of the in vitro, ex vivo, and in vivo effect of edible oils in contact with various cell types and aims to demonstrate which nutritional and bioactive components of a variety of edible oils present biocompatibility, antimicrobial properties, antitumor activity, anti-angiogenic activity, and antioxidant activity. Through this review, a wide variety of cell interactions with edible oils and their potential to counteract oxidative stress in pathological conditions are presented as well. Moreover, the gaps in current knowledge are also highlighted, and future perspectives on edible oils and their health benefits and potential to counteract a wide variety of diseases through possible molecular mechanisms are also discussed.
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Li J, Chen Y, Shi Q, Sun J, Zhang C, Liu L. Omega-3 polyunsaturated fatty acids ameliorate PM2.5 exposure induced lung injury in mice through remodeling the gut microbiota and modulating the lung metabolism. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023; 30:40490-40506. [PMID: 36609968 PMCID: PMC9822699 DOI: 10.1007/s11356-022-25111-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Accepted: 12/29/2022] [Indexed: 06/17/2023]
Abstract
Short-term or long-term exposure to fine particulate matter (PM2.5) is related to increased incidences of respiratory diseases. This study aimed to investigate the influences of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) supplementation on oxidative stress, inflammation, lung metabolic profile, and gut microbiota in PM2.5-induced lung injury mice. Mice were divided into four groups (n = 15, per group): two unsupplemented groups, control group and PM2.5 group, and two supplemented groups with ω-3 PUFAs, ω-3 PUFAs group, and ω-3 PUFAs + PM2.5 group. Mice in the supplemented groups were placed on an ω-3 PUFAs-enriched diet (ω-3 PUFAs, 21 g/kg). During the 5th to 6th week of dietary supplementation, mice were exposed to PM2.5 by intra-tracheal instillation. ω-3 PUFAs ameliorate lung histopathological injury, reduce inflammatory responses and oxidative stress, affect lung metabolite profile, and modulate gut microbiota in PM2.5-induced lung injury mice. Thus, supplementary ω-3 PUFAs showed effectiveness in attenuation of PM2.5-induced lung injury, indicating that the interventions exhibited preventive and therapeutic potential.
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Affiliation(s)
- Jingli Li
- Department of Pulmonary and Critical Care Medicine, Shaoxing People's Hospital, Shaoxing, 312000, Zhejiang, China
| | - Yang Chen
- Department of Critical Care Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China
| | - Qiangqiang Shi
- Department of Respiratory Medicine, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, 322100, Zhejiang, China
| | - Jian Sun
- Department of Pulmonary and Critical Care Medicine, Shaoxing People's Hospital, Shaoxing, 312000, Zhejiang, China
| | - Chunyi Zhang
- Department of Pulmonary and Critical Care Medicine, Shaoxing People's Hospital, Shaoxing, 312000, Zhejiang, China
| | - Lingjing Liu
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
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The Regulatory Effect of Phytochemicals on Chronic Diseases by Targeting Nrf2-ARE Signaling Pathway. Antioxidants (Basel) 2023; 12:antiox12020236. [PMID: 36829795 PMCID: PMC9952802 DOI: 10.3390/antiox12020236] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/15/2023] [Accepted: 01/17/2023] [Indexed: 01/22/2023] Open
Abstract
Redox balance is essential to maintain the body's normal metabolism. Once disrupted, it may lead to various chronic diseases, such as diabetes, neurodegenerative diseases, cardiovascular diseases, inflammatory diseases, cancer, aging, etc. Oxidative stress can cause or aggravate a series of pathological processes. Inhibition of oxidative stress and related pathological processes can help to ameliorate these chronic diseases, which have been found to be associated with Nrf2 activation. Nrf2 activation can not only regulate the expression of a series of antioxidant genes that reduce oxidative stress and its damage, but also directly regulate genes related to the above-mentioned pathological processes to counter the corresponding changes. Therefore, targeting Nrf2 has great potential for the prevention or treatment of chronic diseases, and many natural phytochemicals have been reported as Nrf2 activators although the defined mechanisms remain to be elucidated. This review article focuses on the possible mechanism of Nrf2 activation by natural phytochemicals in the prevention or treatment of chronic diseases and the regulation of oxidative stress. Moreover, the current clinical trials of phytochemical-originated drug discovery by targeting the Nrf2-ARE pathway were also summarized; the outcomes or the relationship between phytochemicals and chronic diseases prevention are finally analyzed to propose the future research strategies and prospective.
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The Anti-Cancer Activity of Lycopene: A Systematic Review of Human and Animal Studies. Nutrients 2022; 14:nu14235152. [PMID: 36501182 PMCID: PMC9741066 DOI: 10.3390/nu14235152] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 11/25/2022] [Accepted: 11/29/2022] [Indexed: 12/10/2022] Open
Abstract
Lycopene is a nutraceutical with health-promoting and anti-cancer activities, but due to a lack of evidence, there are no recommendations regarding its use and dosage. This review aimed to evaluate the benefits of lycopene supplementation in cancer prevention and treatment based on the results of in vivo studies. We identified 72 human and animal studies that were then analysed for endpoints such as cancer incidence, improvement in treatment outcomes, and the mechanisms of lycopene action. We concluded that the results of most of the reviewed in vivo studies confirmed the anti-cancer activities of lycopene. Most of the studies concerned prostate cancer, reflecting the number of in vitro studies. The reported mechanisms of lycopene action in vivo included regulation of oxidative and inflammatory processes, induction of apoptosis, and inhibition of cell division, angiogenesis, and metastasis formation. The predominance of particular mechanisms seemed to depend on tumour organ localisation and the local storage capacity of lycopene. Finally, there is a need to look for predictive factors to identify a population that may benefit from lycopene supplementation. The potential candidates appear to be race, single nucleotide polymorphisms in carotene-cleaving enzymes, some genetic abbreviations, and insulin-like growth factor-dependent and inflammatory diseases.
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Affiliation(s)
- Sandro La Vignera
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Livia Basile
- Department of Chemical Sciences, University of Catania, Catania, Italy
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Marzocco S, Singla RK, Capasso A. Multifaceted Effects of Lycopene: A Boulevard to the Multitarget-Based Treatment for Cancer. Molecules 2021; 26:molecules26175333. [PMID: 34500768 PMCID: PMC8434243 DOI: 10.3390/molecules26175333] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 08/29/2021] [Accepted: 08/29/2021] [Indexed: 02/05/2023] Open
Abstract
Lycopene is a pigment belonging to the group of carotenoids and it is among the most carefully studied antioxidants found especially in fruit and vegetables. As a carotenoid, lycopene exerts beneficial effects on human health by protecting lipids, proteins, and DNA from damage by oxidation. Lycopene is a powerful oxygen inactivator in the singlet state. This is suggestive of the fact that lycopene harbors comparatively stronger antioxidant properties over other carotenoids normally present in plasma. Lycopene is also reported to hinder cancer cell proliferation. The uncontrolled, rapid division of cells is a characteristic of the metabolism of cancer cells. Evidently, lycopene causes a delay in the progression of the cell cycle, which explains its antitumor activity. Furthermore, lycopene can block cell transformation by reducing the loss of contact inhibition of cancer cells. This paper collects recent studies of scientific evidence that show the multiple beneficial properties of lycopene, which acts with different molecular and cellular mechanisms.
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Affiliation(s)
- Stefania Marzocco
- Department of Pharmacy, University of Salerno, 84084 Fisciano, Italy;
- Correspondence: ; Tel.: +39-089-96-92-50
| | - Rajeev K. Singla
- Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China;
- iGlobal Research and Publishing Foundation, New Delhi 110059, India
| | - Anna Capasso
- Department of Pharmacy, University of Salerno, 84084 Fisciano, Italy;
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Dulińska-Litewka J, Sharoni Y, Hałubiec P, Łazarczyk A, Szafrański O, McCubrey JA, Gąsiorkiewicz B, Laidler P, Bohn T. Recent Progress in Discovering the Role of Carotenoids and Their Metabolites in Prostatic Physiology and Pathology with a Focus on Prostate Cancer-A Review-Part I: Molecular Mechanisms of Carotenoid Action. Antioxidants (Basel) 2021; 10:antiox10040585. [PMID: 33920256 PMCID: PMC8069951 DOI: 10.3390/antiox10040585] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 04/05/2021] [Accepted: 04/07/2021] [Indexed: 12/13/2022] Open
Abstract
Among the vast variety of plant-derived phytochemicals, the group of carotenoids has continuously been investigated in order to optimize their potential application in the area of dietary intervention and medicine. One organ which has been especially targeted in many of these studies and clinical trials is the human prostate. Without doubt, carotenoids (and their endogenous derivatives—retinoids and other apo-carotenoids) are involved in intra- and intercellular signaling, cell growth and differentiation of prostate tissue. Due to the accumulation of new data on the role of different carotenoids such as lycopene (LC) and β-carotene (BC) in prostatic physiology and pathology, the present review aims to cover the past ten years of research in this area. Data from experimental studies are presented in the first part of the review, while epidemiological studies are disclosed and discussed in the second part. The objective of this compilation is to emphasize the present state of knowledge regarding the most potent molecular targets of carotenoids and their main metabolites, as well as to propose promising carotenoid agents for the prevention and treatment of prostatic diseases.
