Impact of Glucosinolates Intervention in Controlling the Progression of Cancer: A Systematic Review of a Randomized Controlled Trial
Main Article Content
Abstract
Introduction: Glucosinolates (GSLs) are sulfur and nitrogen-containing compounds in the Brassicaceae family of eudicots, such as mustard, broccoli and cabbage. GSLs are potent secondary metabolites that protect plants against environmental stressors, particularly herbivores and pathogens. In recent years, increasing attention has been directed towards the potential of bioactive compounds derived from natural sources as adjunctive strategies in cancer prevention and control. GSLs have emerged as promising candidates due to their physiological effects and anticancer properties. Objective: This systematic review aims to explain the significance of GSLs and their derivatives intervention on cancer progression through a systematic review of randomized controlled trials (RCTs). Materials and methods: Four electronic databases were used in this study: PubMed, Scopus, Web of Science (WoS) and Science Direct. Twenty-one RCTs were selected based on several inclusion and exclusion criteria. Selection of the studies, data extraction, and quality evaluation were carried out separately by two reviewers. Results: The contribution to the current knowledge on the effectiveness of GSLs in controlling cancer progression and prevention is highlighted from the analysis of the selected 21 clinical trial articles. These trials were conducted using GSLs as a single agent or combined with other therapeutic agents against various cancers. Aliphatic GSLs, indolic GSLs and isothiocyanate derivatives are used as interventions in the studies. Conclusion: This review supports the need for more studies on the pharmacological and biological properties of GSLs in different types of cancer to be conducted to understand how GSLs can help in controlling the progression of cancer towards its prevention.
Downloads
Article Details
References
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. doi: 10.3322/caac.21492.
Fitzmaurice C, Abate D, Abbasi N, Abbastabar H, Abd-Allah F, Abdel-Rahman O, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-Adjusted life-years for 29 cancer groups, 1990 to 2017: A systematic analysis for the global burden of disease study. JAMA Oncol. 2019;5(12):1749–68. doi: 10.1001/jamaoncol.2019.2996.
Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin. 2019;69(5):363–85. doi: 10.3322/caac.21565.
Afrin S, Giampieri F, Gasparrini M, Forbes-Hernández TY, Cianciosi D, Reboredo-Rodriguez P, et al. Dietary phytochemicals in colorectal cancer prevention and treatment: A focus on the molecular mechanisms involved. Biotechnology Advances. 2020; 38:107322. doi: 10.1016/j.biotechadv.2018.11.011.
Edwards IR, Aronson JK. Adverse drug reactions: Definitions, diagnosis, and management. Lancet. 2000;356(9237):1255–9. doi: 10.1016/S0140-6736(00)02799-9.
Soundararajan P, Kim JS. Anti-carcinogenic glucosinolates in cruciferous vegetables and their antagonistic effects on prevention of cancers. Molecules. 2018;23. doi: 10.3390/molecules23112983.
Pan L, Chai HB, Kinghorn AD. Discovery of new anticancer agents from higher plants. Frontiers in Bioscience. 2012;4 S(1):142–56. doi: 10.2741/257.
Fakhri S, Moradi SZ, Farzaei MH, Bishayee A, Rameeh V, Chamovitz DA, et al. Brassicaceae-derived anticancer agents: Towards a green approach to beat cancer. Molecules. 2020;12(1):1–15. doi: 10.1007/s10886-016-0760-5.
Majolo F, de Oliveira Becker Delwing LK, Marmitt DJ, Bustamante-Filho IC, Goettert MI. Medicinal plants and bioactive natural compounds for cancer treatment: Important advances for drug discovery. Phytochem Lett. 2019;31:196–207. doi: /10.1016/j.phytol.2019.04.003.
Kuran D, Pogorzelska A, Wiktorska K. Breast Cancer Prevention-Is there a Future for Sulforaphane and Its Analogs? Nutrients. 2020;12(6). doi: 10.3390/nu12061559.
Fontana F, Raimondi M, Marzagalli M, Di Domizio A, Limonta P. Natural Compounds in Prostate Cancer Prevention and Treatment: Mechanisms of Action and Molecular Targets. Cells. 2020;9(2):460. doi: 10.3390/cells9020460.
Ijaz S, Akhtar N, Khan MS, Hameed A, Irfan M, Arshad MA, et al. Plant derived anticancer agents: A green approach towards skin cancers. Biomedicine and Pharmacotherapy. 2018;103:1643-51. doi: 10.1016/j.biopha.2018.04.113.
De Sousa Monteiro L, Bastos KX, Barbosa-Filho JM, De Athayde-Filho PF, De Fátima Formiga Melo Diniz M, Sobral MV. Medicinal plants and other living organisms with antitumor potential against lung cancer. Evidence-based Complementary and Alternative Medicine. 2014;604152. doi: 10.1155/2014/604152.
Clay NK, Adio AM, Denoux C, Jander G, Ausubel FM. Glucosinolate Metabolites Required for an Arabidopsis Innate Immune Response. Science. 2009;323:95–101. doi: 10.1126/science.1164627.
Fahey JW, Zalcmann AT, Talalay P. The chemical diversity and distribution of glucosinolates and isothiocyanates among plants. Phytochemistry. 2001;56:5–51. doi: 10.1016/S0031-9422(00)00316-2.
Reichelt M, Brown PD, Schneider B, Oldham NJ, Stauber E, Tokuhisa J, et al. Benzoic acid glucosinolate esters and other glucosinolates from Arabidopsis thaliana. Phytochemistry. 2002;59:663–71. doi: 10.1016/s0031-9422(02)00014-6.
Chhajed S, Misra BB, Tello N, Chen S. Chemodiversity of the glucosinolate-myrosinase system at the single cell type resolution. Front Plant Sci. 2019;10:618. doi: 10.3389/fpls.2019.00618.
Petersen A, Wang C, Crocoll C, Halkier BA. Biotechnological approaches in glucosinolate production. J Integr Plant Biol. 2018;60(12):1231–48. doi: 10.1111/jipb.12705.
Bell L. The Biosynthesis of Glucosinolates: Insights, Inconsistencies, and Unknowns. Annual Plant Reviews. 2019;2(3):1–31. doi: 10.1002/9781119312994.apr0708.
Harun S, Abdullah-Zawawi MR, Goh HH, Mohamed-Hussein ZA. A Comprehensive Gene Inventory for Glucosinolate Biosynthetic Pathway in Arabidopsis thaliana. J Agric Food Chem. 2020;68(28):7281–97. doi: 10.1021/acs.jafc.0c01916.
Blažević I, Montaut S, Burčul F, Olsen CE, Burow M, Rollin P, et al. Glucosinolate structural diversity, identification, chemical synthesis and metabolism in plants. Phytochemistry. 2020;169:112100. doi: 10.1016/j.phytochem.2019.112100.
Barba FJ, Nikmaram N, Roohinejad S, Khelfa A, Zhu Z, Koubaa M. Bioavailability of Glucosinolates and Their Breakdown Products: Impact of Processing. Front Nutr. 2016;3:24. doi: 10.3389/fnut.2016.00024.
Seo MS, Kim JS. Understanding of MYB transcription factors involved in glucosinolate biosynthesis in Brassicaceae. Molecules. 2017;22(9):1549. doi: 10.3390/molecules22091549.
Koroleva OA, Cramer R. Single-cell proteomic analysis of glucosinolate-rich S-cells in Arabidopsis thaliana. Methods. 2011;54(4):413-23. doi: 10.1016/j.ymeth.2011.06.005.
Sugiyama R, Hirai MY. Atypical Myrosinase as a Mediator of Glucosinolate Functions in Plants. Vol. 10, Frontiers in Plant Science. 2019;10:1008. doi: 10.3389/fpls.2019.01008.
Herr I, Büchler MW. Dietary constituents of broccoli and other cruciferous vegetables : Implications for prevention and therapy of cancer. Cancer Treat Rev. 2010;36(5):377–83. doi: 10.1016/j.ctrv.2010.01.002.