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Affiliation(s)
- Joanna Dulińska-Litewka
- Medical Biochemistry Medical College, Jagiellonian University, 31-034 Cracow, Poland; (P.H.); (A.Ł.); (O.S.); (B.G.); (P.L.)
- Correspondence: ; Tel.: +48-12-422-3272
| | - Yoav Sharoni
- Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653 Beer Sheva, Israel;
| | - Przemysław Hałubiec
- Medical Biochemistry Medical College, Jagiellonian University, 31-034 Cracow, Poland; (P.H.); (A.Ł.); (O.S.); (B.G.); (P.L.)
| | - Agnieszka Łazarczyk
- Medical Biochemistry Medical College, Jagiellonian University, 31-034 Cracow, Poland; (P.H.); (A.Ł.); (O.S.); (B.G.); (P.L.)
| | - Oskar Szafrański
- Medical Biochemistry Medical College, Jagiellonian University, 31-034 Cracow, Poland; (P.H.); (A.Ł.); (O.S.); (B.G.); (P.L.)
| | - James A. McCubrey
- Department of Microbiology and Immunology, Brody Medical Sciences Building, East Carolina University, Greenville, NC 27834, USA;
| | - Bartosz Gąsiorkiewicz
- Medical Biochemistry Medical College, Jagiellonian University, 31-034 Cracow, Poland; (P.H.); (A.Ł.); (O.S.); (B.G.); (P.L.)
| | - Piotr Laidler
- Medical Biochemistry Medical College, Jagiellonian University, 31-034 Cracow, Poland; (P.H.); (A.Ł.); (O.S.); (B.G.); (P.L.)
| | - Torsten Bohn
- Nutrition and Health Research Group, Department of Population Health, Luxembourg Institute of Health, 1 A-B, rue Thomas Edison, L-23 1445 Strassen, Luxembourg;
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Gregg JR, Zhang X, Chapin B, Ward J, Kim J, Davis J, Daniel CR. Adherence to the Mediterranean diet and grade group progression in localized prostate cancer: An active surveillance cohort. Cancer 2021; 127:720-728. [PMID: 33411364 PMCID: PMC9810094 DOI: 10.1002/cncr.33182] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Revised: 06/23/2020] [Accepted: 07/23/2020] [Indexed: 01/07/2023]
Abstract
BACKGROUND The Mediterranean diet (MD) may be beneficial for men with localized prostate cancer (PCa) on active surveillance (AS) because of its anti-inflammatory, antilipidemic, and chemopreventive properties. This study prospectively investigated adherence to the MD with Gleason score progression and explored associations by diabetes status, statin use, and other factors. METHODS Men with newly diagnosed PCa on an AS protocol (n = 410) completed a baseline food frequency questionnaire, and the MD score was calculated across 9 energy-adjusted food groups. Cox proportional hazards models were fit to evaluate multivariable-adjusted associations of the MD score with progression-free survival; progression was defined as an increase in the Gleason grade group (GG) score over a biennial monitoring regimen. RESULTS In this cohort, 15% of the men were diabetic, 44% of the men used statins, and 76 men progressed (median follow-up, 36 months). After adjustments for clinical factors, higher adherence to the MD was associated with a lower risk of GG progression among all men (hazard ratio [HR] per 1-unit increase in MD score, 0.88; 95% confidence interval [CI], 0.77-1.01), non-White men (HR per 1-unit increase in MD score, 0.64; 95% CI, 0.45-0.92; P for interaction = .07), and men without diabetes (HR per 1-unit increase in MD score, 0.82; 95% CI, 0.71-0.96; P for interaction = .03). When joint effects of the MD score and statin use were examined, a similar risk reduction was observed among men with high MD scores who did not use statins in comparison with men with low/moderate MD scores with no statin use. CONCLUSIONS The MD is associated with a lower risk of GG progression in men on AS, and this is consistent with prior reports about the MD and reduced cancer morbidity and mortality.
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Affiliation(s)
- Justin R. Gregg
- University of Texas MD Anderson Cancer Center, Houston, TX,Joint Corresponding authors: Justin R. Gregg, MD, Mailing address: 1155 Pressler Street, Unit 1373, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, , Phone: 713-563-1432, Fax: 713-794-4824, Carrie R. Daniel, PhD, Mailing address: 1155 Pressler Street, Unit 1340, Room CPB4.3241, Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, , Phone: 713-563-5783, Fax: 713-563-1367
| | - Xiaotao Zhang
- University of Texas MD Anderson Cancer Center, Houston, TX
| | - Brian Chapin
- University of Texas MD Anderson Cancer Center, Houston, TX
| | | | - Jeri Kim
- Merck & Co., Inc. Kenilworth, NJ
| | - John Davis
- University of Texas MD Anderson Cancer Center, Houston, TX
| | - Carrie R. Daniel
- University of Texas MD Anderson Cancer Center, Houston, TX,Joint Corresponding authors: Justin R. Gregg, MD, Mailing address: 1155 Pressler Street, Unit 1373, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, , Phone: 713-563-1432, Fax: 713-794-4824, Carrie R. Daniel, PhD, Mailing address: 1155 Pressler Street, Unit 1340, Room CPB4.3241, Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, , Phone: 713-563-5783, Fax: 713-563-1367
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11
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Clifford T, Acton JP, Cocksedge SP, Davies KAB, Bailey SJ. The effect of dietary phytochemicals on nuclear factor erythroid 2-related factor 2 (Nrf2) activation: a systematic review of human intervention trials. Mol Biol Rep 2021; 48:1745-1761. [PMID: 33515348 PMCID: PMC7925463 DOI: 10.1007/s11033-020-06041-x] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 11/28/2020] [Indexed: 01/06/2023]
Abstract
We conducted a systematic review of human trials examining the effects of dietary phytochemicals on Nrf2 activation. In accordance with the PRISMA guidelines, Medline, Embase and CAB abstracts were searched for articles from inception until March 2020. Studies in adult humans that measured Nrf2 activation (gene or protein expression changes) following ingestion of a phytochemical, either alone or in combination were included. The study was pre-registered on the Prospero database (Registration Number: CRD42020176121). Twenty-nine full-texts were retrieved and reviewed for analysis; of these, eighteen were included in the systematic review. Most of the included participants were healthy, obese or type 2 diabetics. Study quality was assessed using the Cochrane Collaboration Risk of Bias Assessment tool. Twelve different compounds were examined in the included studies: curcumin, resveratrol and sulforaphane were the most common (n = 3 each). Approximately half of the studies reported increases in Nrf2 activation (n = 10); however, many were of poor quality and had an unclear or high risk of bias. There is currently limited evidence that phytochemicals activate Nrf2 in humans. Well controlled human intervention trials are needed to corroborate the findings from in vitro and animal studies.
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Affiliation(s)
- Tom Clifford
- School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, LE11 3TU, UK.
| | - Jarred P Acton
- School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, LE11 3TU, UK
| | - Stuart P Cocksedge
- School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, LE11 3TU, UK
| | - Kelly A Bowden Davies
- Department of Sport and Exercise Sciences, Manchester Metropolitan University, Manchester, M15 6BH, UK
| | - Stephen J Bailey
- School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, LE11 3TU, UK
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12
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Grammatikopoulou MG, Gkiouras K, Papageorgiou SΤ, Myrogiannis I, Mykoniatis I, Papamitsou T, Bogdanos DP, Goulis DG. Dietary Factors and Supplements Influencing Prostate Specific-Antigen (PSA) Concentrations in Men with Prostate Cancer and Increased Cancer Risk: An Evidence Analysis Review Based on Randomized Controlled Trials. Nutrients 2020; 12:nu12102985. [PMID: 33003518 PMCID: PMC7600271 DOI: 10.3390/nu12102985] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 09/19/2020] [Accepted: 09/24/2020] [Indexed: 12/15/2022] Open
Abstract
The quest for dietary patterns and supplements efficient in down-regulating prostate-specific antigen (PSA) concentrations among men with prostate cancer (PCa) or increased PCa risk has been long. Several antioxidants, including lycopene, selenium, curcumin, coenzyme Q10, phytoestrogens (including isoflavones and flavonoids), green tea catechins, cernitin, vitamins (C, E, D) and multivitamins, medicinal mushrooms (Ganoderma lucidum), fruit extracts (saw palmetto, cranberries, pomegranate), walnuts and fatty acids, as well as combined supplementations of all, have been examined in randomized controlled trials (RCTs) in humans, on the primary, secondary, and tertiary PCa prevention level. Despite the plethora of trials and the variety of examined interventions, the evidence supporting the efficacy of most dietary factors appears inadequate to recommend their use.