Yu P, Yu L, Lu Y. Dietary consumption of cruciferous vegetables and bladder cancer risk: A systematic review and meta-analysis. Front Nutr. 2022;9:944451. doi: 10.3389/fnut.2022.944451.
Nandini DB, Rao RS, Deepak BS, Reddy PB. Sulforaphane in broccoli: The green chemoprevention!! Role in cancer prevention and therapy. Journal of Oral and Maxillofacial Pathology. 2020;24(2):405. doi: 10.4103/jomfp.JOMFP_126_19.
Jiang X, Liu Y, Ma L, Ji R, Qu Y, Xin Y, et al. Chemopreventive activity of sulforaphane. Drug Des Devel Ther. 2018;12:2905-13. doi: 10.2147/DDDT.S100534.
Wang XF, Wu DM, Li BX, Lu YJ, Yang BF. Synergistic inhibitory effect of sulforaphane and 5-fluorouracil in high and low metastasis cell lines of salivary gland adenoid cystic carcinoma. Phytotherapy research. 2009;23(3):303-7. doi: 10.1002/ptr.2618.
Sailo BL, Liu L, Chauhan S, Girisa S, Hegde M, Liang L, et al. Harnessing Sulforaphane Potential as a Chemosensitizing Agent: A Comprehensive Review. Cancers. 2024;16(2):244. doi: 10.3390/cancers16020244.
Reyes-Hernández OD, Figueroa-González G, Quintas-Granados LI, Gutiérrez-Ruíz SC, Hernández-Parra H, Romero-Montero A, et al. 3,3′-Diindolylmethane and indole-3-carbinol: potential therapeutic molecules for cancer chemoprevention and treatment via regulating cellular signaling pathways. Cancer Cell International. 2023;23:180. doi: 10.1186/s12935-023-03031-4.
Williams DE. Indoles Derived From Glucobrassicin: Cancer Chemoprevention by Indole-3-Carbinol and 3,3’-Diindolylmethane. Front Nutr. 2021;8:734334. doi: 10.3389/fnut.2021.734334.
Leem SH, Li XJ, Park MH, Park BH, Kim SM. Genome-wide transcriptome analysis reveals inactivation of Wnt/β-catenin by 3,3’-diindolylmethane inhibiting proliferation of colon cancer cells. Int J Oncol. 2015;47(3):918–26. doi: 10.3892/ijo.2015.3089.
Gao X, Liu J, Cho KB, Kedika S, Guo B. Chemopreventive Agent 3,3′-Diindolylmethane Inhibits MDM2 in Colorectal Cancer Cells. Int J Mol Sci. 2020;21(13):1–13. doi: 10.3390/ijms21134642.
Rogan EG. The Natural Chemopreventive Compound Indole-3-carbinol: State of the Science. In Vivo (Brooklyn). 2006;20(2):221–8. https://iv.iiarjournals.org/content/20/2/221.
Dash R, Hosen SMZ, Karim MR, Kabir MSH, Hossain MM, Junaid M, et al. In silico analysis of indole-3-carbinol and its metabolite DIM as EGFR tyrosine kinase inhibitors in platinum resistant ovarian cancer vis a vis ADME/T property analysis. J Appl Pharm Sci. 2015;5(11):073–8. doi: 10.7324/JAPS.2015.501112.
Weng JR, Tsai CH, Kulp SK, Chen CS. Indole-3-carbinol as a chemopreventive and anti-cancer agent. Cancer Lett. 2008;262(2):153–63. doi: 10.1016/j.canlet.2008.01.033.
Kaur P, Shorey LE, Ho E, Dashwood RH, Williams DE. The epigenome as a potential mediator of cancer and disease prevention in prenatal development. Nutr Rev. 2013;71(7):441–57. doi:10.1111/nure.12030.
Watson G, Beaver L, Williams D, Dashwood R, Ho E. Phytochemicals from Cruciferous Vegetables, Epigenetics, and Prostate Cancer Prevention. AAPS J. 2013;15(4):951. doi: 10.1208/s12248-013-9504-4.