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Affiliation(s)
- Maria G. Grammatikopoulou
- Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, GR-41334 Larissa, Greece; (M.G.G.); (D.P.B.)
| | - Konstantinos Gkiouras
- Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, GR-41334 Larissa, Greece; (M.G.G.); (D.P.B.)
- Medical School, Faculty of Health Sciences, Aristotle University of Thessaloniki, University Campus, GR-54124 Thessaloniki, Greece; (S.Τ.P.); (I.M.)
- Correspondence: (K.G.); (D.G.G.)
| | - Stefanos Τ. Papageorgiou
- Medical School, Faculty of Health Sciences, Aristotle University of Thessaloniki, University Campus, GR-54124 Thessaloniki, Greece; (S.Τ.P.); (I.M.)
| | - Ioannis Myrogiannis
- Medical School, Faculty of Health Sciences, Aristotle University of Thessaloniki, University Campus, GR-54124 Thessaloniki, Greece; (S.Τ.P.); (I.M.)
| | - Ioannis Mykoniatis
- Institute for the Study of Urological Diseases (ISUD), 33 Nikis Avenue, GR-54622 Thessaloniki, Greece;
- 1st Department of Urology and Center for Sexual and Reproductive Health, G. Gennimatas—Aghios Demetrius General Hospital, 41 Ethnikis Amynis Street, Aristotle University of Thessaloniki, GR-54635 Thessaloniki, Greece
| | - Theodora Papamitsou
- Laboratory of Histology and Embryology, Medical School, Faculty of Health Sciences, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece;
| | - Dimitrios P. Bogdanos
- Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, GR-41334 Larissa, Greece; (M.G.G.); (D.P.B.)
- Division of Transplantation, Immunology and Mucosal Biology, MRC Centre for Transplantation, King’s College London Medical School, London SE5 9RS, UK
| | - Dimitrios G. Goulis
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Faculty of Health Sciences, Aristotle University of Thessaloniki, GR-56429 Thessaloniki, Greece
- Correspondence: (K.G.); (D.G.G.)
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Carica papaya: comprehensive overview of the nutritional values, phytochemicals and pharmacological activities. ADVANCES IN TRADITIONAL MEDICINE 2020. [DOI: 10.1007/s13596-020-00481-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Mirahmadi M, Azimi-Hashemi S, Saburi E, Kamali H, Pishbin M, Hadizadeh F. Potential inhibitory effect of lycopene on prostate cancer. Biomed Pharmacother 2020; 129:110459. [PMID: 32768949 DOI: 10.1016/j.biopha.2020.110459] [Citation(s) in RCA: 94] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 06/13/2020] [Accepted: 06/23/2020] [Indexed: 12/12/2022] Open
Abstract
Studying prostate cancer is important due to its high annual incidences and mortality rates in the world. Although prostate cancer mortality rates are reduced using new therapy, complicated routes and side effects of these current drugs require a daily available treatment for prevention. Lycopene is a natural, prominent, and effective product which has a high value in diet. The anti-cancer effect, non-toxicity, safety and preventive or therapeutic roles of lycopene have been investigated in several studies. In the current review, we have collected information about the anti-cancer, anti-progressive and apoptotic effects of lycopene on prostate cancer. This article is a summary of the most important original and review articles on lycopene and its anticancer effects that are systematically categorized and presents information about the molecular structure, different sources, biological functions, and its in-vivo and in-vitro effects of lycopene on variety of cancerous and normal cells. The clinical studies provide a clear image for continuous use of this adjunctive dietary for different type of cancers, especially prostate cancer in men. In addition, this article discusses the various molecular pathways activated by lycopene that eventually prevent or suppress cancer. Lycopene has been found to effectively suppress the progression and proliferation, arrest in-cell cycle, and induce apoptosis of prostate cancer cells in both in-vivo and in-vitro conditions. Additionally, lycopene showed that it could modulate the signaling pathways and their protein for the treatment or prevention of prostate cancer.
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Affiliation(s)
- Mahdi Mirahmadi
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Cancer Research, Nastran Center for Cancer Prevention (NCCP), Mashhad, Iran
| | - Shayan Azimi-Hashemi
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ehsan Saburi
- Medical Genetics and Molecular Medicine Department, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Kamali
- Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mandana Pishbin
- Iranian Blood Transfusion Organization, Khorasan Razavi Center, Mashhad, Iran
| | - Farzin Hadizadeh
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
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Jung SJ, Kim WL, Park BH, Lee SO, Chae SW. Effect of toxic trace element detoxification, body fat reduction following four-week intake of the Wellnessup diet: a three-arm, randomized clinical trial. Nutr Metab (Lond) 2020; 17:47. [PMID: 32582363 PMCID: PMC7310262 DOI: 10.1186/s12986-020-00465-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Accepted: 05/29/2020] [Indexed: 12/17/2022] Open
Abstract
Background Detox diet are known as a popular dieting strategies that helps toxins elimination and weight manage but there is very little clinical evidence. The Wellnessup diet (WD) used in the present study designed as a healthy meals based on organic plant based diets including various vegetables, fruits, whole grains, nuts and phytonutrients. Methods To evaluate the effects of 4 week intake of the WD on toxic trace element detoxification, body fat reduction, and safety parameters. Forty-five women with body mass index (BMI) of 23.5-30 kg/m2 were recruited. Thirty of them were assigned 1:1 to the test group (WD, 15 subjects) and control group 1 (calorie-restricted diet, CRD, 15 subjects) in a single blind and randomized, and the remaining 15 subjects were assigned to control group 2 (maintaining regular diet, MRD). The primary outcome were toxic trace element levels in hair (29 types of heavy metals), and the secondary outcomes were changes in anthropometric and urinary organic acids. Results The levels of four toxic trace elements in hair decreased in the WD group after the diet compared to before the diet. Ni, Rh, Sn, and Ga were significantly lower in the WD group than in the CRD or MRD group (p < 0.05). At the end of the trial, both WD and CRD groups had lower BMI, Waist Circumference(WC), Hip Circumference(HC) and WHR compared to the baseline values (p < 0.05). Compared to the WD group, the CRD group had a greater mean change (p < 0.05) from the baseline for weight loss (- 3.22 ± 0.48 kg vs - 1.88 ± 0.95 kg vs) and fat free mass (- 2.08 kg vs - 1.09 kg). The weight, BMI, body fat mass, fat free mass, WC, and HC of the CRD group were significantly decreased compared to the MRD (p < 0.05). No significant changes in any safety parameter were observed. Conclusions Use of WD might have several beneficial effects and safety such as body fat reduction and improving some the element detoxification through caloric restriction but did not reducing body fat mass more than calorie-restricted diet. Trial registration This study was registered at Clinical Research Information Service (CRIS) of Republic of Korea (KCT0003002).
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Affiliation(s)
- Su-Jin Jung
- Clinical Trial Center for Functional Foods, Chonbuk National University Hospital, Jeonju, Jeonbuk 54907 South Korea.,Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Jeonbuk 54907 South Korea
| | - Woo-Lim Kim
- Clinical Trial Center for Functional Foods, Chonbuk National University Hospital, Jeonju, Jeonbuk 54907 South Korea
| | - Byung-Hyun Park
- Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Jeonbuk 54907 South Korea.,Department of Biochemistry and Molecular Biology, Chonbuk National University Medical School, Jeonju, Jeonbuk 54896 South Korea
| | - Seung-Ok Lee
- Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Jeonbuk 54907 South Korea.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk 54896 South Korea
| | - Soo-Wan Chae
- Clinical Trial Center for Functional Foods, Chonbuk National University Hospital, Jeonju, Jeonbuk 54907 South Korea.,Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Jeonbuk 54907 South Korea.,Department of Pharmacology, Chonbuk National University Medical School, 567 Baekje-daero, Deokjin, Jeonju, Jeonbuk 54896 South Korea
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16
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Yurko-Mauro K, Van Elswyk M, Teo L. A Scoping Review of Interactions between Omega-3 Long-Chain Polyunsaturated Fatty Acids and Genetic Variation in Relation to Cancer Risk. Nutrients 2020; 12:E1647. [PMID: 32498320 PMCID: PMC7352171 DOI: 10.3390/nu12061647] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 05/26/2020] [Accepted: 05/28/2020] [Indexed: 02/06/2023] Open
Abstract
This scoping review examines the interaction of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) and genetic variants of various types of cancers. A comprehensive search was performed to identify controlled and observational studies conducted through August 2017. Eighteen unique studies were included: breast cancer (n = 2), gastric cancer (n = 1), exocrine pancreatic cancer (n = 1), chronic lymphocytic leukemia (n = 1), prostate cancer (n = 7) and colorectal cancer (n = 6). An additional 13 studies that focused on fish intake or at-risk populations were summarized to increase readers' understanding of the topic based on this review, DHA and EPA interact with certain genetic variants to decrease breast, colorectal and prostate cancer risk, although data was limited and identified polymorphisms were heterogeneous. The evidence to date demonstrates that omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) may decrease cancer risk by affecting genetic variants of inflammatory pathways, oxidative stress and tumor apoptosis. Collectively, data supports the notion that once a genetic variant is identified, the benefits of a targeted, personalized therapeutic regimen that includes DHA and/or EPA should be considered.