Tang Y, Naito S, Abe-Kanoh N, Ogawa S, Yamaguchi S, Zhu B, et al. Benzyl isothiocyanate attenuates the hydrogen peroxide-induced interleukin-13 expression through glutathione S-transferase P induction in T lymphocytic leukemia cells. J Biochem Mol Toxicol. 2018;32(6):e22054. doi: 10.1002/jbt.22054.
Ibrahim A, Al-Hizab FA, Abushouk AI, Abdel-Daim MM. Nephroprotective Effects of Benzyl Isothiocyanate and Resveratrol Against Cisplatin-Induced Oxidative Stress and Inflammation. Front Pharmacol. 2018;9. doi: 10.3389/fphar.2018.01268.
Romeo L, Iori R, Rollin P, Bramanti P, Mazzon E. Isothiocyanates: An Overview of Their Antimicrobial Activity against Human Infections. Molecules. 2018;23(3):624. doi: 10.3390/molecules23030624.
Dinh TN, Parat MO, Ong YS, Khaw KY. Anticancer activities of dietary benzyl isothiocyanate: A comprehensive review. Pharmacol Res. 2021;169:105666. doi: 10.1016/j.phrs.2021.10566.
Miyoshi N, Takabayashi S, Osawa T, Nakamura Y. Benzyl isothiocyanate inhibits excessive superoxide generation in inflammatory leukocytes: implication for prevention against inflammation-related carcinogenesis. Carcinogenesis. 2004;25(4):567–75. doi: 10.1093/carcin/bgh051.
Morse MA, Zu H, Galati AJ, Schmidt CJ, Stoner GD. Dose-related inhibition by dietary phenethyl isothiocyanate of esophageal tumorigenesis and DNA methylation induced by N-nitrosomethylbenzylamine in rats. Cancer Lett. 1993;72(1–2):103–10. doi: 10.1016/0304-3835(93)90018-5.
Lee Y, Kim YJ, Choi YJ, Lee JW, Lee S, Chung HW. Enhancement of cisplatin cytotoxicity by benzyl isothiocyanate in HL-60 cells. Food and Chemical Toxicology. 2012;50(7):2397–406. doi: 10.1016/j.fct.2012.04.014.
Barton S. Which clinical studies provide the best evidence? : The best RCT still trumps the best observational study. BMJ. 2000;321(7256):255-6. doi: 10.1136/bmj.321.7256.255.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339(7716):332–6. doi: 10.1136/bmj.b2535.
Uman LS. Systematic Reviews and Meta-Analyses. Journal of the Canadian Academy of Child and Adolescent Psychiatry. 2011;20(1):57. https://pmc/articles/PMC3024725/.
Booth A. Unpacking your literature search toolbox: on search styles and tactics. Health Info Libr J. 2008;25(4):313–7. doi: 10.1111/j.1471-1842.2008.00825.x.
Ma LL, Wang YY, Yang ZH, Huang D, Weng H, Zeng XT. Methodological quality (risk of bias) assessment tools for primary and secondary medical studies: What are they and which is better? Mil Med Res. 2020;7(1):1–11. doi: 10.1186/s40779-020-00238-8.
Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366. doi: 10.1136/bmj.l4898.
Bell MC, Crowley-Nowick P, Bradlow HL, Sepkovic DW, Schmidt-Grimminger D, Howell P, et al. Placebo-Controlled Trial of Indole-3-Carbinol in the Treatment of CIN. Gynecol Oncol. 2000;78(2):123–9. doi: 10.1006/gyno.2000.5847.
Chen JG, Johnson J, Egner P, Ng D, Zhu J, Wang JB, et al. Dose-dependent detoxication of the airborne pollutant benzene in a randomized trial of broccoli sprout beverage in Qidong, China. Am J Clin Nutr. 2019;110(3):675–84. doi: 10.1093/ajcn/nqz122.
Traka MH, Melchini A, Coode-Bate J, Kadhi O Al, Saha S, Defernez M, et al. Transcriptional changes in prostate of men on active surveillance after a 12-mo glucoraphanin-rich broccoli intervention-results from the Effect of Sulforaphane on prostate CAncer PrEvention (ESCAPE) randomized controlled trial. Am J Clin Nutr. 2019;109(4):1133–44. doi: 10.1093/ajcn/nqz012.
Kensler TW, Ng D, Carmella SG, Chen M, Jacobson LP, Muñoz A, et al. Modulation of the metabolism of airborne pollutants by glucoraphanin-rich and sulforaphane-rich broccoli sprout beverages in Qidong, China. Carcinogenesis. 2012;33(1):101–7. doi: 10.1093/carcin/bgr229.
Nijhoff WA, Grubben MJAL, Nagengast FM, Jansen JBMJ, Verhagen H, Vanpoppel G, et al. Effects of consumption of Brussels sprouts on intestinal and lymphocytic glutathione S-transferases in humans. Carcinogenesis. 1995;16(9):2125–8. doi: 10.1093/carcin/16.9.2125.
Riso P, Martini D, Møller P, Loft S, Bonacina G, Moro M, et al. DNA damage and repair activity after broccoli intake in young healthy smokers. Mutagenesis. 2010;25(6):595–602. doi: 10.1093/mutage/geq045.
Charron CS, Clevidence BA, Albaugh GA, Kramer MH, Vinyard BT, Milner JA, et al. Assessment of DNA damage and repair in adults consuming allyl isothiocyanate or Brassica vegetables. J Nutr Biochem. 2013;24(5):894–902. doi: 10.1016/j.jnutbio.2012.06.004.
Coode-Bate J, Sivapalan T, Melchini A, Saha S, Needs PW, Dainty JR, et al. Accumulation of Dietary S‐Methyl Cysteine Sulfoxide in Human Prostate Tissue. Mol Nutr Food Res. 2019;63(20). doi: 10.1002/mnfr.201900461.
Gee JR, Saltzstein DR, Messing E, Kim KM, Kolesar J,Huang W, et al. Phase Ib placebo-controlled, tissue biomarker trial of diindolylmethane (BR-DIMNG) in patients with prostate cancer who are undergoing prostatectomy. Eur J Cancer Prev. 2016;25(4):312–20. doi: 10.1097/CEJ.0000000000000189.
Atwell LL, Zhang Z, Mori M, Farris PE, Vetto JT, Naik AM, et al. Sulforaphane Bioavailability and Chemopreventive Activity in Women Scheduled for Breast Biopsy. Cancer Prev Res (Phila). 2015;8(12):1184–91. doi: 10.1158/1940-6207.CAPR-15-0119.
Laidlaw M, Cockerline CA, Sepkovic DW. Effects of A Breast-Health Herbal Formula Supplement on Estrogen Metabolism in Pre- and Post-Menopausal Women not Taking Hormonal Contraceptives or Supplements: A Randomized Controlled Trial. Breast Cancer (Auckl). 2010;4(1):85. doi: 10.4137/BCBCR.S6505.
Burow M, Atwell S, Francisco M, Kerwin RE, Halkier BA, Kliebenstein DJ. The glucosinolate biosynthetic gene AOP2 mediates feed-back regulation of jasmonic acid signaling in Arabidopsis. Mol Plant. 2015;8(8):1201–12012. doi:10.1016/j.molp.2015.03.001.
Sønderby IE, Geu-flores F, Halkier BA. Biosynthesis of glucosinolates – gene discovery and beyond. Trends Plant Sci. 2010;15(5):283–90. doi: 10.1016/j.tplants.2010.02.005.
Pino Del Carpio D, Basnet RK, Arends D, Lin K, De Vos RCH, Muth D, et al. Regulatory Network of Secondary Metabolism in Brassica rapa: Insight into the Glucosinolate Pathway. PLoS One. 2014;9(9):e107123. doi: 10.1371/journal.pone.0107123.
Zhang Y, Talalay P, Cho CG, Posner GH. A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proceedings of the National Academy of Sciences. 1992;89:2399–403. doi: 10.1073/pnas.89.6.2399.