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Affiliation(s)
| | | | - Lynn Teo
- Teo Research Consulting, Silver Spring, MD, 20910, USA;
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17
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Sauter ER. Cancer prevention and treatment using combination therapy with natural compounds. Expert Rev Clin Pharmacol 2020; 13:265-285. [PMID: 32154753 DOI: 10.1080/17512433.2020.1738218] [Citation(s) in RCA: 106] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Introduction: Naturally occurring compounds play an essential role in the prevention and treatment of various cancers. There are more than 100 plant and animal based natural compounds currently in clinical use.Areas covered: 1) The importance of natural products combinations in the prevention and treatment of cancer, 2) the need to maximize efficacy while minimizing side effects when using natural product combinations, and 3) specifics related to plant and animal derived natural products, as well as agents derived from natural products. Therapies using natural compounds that have been investigated, their rationale, mechanism of action and findings are reviewed. When the data warrant it, combined interventions that appear to increase efficacy (compared with monotherapy) while minimizing toxicity have been highlighted. Pubmed was used to search for relevant publications.Expert opinion: Combination therapy with natural compounds has the potential to be more effective than single agent therapy. Similar to pharmacologic agents, the goal is to maximize efficacy while mimimizing potential side effects. There is an increasing research focus on the development of agents derived from natural products, with notable successes already achieved from the effort.
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Affiliation(s)
- Edward R Sauter
- Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA
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18
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Diet and lifestyle considerations for patients with prostate cancer. Urol Oncol 2019; 38:105-117. [PMID: 31327752 DOI: 10.1016/j.urolonc.2019.06.018] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2019] [Revised: 06/10/2019] [Accepted: 06/21/2019] [Indexed: 12/20/2022]
Abstract
PURPOSE To review the literature and provide recommendations on diet and lifestyle considerations in patients with prostate cancer using evidence from randomized controlled trials (RCTs) with additional considerations based on observational evidence. MATERIALS AND METHODS We initiated our search on ClinicalTrials.gov combining the term "prostate cancer" with a variety of diet and lifestyle factors. We then supplemented our summary of publications from registered trials by including other publications available on Pubmed. RESULTS There is a well-established benefit of exercise for improving functional outcomes and pelvic floor muscle training for improving treatment-related adverse effects. Multimodality interventions that integrate several factors (e.g., low-saturated fat, plant-based, whole-food diets with exercise, and stress reduction) appear to have the most clinically significant benefit for patients with prostate cancer. Ongoing multimodality interventions are including the efficacy of implementation strategies as observed outcomes. Limited RCT evidence suggests a clinically significant benefit for guided imagery/progressive muscle relaxation, Pilates, and lycopene-rich diets and a modest benefit for green tea, qigong, massage, and avoidance of nonprescribed vitamin and mineral supplements. Observational and single arm trial evidence indicates a need for further exploration of acupuncture, coffee, cruciferous vegetables, fish, Larrea tridentata, mushrooms, and vegetable-derived fats and avoidance of eggs, dairy, poultry with skin, processed red meat, and saturated fat. Published trials suggest no benefit from hypnosis, milk thistle, pomegranate, soy, or omega-3 fatty acid supplementation. CONCLUSIONS Our search demonstrated that most diet and lifestyle factors identified from observational studies have limited data from RCTs. Few items have shown early evidence of benefit. The best recommendation for patients with prostate cancer is to form a habit of wellness through healthy eating, aerobic and resistance exercise, and psychological well-being. Future trial development should consider how interventions can be implemented into real world practice.
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Hedayati N, Naeini MB, Nezami A, Hosseinzadeh H, Wallace Hayes A, Hosseini S, Imenshahidi M, Karimi G. Protective effect of lycopene against chemical and natural toxins: A review. Biofactors 2019; 45:5-23. [PMID: 30339717 DOI: 10.1002/biof.1458] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 09/02/2018] [Accepted: 09/06/2018] [Indexed: 12/25/2022]
Abstract
People are exposed to a number of environmental, occupational, and therapeutic toxic agents which may be natural or man made. These hazardous substances may manifest as direct side effects on the function of organs or indirectly induced alteration of gene expression, cancer-associated metabolic pathways, and/or alter homeostasis. Lycopene, as a one of the most potent antioxidant, is found in fruits and vegetables. High-intake of lycopene has been shown to be effective in decreasing the risk of both natural toxins including mycotoxins, bacterial toxins, and chemical toxins including heavy metals, pesticides as well as herbicides. Recently, there is growing attention in understanding the mechanisms of the phytochemicals and carotenoids as antioxidative, antiapoptotic, radical scavenging, and chelating agents and their roles in the modulation of inflammatory pathways. This review summarizes available data from several recent studies about lycopene and its role against chemical and natural toxicants. © 2018 BioFactors, 45(1):5-23, 2019.
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Affiliation(s)
- Narges Hedayati
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mehri Bemani Naeini
- Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Alireza Nezami
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Hosseinzadeh
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - A Wallace Hayes
- University of South Florida College of Public Health, Tampa, FL, USA
- Michigan State University Institute for Integrative Toxicology, East Lansing, MI, USA
| | - Sarasadat Hosseini
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohsen Imenshahidi
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gholamreza Karimi
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
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Reed D, Raina K, Agarwal R. Nutraceuticals in prostate cancer therapeutic strategies and their neo-adjuvant use in diverse populations. NPJ Precis Oncol 2018; 2:15. [PMID: 30062144 PMCID: PMC6060229 DOI: 10.1038/s41698-018-0058-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Revised: 06/18/2018] [Accepted: 06/21/2018] [Indexed: 12/17/2022] Open
Abstract
Prostate cancer (PCa) is the most frequently diagnosed malignancy and second leading cause of cancer mortality in American males. Notably, men of African descent in the United States and Caribbean have the highest PCa mortality rates compared to men with European ancestry. Although current therapeutics are quite potent and effective, disease resistance, progression to metastasis, therapy-associated toxicities and efficacy-related issues in diverse populations develop over time. Thus, non-toxic and efficacious therapeutic strategies are needed to address these major obstacles for the clinical treatment and management of PCa. In this regard, preclinical and population-based efficacy studies have shown the potential of natural non-toxic nutraceuticals as potent anti-PCa agents. Accordingly, the implementation of nutraceutical intervention and genetic testing in diverse populations might aid in the development and design of precision medicine strategies to reduce the burden of chemotherapy-associated toxicities, suppress disease resistance, and treat both localized and advanced PCa. Consequently, additional large-scale and inclusive clinical studies are required to fully assess efficacy and therapeutic limitations of these agents in PCa. This review discusses the most current clinical research on selected nutraceutical agents and their efficacy in the context of clinico-pathological outcomes and disease susceptibility in diverse PCa clinical and epidemiological studies.
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Affiliation(s)
- Dominique Reed
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO USA
| | - Komal Raina
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO USA
- University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO USA
| | - Rajesh Agarwal
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO USA
- University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO USA
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21
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Esgalhado M, Stenvinkel P, Mafra D. Nonpharmacologic Strategies to Modulate Nuclear Factor Erythroid 2–related Factor 2 Pathway in Chronic Kidney Disease. J Ren Nutr 2017; 27:282-291. [DOI: 10.1053/j.jrn.2017.01.022] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2016] [Revised: 11/03/2016] [Accepted: 01/06/2017] [Indexed: 01/25/2023] Open
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Kim HS, Kacew S, Lee BM. Genetic and epigenetic cancer chemoprevention on molecular targets during multistage carcinogenesis. Arch Toxicol 2016; 90:2389-2404. [PMID: 27538406 DOI: 10.1007/s00204-016-1813-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2016] [Accepted: 08/04/2016] [Indexed: 12/16/2022]
Abstract
The main goal of cancer chemoprevention is to prevent or halt the progression of carcinogenesis with the administration of synthetic or natural compounds. Fundamental chemopreventive strategies include inhibition of genetic damage, anti-proliferation/cell cycle regulation, and induction of apoptosis and anti-inflammatory processes, which may be critical for carcinogenesis intervention. Recently, a new paradigm for identifying chemopreventive agents has been implemented. It focuses on defining new biomarkers that can be used to evaluate chemopreventive efficacy based on multistage carcinogenesis. The functional roles of chemopreventive agents are associated with the modulation of nuclear factor kappa B, nuclear factor erythroid 2-related factor, p53, AMPK/mTOR, phosphatidylinositol 3-kinase, epidermal growth factor receptor, cyclooxygenase-2, chemokine (C-X-C motif) receptor 2, and sphingosine-1-phosphate. This paper summarizes the genetic and epigenetic effects of chemopreventive agents on the expression of cancer-related target genes mediated by epigenetic alterations, such as DNA methylation and histone modifications. This review will provide unique and effective strategies for reducing cancer and aging-related diseases in humans.