Conaway CC, Wang CX, Pittman B, Yang YM, Schwartz JE, Tian D, et al. Phenethyl isothiocyanate and sulforaphane and their N-acetylcysteine conjugates inhibit malignant progression of lung adenomas induced by tobacco carcinogens in A/J mice. Cancer Res. 2005;65(18):8548–57. doi: 10.1158/0008-5472.CAN-05-0237.
Chung FL, Conaway CC, Rao C V., Reddy BS. Chemoprevention of colonic aberrant crypt foci in Fischer rats by sulforaphane and phenethyl isothiocyanate. Carcinogenesis. 2000;21(12):2287–91. doi:10.1093/carcin/21.12.2287.
Zhang Y, Kensler TW, Cho CG, Posner GH, Talalay P. Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates. Proceedings of the National Academy of Sciences. 1994;91:3147–50. doi: 10.1073/pnas.91.8.3147.
Singh A V., Xiao D, Lew KL, Dhir R, Singh S V.Sulforaphane induces caspase-mediated apoptosis in cultured PC-3 human prostate cancer cells and retards growth of PC-3 xenografts in vivo. Carcinogenesis. 2004;25(1):83–90. doi: 10.1093/carcin/bgg178.
Kallifatidis G, Rausch V, Baumann B, Apel A, Beckermann BM, Groth A, et al. Sulforaphane targets pancreatic tumour-initiating cells by NF- B-induced antiapoptotic signalling. Gut. 2009;58(7):949–63. doi: 10.1136/gut.2008.149039.
Bradlow HL. Indole-3-carbinol as a chemoprotective agent in breast and prostate cancer. In Vivo. 2008;22(4):441–5. doi: 10.1093/jn/134.12.3493S.
Aronchik I, Bjeldanes LF, Firestone GL. Direct inhibition of elastase activity by indole-3-carbinol triggers a CD40-TRAF regulatory cascade that disrupts NF-κB transcriptional activity in human breast cancer cells. Cancer Res. 2010;70(12):4961–71. doi: 10.1158/0008-5472.CAN-09-3349.
Jeong YM, Li H, Kim SY, Yun HY, Baek KJ, Kwon NS, et al. Indole-3-carbinol inhibits prostate cancer cell migration via degradation of β-catenin. Oncol Res. 2011;19(5):237–43. doi: 10.3727/096504011x12970940207922.
Megna BW, Carney PR, Nukaya M, Geiger P, Kennedy GD. Indole-3-carbinol induces tumor cell death: function follows form. Journal of Surgical Research. 2016;204(1):47–54. doi: 10.1016/j.jss.2016.04.021.
Lee CM, Lee J, Nam MJ, Park SH. Indole-3-Carbinol Induces Apoptosis in Human Osteosarcoma MG-63 and U2OS Cells. Biomed Res Int. 2018;1–13. doi: 10.1155/2018/7970618.
Warin R, Chambers WH, Potter DM, Singh S V. Prevention of mammary carcinogenesis in MMTV-neu mice by cruciferous vegetable constituent benzyl isothiocyanate. Cancer Res. 2009;69(24):9473–80. doi: 10.1158/0008-5472.CAN-09-2960.
Warin R, Xiao D, Arlotti JA, Bommareddy A, Singh S V. Inhibition of human breast cancer xenograft growth by cruciferous vegetable constituent benzyl isothiocyanate. Mol Carcinog. 2010;49(5):500–7. doi: 10.1002/mc.20600.
Rao C V. Benzyl isothiocyanate: Double trouble for breast cancer cells. Cancer Prevention Research. 2013;6(8):760–3. doi: 10.1158/1940-6207.CAPR-13-0242.
Lai KC, Huang AC, Hsu SC, Kuo CL, Yang JS, Wu SH, et al. Benzyl Isothiocyanate (BITC) Inhibits Migration and Invasion of Human Colon Cancer HT29 Cells by Inhibiting Matrix Metalloproteinase-2/-9 and Urokinase Plasminogen (uPA) through PKC and MAPK Signaling Pathway. J Agric Food Chem. 2010;58(5):2935–42. doi: 10.1021/jf9036694.