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Affiliation(s)
- Hyung Sik Kim
- Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Seoburo 2066, Suwon, Gyeonggi-Do, 440-746, Republic of Korea
| | - Sam Kacew
- McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, ON, Canada
| | - Byung Mu Lee
- Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Seoburo 2066, Suwon, Gyeonggi-Do, 440-746, Republic of Korea.
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Graff RE, Pettersson A, Lis RT, Ahearn TU, Markt SC, Wilson KM, Rider JR, Fiorentino M, Finn S, Kenfield SA, Loda M, Giovannucci EL, Rosner B, Mucci LA. Dietary lycopene intake and risk of prostate cancer defined by ERG protein expression. Am J Clin Nutr 2016; 103:851-60. [PMID: 26817504 PMCID: PMC4763492 DOI: 10.3945/ajcn.115.118703] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2015] [Accepted: 12/14/2015] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND There is limited evidence that supports etiologically distinct molecular subtypes of prostate cancer, the identification of which may improve prevention. Given their antioxidant properties, we hypothesized that lycopene and tomato sauce may be especially protective against diseases harboring the common gene fusion transmembrane protease, serine 2 (TMPRSS2):v-ets avian erythroblastosis virus E26 oncogene homolog (ERG). OBJECTIVE We aimed to examine associations between estimated lycopene and tomato sauce intake and the risk of prostate cancer defined by ERG protein expression subtype. DESIGN Our study population consisted of a prospective cohort of 46,719 men from the Health Professionals Follow-Up Study. TMPRSS2:ERG was assessed by ERG immunohistochemistry on tumor tissue microarrays constructed from radical prostatectomy specimens. We used multivariable competing risk models to calculate HRs and 95% CIs for the risk of ERG-positive and, separately, ERG-negative disease. We implemented inverse probability weighting to account for evaluating ERG status only in surgically treated cases. RESULTS During 23 y of follow-up, 5543 men were diagnosed with prostate cancer, among whom 884 were assayed for ERG (426 ERG-positive). With inclusion of only the latter cases, increasing cumulative average tomato sauce intake was associated with a decreased risk of prostate cancer overall (≥2 servings/wk compared with <1 serving/mo; multivariable HR: 0.70; 95% CI: 0.52, 0.95; P-trend = 0.002). With respect to molecular subtypes, cumulative average tomato sauce intake was associated with a decreased risk of ERG-positive disease (HR: 0.54; 95% CI: 0.37, 0.81; P-trend = 0.004) but not with ERG-negative disease (HR: 0.96; 95% CI: 0.62, 1.50; P-trend = 0.10) (P-heterogeneity = 0.04). Increasing quintiles of lycopene intake were associated with a decreased risk of both subtypes (P-heterogeneity = 0.79). Inverse probability weighting did not materially change the results. CONCLUSIONS Our results lend some support to the hypothesis that prostate cancers that harbor TMPRSS2:ERG may be etiologically distinct from fusion-negative cancers. In particular, tomato sauce consumption may play a role in reducing TMPRSS2:ERG-positive disease.
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Affiliation(s)
- Rebecca E Graff
- Departments of Epidemiology, Departments ofEpidemiology and Biostatistics and
| | - Andreas Pettersson
- Departments of Epidemiology, Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Rosina T Lis
- Department of Pathology and Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA
| | | | | | - Kathryn M Wilson
- Departments of Epidemiology, Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Jennifer R Rider
- Departments of Epidemiology, Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Michelangelo Fiorentino
- Departments of Epidemiology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA; Pathology Unit, Addarii Institute, S Orsola-Malpighi Hospital, Bologna, Italy; and
| | - Stephen Finn
- Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA; Department of Histopathology, Trinity College, Dublin, Ireland
| | - Stacey A Kenfield
- Departments of Epidemiology, Urology, University of California, San Francisco, San Francisco, CA; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Massimo Loda
- Department of Pathology and Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA
| | - Edward L Giovannucci
- Departments of Epidemiology, Nutrition, and Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Bernard Rosner
- Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Lorelei A Mucci
- Departments of Epidemiology, Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
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Maru GB, Hudlikar RR, Kumar G, Gandhi K, Mahimkar MB. Understanding the molecular mechanisms of cancer prevention by dietary phytochemicals: From experimental models to clinical trials. World J Biol Chem 2016; 7:88-99. [PMID: 26981198 PMCID: PMC4768127 DOI: 10.4331/wjbc.v7.i1.88] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Revised: 09/04/2015] [Accepted: 11/25/2015] [Indexed: 02/05/2023] Open
Abstract
Chemoprevention is one of the cancer prevention approaches wherein natural/synthetic agent(s) are prescribed with the aim to delay or disrupt multiple pathways and processes involved at multiple steps, i.e., initiation, promotion, and progression of cancer. Amongst environmental chemopreventive compounds, diet/beverage-derived components are under evaluation, because of their long history of exposure to humans, high tolerability, low toxicity, and reported biological activities. This compilation briefly covers and compares the available evidence on chemopreventive efficacy and probable mechanism of chemoprevention by selected dietary phytochemicals (capsaicin, curcumin, diallyl sulphide, genistein, green/black tea polyphenols, indoles, lycopene, phenethyl isocyanate, resveratrol, retinoids and tocopherols) in experimental systems and clinical trials. All the dietary phytochemicals covered in this review have demonstrated chemopreventive efficacy against spontaneous or carcinogen-induced experimental tumors and/or associated biomarkers and processes in rodents at several organ sites. The observed anti-initiating, anti-promoting and anti-progression activity of dietary phytochemicals in carcinogen-induced experimental models involve phytochemical-mediated redox changes, modulation of enzymes and signaling kinases resulting to effects on multiple genes and cell signaling pathways. Results from clinical trials using these compounds have not shown them to be chemopreventive. This may be due to our: (1) inability to reproduce the exposure conditions, i.e., levels, complexity, other host and lifestyle factors; and (2) lack of understanding about the mechanisms of action and agent-mediated toxicity in several organs and physiological processes in the host. Current research efforts in addressing the issues of exposure conditions, bioavailability, toxicity and the mode of action of dietary phytochemicals may help address the reason for observed mismatch that may ultimately lead to identification of new chemopreventive agents for protection against broad spectrum of exposures.
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Bulaj G, Ahern MM, Kuhn A, Judkins ZS, Bowen RC, Chen Y. Incorporating Natural Products, Pharmaceutical Drugs, Self-Care and Digital/Mobile Health Technologies into Molecular-Behavioral Combination Therapies for Chronic Diseases. CURRENT CLINICAL PHARMACOLOGY 2016; 11:128-45. [PMID: 27262323 PMCID: PMC5011401 DOI: 10.2174/1574884711666160603012237] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/03/2016] [Revised: 05/30/2016] [Accepted: 05/31/2016] [Indexed: 02/08/2023]
Abstract
Merging pharmaceutical and digital (mobile health, mHealth) ingredients to create new therapies for chronic diseases offers unique opportunities for natural products such as omega-3 polyunsaturated fatty acids (n-3 PUFA), curcumin, resveratrol, theanine, or α-lipoic acid. These compounds, when combined with pharmaceutical drugs, show improved efficacy and safety in preclinical and clinical studies of epilepsy, neuropathic pain, osteoarthritis, depression, schizophrenia, diabetes and cancer. Their additional clinical benefits include reducing levels of TNFα and other inflammatory cytokines. We describe how pleiotropic natural products can be developed as bioactive incentives within the network pharmacology together with pharmaceutical drugs and self-care interventions. Since approximately 50% of chronically-ill patients do not take pharmaceutical drugs as prescribed, psychobehavioral incentives may appeal to patients at risk for medication non-adherence. For epilepsy, the incentive-based network therapy comprises anticonvulsant drugs, antiseizure natural products (n-3 PUFA, curcumin or/and resveratrol) coupled with disease-specific behavioral interventions delivered by mobile medical apps. The add-on combination of antiseizure natural products and mHealth supports patient empowerment and intrinsic motivation by having a choice in self-care behaviors. The incentivized therapies offer opportunities: (1) to improve clinical efficacy and safety of existing drugs, (2) to catalyze patient-centered, disease self-management and behavior-changing habits, also improving health-related quality-of-life after reaching remission, and (3) merging copyrighted mHealth software with natural products, thus establishing an intellectual property protection of medical treatments comprising the natural products existing in public domain and currently promoted as dietary supplements. Taken together, clinical research on synergies between existing drugs and pleiotropic natural products, and their integration with self-care, music and mHealth, expands precision/personalized medicine strategies for chronic diseases via pharmacological-behavioral combination therapies.