Boreddy SR, Pramanik KC, Srivastava SK. Pancreatic tumor suppression by benzyl isothiocyanate is associated with inhibition of PI3K/AKT/FOXO pathway. Clinical Cancer Research.2011;17(7):1784–95. doi: 10.1158/1078-0432.CCR-10-1891.
Nowicki D, Rodzik O, Herman-Antosiewicz A, Szalewska-Pałasz A. Isothiocyanates as effective agents against enterohemorrhagic Escherichia coli: insight to the mode of action. Sci Rep. 2016;6:1–12. doi: 10.1038/srep22263.
Gasper A V., Traka M, Bacon JR, Smith JA, Taylor MA, Hawkey CJ, et al. Consuming Broccoli Does Not Induce Genes Associated with Xenobiotic Metabolism and Cell Cycle Control in Human Gastric Mucosa. J Nutr;137(7):1718–24. doi: 10.1093/jn/137.7.1718.
Zhang Z, Garzotto M, Davis EW, Mori M, Stoller WA, Farris PE, et al. Sulforaphane Bioavailability and Chemopreventive Activity in Men Presenting for Biopsy of the Prostate Gland: A Randomized Controlled Trial. Nutr Cancer. 2020;72(1):74–87. doi: 10.1080/01635581.2019.1619783.
Kensler TW, Chen JG, Egner PA, Fahey JW, Jacobson LP, Stephenson KK, et al. Effects of glucosinolate-rich broccoli sprouts on urinary levels of aflatoxin-DNA adducts and phenanthrene tetraols in a randomized clinical trial in He Zuo township, Qidong, People’s Republic of China. Cancer Epidemiology, Biomarkers & Prevention. 2005;14(11 Pt 1):2605–13. doi: 10.1158/1055-9965.EPI-05-0368.
Egner PA, Chen JG, Zarth AT, Ng DK, Wang JB, Kensler KH, et al. Rapid and sustainable detoxication of airborne pollutants by broccoli sprout beverage: results of a randomized clinical trial in China. Cancer Prev Res (Phila). 2014;7(8):813–23. doi: 10.1158/1940-6207.CAPR-14-0103.
Charron CS, Novotny JA, Jeffery EH, Kramer M, Ross SA, Seifried HE. Consumption of baby kale increased cytochrome P450 1A2 (CYP1A2) activity and influenced bilirubin metabolism in a randomized clinical trial. J Funct Foods. 2020;64:103624. doi: /10.1016/j.jff.2019.103624.
Naik R, Nixon S, Lopes A, Godfrey K, Hatem MH, Monaghan JM. A randomized phase II trial of indole-3-carbinol in the treatment of vulvar intraepithelial neoplasia. Int J Gynecol Cancer. 2006;16(2):786–90. doi: 10.1111/j.1525-1438.2006.00386.x.
Castãon A, Tristram A, Mesher D, Powell N, Beer H, Ashman S, et al. Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial. Br J Cancer. 2012;106(1):45–52. doi: 10.1038/bjc.2011.496.
Boldry EJ, Yuan JM, Carmella SG, Wang R, Tessier K, Hatsukami DK, et al. Effects of 2-Phenethyl Isothiocyanate on Metabolism of 1,3-Butadiene in Smokers. Cancer Prev Res (Phila). 2020;13(1):91–100. doi: 10.1158/1940-6207.CAPR-19-0296.
Yuan JM, Murphy SE, Stepanov I, Wang R, Carmella SG, Nelson HH, et al. 2-Phenethyl Isothiocyanate, Glutathione S-transferase M1 and T1 Polymorphisms, and Detoxification of Volatile Organic Carcinogens and Toxicants in Tobacco Smoke. Cancer Prev Res (Phila). 2016;9(7):598–606. doi: 10.1158/1940-6207.CAPR-16-0032.
Yuan JM, Stepanov I, Murphy SE, Wang R, Allen S, Jensen J, et al. Clinical Trial of 2-Phenethyl Isothiocyanate as an Inhibitor of Metabolic Activation of a Tobacco-Specific Lung Carcinogen in Cigarette Smokers. Cancer Prev Res (Phila). 2016;9(5):396–405. doi: 10.1158/1940-6207.CAPR-15-0380.