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Affiliation(s)
- Grzegorz Bulaj
- Department of Medicinal Chemistry, College of Pharmacy, Skaggs Pharmacy Institute, University of Utah, 30 South 2000 East, Salt Lake City, Utah 84112, USA.
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Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application. J Nutr Metab 2015; 2015:760689. [PMID: 26167297 PMCID: PMC4488002 DOI: 10.1155/2015/760689] [Citation(s) in RCA: 115] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2015] [Accepted: 03/20/2015] [Indexed: 12/16/2022] Open
Abstract
Research into human biotransformation and elimination systems continues to evolve. Various clinical and in vivo studies have been undertaken to evaluate the effects of foods and food-derived components on the activity of detoxification pathways, including phase I cytochrome P450 enzymes, phase II conjugation enzymes, Nrf2 signaling, and metallothionein. This review summarizes the research in this area to date, highlighting the potential for foods and nutrients to support and/or modulate detoxification functions. Clinical applications to alter detoxification pathway activity and improve patient outcomes are considered, drawing on the growing understanding of the relationship between detoxification functions and different disease states, genetic polymorphisms, and drug-nutrient interactions. Some caution is recommended, however, due to the limitations of current research as well as indications that many nutrients exert biphasic, dose-dependent effects and that genetic polymorphisms may alter outcomes. A whole-foods approach may, therefore, be prudent.
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Magbanua MJM, Wolf DM, Yau C, Davis SE, Crothers J, Au A, Haqq CM, Livasy C, Rugo HS, Esserman L, Park JW, van 't Veer LJ. Serial expression analysis of breast tumors during neoadjuvant chemotherapy reveals changes in cell cycle and immune pathways associated with recurrence and response. Breast Cancer Res 2015; 17:73. [PMID: 26021444 PMCID: PMC4479083 DOI: 10.1186/s13058-015-0582-3] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2015] [Accepted: 05/13/2015] [Indexed: 12/20/2022] Open
Abstract
INTRODUCTION The molecular biology involving neoadjuvant chemotherapy (NAC) response is poorly understood. To elucidate the impact of NAC on the breast cancer transcriptome and its association with clinical outcome, we analyzed gene expression data derived from serial tumor samples of patients with breast cancer who received NAC in the I-SPY 1 TRIAL. METHODS Expression data were collected before treatment (T1), 24-96 hours after initiation of chemotherapy (T2) and at surgery (TS). Expression levels between T1 and T2 (T1 vs. T2; n = 36) and between T1 and TS (T1 vs. TS; n = 39) were compared. Subtype was assigned using the PAM50 gene signature. Differences in early gene expression changes (T2 - T1) between responders and nonresponders, as defined by residual cancer burden, were evaluated. Cox proportional hazards modeling was used to identify genes in residual tumors associated with recurrence-free survival (RFS). Pathway analysis was performed with Ingenuity software. RESULTS When we compared expression profiles at T1 vs. T2 and at T1 vs. TS, we detected significantly altered expression of 150 and 59 transcripts, respectively. We observed notable downregulation of proliferation and immune-related genes at T2. Lower concordance in subtype assignment was observed between T1 and TS (62 %) than between T1 and T2 (75 %). Analysis of early gene expression changes (T2 - T1) revealed that decreased expression of cell cycle inhibitors was associated with poor response. Increased interferon signaling (TS - T1) and high expression of cell proliferation genes in residual tumors (TS) were associated with reduced RFS. CONCLUSIONS Serial gene expression analysis revealed candidate immune and proliferation pathways associated with response and recurrence. Larger studies incorporating the approach described here are warranted to identify predictive and prognostic biomarkers in the NAC setting for specific targeted therapies. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00033397 . Registered 9 Apr 2002.
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Affiliation(s)
- Mark Jesus M Magbanua
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. .,Division of Hematology/Oncology, University of California San Francisco, Box 1387, 2340 Sutter Street, San Francisco, CA, 94115, USA.
| | - Denise M Wolf
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
| | - Christina Yau
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. .,Department of Surgery, University of California San Francisco, San Francisco, CA, USA. .,Buck Institute for Research on Aging, Novato, CA, USA.
| | - Sarah E Davis
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. .,Department of Surgery, University of California San Francisco, San Francisco, CA, USA.
| | - Julia Crothers
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. .,Division of Hematology/Oncology, University of California San Francisco, Box 1387, 2340 Sutter Street, San Francisco, CA, 94115, USA.
| | - Alfred Au
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. .,Department of Surgery, University of California San Francisco, San Francisco, CA, USA.
| | - Christopher M Haqq
- Department of Urology, University of California San Francisco, San Francisco, CA, USA.
| | - Chad Livasy
- UNC Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
| | - Hope S Rugo
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. .,Division of Hematology/Oncology, University of California San Francisco, Box 1387, 2340 Sutter Street, San Francisco, CA, 94115, USA.
| | | | - Laura Esserman
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. .,Department of Surgery, University of California San Francisco, San Francisco, CA, USA.
| | - John W Park
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. .,Division of Hematology/Oncology, University of California San Francisco, Box 1387, 2340 Sutter Street, San Francisco, CA, 94115, USA.
| | - Laura J van 't Veer
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. .,Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
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Linnewiel-Hermoni K, Khanin M, Danilenko M, Zango G, Amosi Y, Levy J, Sharoni Y. The anti-cancer effects of carotenoids and other phytonutrients resides in their combined activity. Arch Biochem Biophys 2015; 572:28-35. [DOI: 10.1016/j.abb.2015.02.018] [Citation(s) in RCA: 81] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2014] [Revised: 02/11/2015] [Accepted: 02/12/2015] [Indexed: 12/24/2022]
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de Roos B, Duthie GG. Role of dietary pro-oxidants in the maintenance of health and resilience to oxidative stress. Mol Nutr Food Res 2015; 59:1229-48. [PMID: 25546122 DOI: 10.1002/mnfr.201400568] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2014] [Revised: 11/26/2014] [Accepted: 11/27/2014] [Indexed: 12/20/2022]
Abstract
The average length of human life is increasing, but so does the incidence of age- and lifestyle-related diseases. Improving diet and lifestyle is a key strategy for lifelong health and underlying mechanisms may well include increasing resilience pathways. The purpose of this review is to highlight and evaluate novel mechanisms by which dietary pro-oxidants, including bioactive phytochemicals and fatty acids, increase reactive oxygen species (ROS) concentrations just enough to activate transcription factor activation of nuclear factor erythroid 2 related factor 2 (Nrf-2) and heat shock factor (HSF), leading to an increase in levels of antioxidant enzymes and heat shock proteins that protect against the damaging effects of ROS. An increasing number of in vivo studies have now shown that dietary pro-oxidant compounds can increase the production of such resilience products. In most studies, dietary pro-oxidants normalized levels of antioxidant enzymes that were decreased by a range of different challenges, rather than raising levels of resilience products per se. Also, it is important to consider that the antioxidant response can be different for different organs. For future studies, however, the measurement of resilience markers may significantly improve our ability to prove the efficacy by which dietary bioactives with pro-oxidant capacities improve lifelong health.
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Affiliation(s)
- Baukje de Roos
- Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK
| | - Garry G Duthie
- Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK
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Wan L, Tan HL, Thomas-Ahner JM, Pearl DK, Erdman JW, Moran NE, Clinton SK. Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis. Cancer Prev Res (Phila) 2014; 7:1228-39. [PMID: 25315431 DOI: 10.1158/1940-6207.capr-14-0182] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Consumption of tomato products containing the carotenoid lycopene is associated with a reduced risk of prostate cancer. To identify gene expression patterns associated with early testosterone-driven prostate carcinogenesis, which are impacted by dietary tomato and lycopene, wild-type (WT) and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed control or tomato- or lycopene-containing diets from 4 to 10 weeks of age. Eight-week-old mice underwent sham surgery, castration, or castration followed by testosterone repletion (2.5 mg/kg/d initiated 1 week after castration). Ten-week-old intact TRAMP mice exhibit early multifocal prostatic intraepithelial neoplasia. Of the 200 prostate cancer-related genes measured by quantitative NanoString, 189 are detectable, 164 significantly differ by genotype, 179 by testosterone status, and 30 by diet type (P < 0.05). In TRAMP, expression of Birc5, Mki67, Aurkb, Ccnb2, Foxm1, and Ccne2 is greater compared with WT and is decreased by castration. In parallel, castration reduces Ki67-positive staining (P < 0.0001) compared with intact and testosterone-repleted TRAMP mice. Expression of genes involved in androgen metabolism/signaling pathways is reduced by lycopene feeding (Srd5a1) and by tomato feeding (Srd5a2, Pxn, and Srebf1). In addition, tomato feeding significantly reduced expression of genes associated with stem cell features, Aldh1a and Ly6a, whereas lycopene feeding significantly reduced expression of neuroendocrine differentiation-related genes, Ngfr and Syp. Collectively, these studies demonstrate a profile of testosterone-regulated genes associated with early prostate carcinogenesis that are potential mechanistic targets of dietary tomato components. Future studies on androgen signaling/metabolism, stem cell features, and neuroendocrine differentiation pathways may elucidate the mechanisms by which dietary tomato and lycopene impact prostate cancer risk.
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Affiliation(s)
- Lei Wan
- Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Interdisciplinary Nutrition Program, The Ohio State University, Columbus, Ohio
| | - Hsueh-Li Tan
- Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Interdisciplinary Nutrition Program, The Ohio State University, Columbus, Ohio
| | | | - Dennis K Pearl
- Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Department of Statistics, The Ohio State University, Columbus, Ohio
| | - John W Erdman
- Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois
| | - Nancy E Moran
- Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio
| | - Steven K Clinton
- Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
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Moreel X, Allaire J, Léger C, Caron A, Labonté MÈ, Lamarche B, Julien P, Desmeules P, Têtu B, Fradet V. Prostatic and dietary omega-3 fatty acids and prostate cancer progression during active surveillance. Cancer Prev Res (Phila) 2014; 7:766-76. [PMID: 24824038 DOI: 10.1158/1940-6207.capr-13-0349] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The association between omega-3 (ω-3) fatty acids and prostate cancer has been widely studied. However, little is known about the impact of prostate tissue fatty acid content on prostate cancer progression. We hypothesized that compared with the estimated dietary ω-3 fatty acids intake and the ω-3 fatty acids levels measured in red blood cells (RBC), the prostate tissue ω-3 fatty acid content is more strongly related to prostate cancer progression. We present the initial observations from baseline data of a phase II clinical trial conducted in a cohort of 48 untreated men affected with low-risk prostate cancer, managed under active surveillance. These men underwent a first repeat biopsy session within 6 months after the initial diagnosis of low-risk prostate cancer, at which time 29% of the men had progressed from a Gleason score of 6 to a Gleason score of 7. At the first repeat biopsy session, fatty acid levels were assessed with a food-frequency questionnaire, and determined in the RBC and in the prostate tissue biopsy. We found that eicosapentaenoic acid (EPA) was associated with a reduced risk of prostate cancer progression when measured directly in the prostate tissue. Thus, this initial interim study analysis suggests that prostate tissue ω-3 fatty acids, especially EPA, may be protective against prostate cancer progression in men with low-risk prostate cancer.
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Affiliation(s)
- Xavier Moreel
- Authors' Affiliations: Department of Surgery (Urology), CHU de Québec-L'Hôtel-Dieu de Quebec, Quebec, Canada and CHU de Quebec Research Center, Oncology Axis, Laval University, Quebec, Canada
| | - Janie Allaire
- Authors' Affiliations: Department of Surgery (Urology), CHU de Québec-L'Hôtel-Dieu de Quebec, Quebec, Canada and CHU de Quebec Research Center, Oncology Axis, Laval University, Quebec, Canada
| | - Caroline Léger
- Authors' Affiliations: Department of Surgery (Urology), CHU de Québec-L'Hôtel-Dieu de Quebec, Quebec, Canada and CHU de Quebec Research Center, Oncology Axis, Laval University, Quebec, Canada
| | - André Caron
- Authors' Affiliations: Department of Surgery (Urology), CHU de Québec-L'Hôtel-Dieu de Quebec, Quebec, Canada and CHU de Quebec Research Center, Oncology Axis, Laval University, Quebec, Canada
| | - Marie-Ève Labonté
- Institute of Nutrition and Functional Foods, Laval University, Quebec, Canada
| | - Benoît Lamarche
- Institute of Nutrition and Functional Foods, Laval University, Quebec, Canada
| | - Pierre Julien
- CHU de Quebec Research Center, Endocrinology and Nephrology Axis, Laval University, Quebec, Canada; and
| | - Patrice Desmeules
- Department of Pathology, CHU de Quebec-Hôpital Saint-Sacrement, Quebec, Canada and CHU de Quebec Research Center, Oncology Axis, Laval University, Quebec, Canada
| | - Bernard Têtu
- Department of Pathology, CHU de Quebec-Hôpital Saint-Sacrement, Quebec, Canada and CHU de Quebec Research Center, Oncology Axis, Laval University, Quebec, Canada
| | - Vincent Fradet
- Authors' Affiliations: Department of Surgery (Urology), CHU de Québec-L'Hôtel-Dieu de Quebec, Quebec, Canada and CHU de Quebec Research Center, Oncology Axis, Laval University, Quebec, Canada; Institute of Nutrition and Functional Foods, Laval University, Quebec, Canada;
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Camp KM, Trujillo E. Position of the Academy of Nutrition and Dietetics: nutritional genomics. J Acad Nutr Diet 2014; 114:299-312. [PMID: 24439821 DOI: 10.1016/j.jand.2013.12.001] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Indexed: 01/28/2023]
Abstract
It is the position of the Academy of Nutrition and Dietetics that nutritional genomics provides insight into how diet and genotype interactions affect phenotype. The practical application of nutritional genomics for complex chronic disease is an emerging science and the use of nutrigenetic testing to provide dietary advice is not ready for routine dietetics practice. Registered dietitian nutritionists need basic competency in genetics as a foundation for understanding nutritional genomics; proficiency requires advanced knowledge and skills. Unlike single-gene defects in which a mutation in a single gene results in a specific disorder, most chronic diseases, such as cardiovascular disease, diabetes, and cancer are multigenetic and multifactorial and therefore genetic mutations are only partially predictive of disease risk. Family history, biochemical parameters, and the presence of risk factors in individuals are relevant tools for personalizing dietary interventions. Direct-to-consumer genetic testing is not closely regulated in the United States and may not be accompanied by access to health care practitioners. Applying nutritional genomics in clinical practice through the use of genetic testing requires that registered dietitian nutritionists understand, interpret, and communicate complex test results in which the actual risk of developing a disease may not be known. The practical application of nutritional genomics in dietetics practice will require an evidence-based approach to validate that personalized recommendations result in health benefits to individuals and do not cause harm.
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Magbanua MJM, Richman EL, Sosa EV, Jones LW, Simko J, Shinohara K, Haqq CM, Carroll PR, Chan JM. Physical activity and prostate gene expression in men with low-risk prostate cancer. Cancer Causes Control 2014; 25:515-23. [PMID: 24504435 DOI: 10.1007/s10552-014-0354-x] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2013] [Accepted: 01/28/2014] [Indexed: 12/17/2022]
Abstract
PURPOSE Vigorous physical activity after diagnosis of localized prostate cancer may reduce the risk of disease progression and prostate cancer-specific mortality. The molecular mechanisms by which physical activity may exert protective effects in the prostate remain unknown. METHODS We examined the associations between self-reported physical activity and gene expression patterns in morphologically normal prostate tissue of 71 men with low-risk prostate cancer on active surveillance. Differential gene expression, gene set, and pathway analyses were conducted comparing dichotomous groups defined by type, intensity, and amount of physical activity reported. RESULTS Cell cycling and DNA repair pathways were up-regulated in men who participated in ≥ 3 h/week vigorous activity compared with men who did not. In addition, canonical pathways involved in cell signaling and metabolism, the cellular effects of sildenafil (Viagra), and the Nrf2-mediated oxidative stress response were modulated in men who reported ≥ 3 h/week of vigorous activity. Differential expression analysis at the individual gene level revealed modest differences between men who performed vigorous activity for ≥ 3 h/week and those who did not. There were no differences in prostate gene expression in comparisons with exercise groupings that did not consider both duration and intensity of activity. CONCLUSIONS Prostate gene expression and pathway analyses revealed sets of transcripts that may be modulated in normal prostate tissue by participating in ≥ 3 h/week of vigorous activity after diagnosis of low-risk prostate cancer. These findings suggest potential biological mechanisms by which vigorous activity may reduce risk of prostate cancer progression and warrant further study and validation.
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Affiliation(s)
- Mark Jesus M Magbanua
- Division of Hematology/Oncology, University of California San Francisco, San Francisco, CA, USA
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Antineuroinflammatory effects of lycopene via activation of adenosine monophosphate-activated protein kinase-α1/heme oxygenase-1 pathways. Neurobiol Aging 2014; 35:191-202. [DOI: 10.1016/j.neurobiolaging.2013.06.020] [Citation(s) in RCA: 86] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2012] [Revised: 05/21/2013] [Accepted: 06/30/2013] [Indexed: 12/21/2022]
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An appraisal of the therapeutic value of lycopene for the chemoprevention of prostate cancer: A nutrigenomic approach. Food Res Int 2013. [DOI: 10.1016/j.foodres.2013.03.027] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Ornish D, Lin J, Chan JM, Epel E, Kemp C, Weidner G, Marlin R, Frenda SJ, Magbanua MJM, Daubenmier J, Estay I, Hills NK, Chainani-Wu N, Carroll PR, Blackburn EH. Effect of comprehensive lifestyle changes on telomerase activity and telomere length in men with biopsy-proven low-risk prostate cancer: 5-year follow-up of a descriptive pilot study. Lancet Oncol 2013; 14:1112-1120. [PMID: 24051140 DOI: 10.1016/s1470-2045(13)70366-8] [Citation(s) in RCA: 247] [Impact Index Per Article: 20.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Azrad M, Turgeon C, Demark-Wahnefried W. Current evidence linking polyunsaturated Fatty acids with cancer risk and progression. Front Oncol 2013; 3:224. [PMID: 24027672 PMCID: PMC3761560 DOI: 10.3389/fonc.2013.00224] [Citation(s) in RCA: 125] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2013] [Accepted: 08/15/2013] [Indexed: 12/14/2022] Open
Abstract
There is increasing evidence that polyunsaturated fatty acids (PUFAs) play a role in cancer risk and progression. The n-3 family of PUFAs includes alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) while the n-6 family includes linolenic acid (LA) and arachidonic acid (AA). EPA and DHA are precursors for anti-inflammatory lipid mediators while AA is a precursor for pro-inflammatory lipid mediators. Collectively, PUFAs play crucial roles in maintaining cellular homeostasis, and perturbations in dietary intake or PUFA metabolism could result in cellular dysfunction and contribute to cancer risk and progression. Epidemiologic studies provide an inconsistent picture of the associations between dietary PUFAs and cancer. This discrepancy may reflect the difficulties in collecting accurate dietary data; however, it also may reflect genetic variation in PUFA metabolism which has been shown to modify physiological levels of PUFAs and cancer risk. Also, host-specific mutations as a result of cellular transformation could modify metabolism of PUFAs in the target-tissue. Clinical trials have shown that supplementation with PUFAs or foods high in PUFAs can affect markers of inflammation, immune function, tumor biology, and prognosis. Pre-clinical investigations have begun to elucidate how PUFAs may mediate cell proliferation, apoptosis and angiogenesis, and the signaling pathways involved in these processes. The purpose of this review is to summarize the current evidence linking PUFAs and their metabolites with cancer and the molecular mechanisms that underlie this association. Identifying the molecular mechanism(s) through which PUFAs affect cancer risk and progression will provide an opportunity to pursue focused dietary interventions that could translate into the development of personalized diets for cancer control.
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Affiliation(s)
- Maria Azrad
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Chelsea Turgeon
- School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Wendy Demark-Wahnefried
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
- Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA
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Eigl B, Gleave M, Chi K. The Future of Systemic Therapies for Localised Prostate Cancer. Clin Oncol (R Coll Radiol) 2013; 25:506-13. [DOI: 10.1016/j.clon.2013.04.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2013] [Revised: 03/15/2013] [Accepted: 04/10/2013] [Indexed: 01/16/2023]
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The omega-3 polyunsaturated fatty acid DHA induces simultaneous apoptosis and autophagy via mitochondrial ROS-mediated Akt-mTOR signaling in prostate cancer cells expressing mutant p53. BIOMED RESEARCH INTERNATIONAL 2013; 2013:568671. [PMID: 23841076 PMCID: PMC3691929 DOI: 10.1155/2013/568671] [Citation(s) in RCA: 122] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/12/2013] [Accepted: 04/29/2013] [Indexed: 11/17/2022]
Abstract
Docosahexaenoic acid (DHA) induces autophagy-associated apoptotic cell death in wild-type p53 cancer cells via regulation of p53. The present study investigated the effects of DHA on PC3 and DU145 prostate cancer cell lines harboring mutant p53. Results show that, in addition to apoptosis, DHA increased the expression levels of lipidated form LC3B and potently stimulated the autophagic flux, suggesting that DHA induces both autophagy and apoptosis in cancer cells expressing mutant p53. DHA led to the generation of mitochondrial reactive oxygen species (ROS), as shown by the mitochondrial ROS-specific probe mitoSOX. Similarly, pretreatment with the antioxidant N-acetyl-cysteine (NAC) markedly inhibited both the autophagy and the apoptosis triggered by DHA, indicating that mitochondrial ROS mediate the cytotoxicity of DHA in mutant p53 cells. Further, DHA reduced the levels of phospho-Akt and phospho-mTOR in a concentration-dependent manner, while NAC almost completely blocked that effect. Collectively, these findings present a novel mechanism of ROS-regulated apoptosis and autophagy that involves Akt-mTOR signaling in prostate cancer cells with mutant p53 exposed to DHA.
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Mechanisms of omega-3 polyunsaturated fatty acids in prostate cancer prevention. BIOMED RESEARCH INTERNATIONAL 2013; 2013:824563. [PMID: 23762859 PMCID: PMC3676993 DOI: 10.1155/2013/824563] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/06/2013] [Revised: 05/02/2013] [Accepted: 05/08/2013] [Indexed: 12/22/2022]
Abstract
This review focuses on several key areas where progress has been made recently to highlight the role of omega-3 polyunsaturated fatty acid in prostate cancer prevention.
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Nguyen TTT, Shaw PN, Parat MO, Hewavitharana AK. Anticancer activity ofCarica papaya: A review. Mol Nutr Food Res 2012; 57:153-64. [DOI: 10.1002/mnfr.201200388] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2012] [Revised: 09/16/2012] [Accepted: 10/09/2012] [Indexed: 12/20/2022]
Affiliation(s)
- Thao T. T. Nguyen
- School of Pharmacy,; The University of Queensland; Brisbane; Australia
| | - Paul N. Shaw
- School of Pharmacy,; The University of Queensland; Brisbane; Australia
| | - Marie-Odile Parat
- School of Pharmacy,; The University of Queensland; Brisbane; Australia
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Abstract
Personalized nutrition has been traditionally based on the adjustment of food and diet according to individual needs and preferences. At present, this concept is being reinforced through the application of state-of-the-art high-throughput technologies to help understand the molecular mechanisms underlying a healthy state. This knowledge could enable the adjustment of general dietary recommendations to match the needs of specific population groups based on their molecular profiles. The optimal development of evidence-based nutritional guidance to promote health requires an adequate assessment of nutrient bioavailability, bioactivity, and bioefficacy. To achieve this, reliable information about exposure to nutrients, their intake, and functional effects is required; thus, the identification of valid biomarkers using standardized analytical procedures is necessary. Although some nutritional biomarkers are now successfully used (eg, serum retinol, zinc, ferritin, and folate), a comprehensive set to assess the nutritional status and metabolic conditions of nutritional relevance is not yet available. Also, there is very limited knowledge on how the extensive human genetic variability influences the interpretation of these biomarkers. In this context, nutrigenomics seems to be a promising approach to identify new biomarkers in nutrition, through an integrative application of transcriptomics, proteomics, metabolomics, epigenomics, and nutrigenetics in human nutritional research.
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Marthick JR, Dickinson JL. Emerging putative biomarkers: the role of alpha 2 and 6 integrins in susceptibility, treatment, and prognosis. Prostate Cancer 2012; 2012:298732. [PMID: 22900191 PMCID: PMC3415072 DOI: 10.1155/2012/298732] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2012] [Accepted: 05/17/2012] [Indexed: 11/22/2022] Open
Abstract
The genetic architecture underpinning prostate cancer is complex, polygenic and despite recent significant advances many questions remain. Advances in genetic technologies have greatly improved our ability to identify genetic variants associated with complex disease including prostate cancer. Genome-wide association studies (GWASs) and microarray gene expression studies have identified genetic associations with prostate cancer susceptibility and tumour development. The integrins feature prominently in both studies examining the underlying genetic susceptibility and mechanisms driving prostate tumour development. Integrins are cell adhesion molecules involved in extracellular and intracellular signalling and are imperative for tumour development, migration, and angiogenesis. Although several integrins have been implicated in tumour development, the roles of integrin α(2) and integrin α(6) are the focus of this paper as evidence is now emerging that these integrins are implicit in prostate cancer susceptibility, cancer stem cell biology, angiogenesis, cell migration, and metastases to bone and represent potential biomarkers and therapeutic targets. There currently exists an urgent need to develop tools that differentiate indolent from aggressive prostate cancers and predict how patients will respond to treatment. This paper outlines the evidence supporting the use of α(2) and α(6) integrins in clinical applications for tailored patient treatment.
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Affiliation(s)
- James R. Marthick
- Menzies Research Institute Tasmania, University of Tasmania, 17 Liverpool Street Hobart, TAS 7000, Australia
| | - Joanne L. Dickinson
- Menzies Research Institute Tasmania, University of Tasmania, 17 Liverpool Street Hobart, TAS 7000, Australia
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