LIU Xinxin, ZOU Ping, ZHU Chenchen, et al. Research Progress on Anticancer Effects of Sulforaphane[J]. Science and Technology of Food Industry, 2024, 45(12): 386−394. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2023080072.
Citation: LIU Xinxin, ZOU Ping, ZHU Chenchen, et al. Research Progress on Anticancer Effects of Sulforaphane[J]. Science and Technology of Food Industry, 2024, 45(12): 386−394. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2023080072.

Research Progress on Anticancer Effects of Sulforaphane

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  • Received Date: March 14, 2023
  • Available Online: April 20, 2024
  • Cancer is the leading cause of mortality in human health, with the highest mortality rate among all diseases. Unfortunately, most of the current cancer treatments inevitably come with certain side effects. Therefore, a significant amount of research is focused on the development of safe and effective anticancer drugs. Sulforaphane is one of the most bioactive natural compounds isolated from cruciferous plants. Numerous studies show its anti-cancer, antioxidant, and antiviral properties, as well as its anticancer mechanisms. Sulforaphane can inhibit the growth of cancer cells by regulating the cell cycle, inhibiting cell migration and invasion, and inhibiting the expression of apoptosis related proteins. It can also inhibit the occurrence and development of cancer cells through anti-inflammatory and antioxidant measures. Some reports also indicate that sulforaphane can impede the development of cancer cells through its anti-inflammatory and antioxidant effects. Compared to most traditional cancer treatment methods, sulforaphane is much safer and more reliable. It is also more readily available and has great anticancer potential. This paper review the anticancer mechanisms of sulforaphane over the past two years and provide the corresponding theoretical basis for further research on the anticancer effects of sulforaphane.
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  • [1]
    SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020:globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA-A: A Cancer Journal for Clinicians,2021,71(3):209−249.
    [2]
    XIA C F, DONG X S, LI H, et al. Cancer statistics in China and United States, 2022:profiles, trends, and determinants[J]. Chinese Medical Journal,2022,135(5):584−590.
    [3]
    ZHANG Y, TAN L X, LI C, et al. Sulforaphane alter the microbiota and mitigate colitis severity on mice ulcerative colitis induced by dss[J]. AMB Express,2020,10(1):119−127.
    [4]
    IAHTISHAM-UL-HAQ, KHAN S, AWAN K A, et al. Sulforaphane as a potential remedy against cancer:Comprehensive mechanistic review[J]. Journal of Food Biochemistry,2021,46(3):e13886.
    [5]
    AUNE D, GIOVANNUCCI E, BOFFETTA P, et al. Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality-a systematic review and dose-response meta-analysis of prospective studies[J]. International Journal of Epidemiology,2017,46(3):1029−1056.
    [6]
    CHENG L, WAN K, LIANG H, et al. Sulforaphane and sulforaphane[A]. Glucosinolates:Properties, Recovery, and Applications, 2020, 281−232.
    [7]
    SINHA S, SHARMA S, SHARMA A, et al. Sulforaphane-cisplatin combination inhibits the stemness and metastatic potential of tnbcs via down regulation of sirtuins-mediated emt signaling axis[J]. Phytomedicine,2021,84:153492.
    [8]
    VANDUCHOVA A, ANZENBACHER P, ANZENBACHEROVA E. Isothiocyanate from broccoli, sulforaphane, and its properties[J]. Journal of Medicinal Food,2018,22(2):121−126.
    [9]
    DINKOVA-KOSTOVA A T, FAHEY J W, KOSTOV R V, et al. KEAP1 and Done? targeting the NRF2 pathway with sulforaphane[J]. Trends in Food Science & Technology, 2017, 69(Pt B):257−269.
    [10]
    JAMES D, DEVARAJ S, BELLUR P, et al. Novel concepts of broccoli sulforaphanes and disease:induction of phase II antioxidant and detoxification enzymes by enhanced-glucoraphanin broccoli[J]. Nutrition Reviews,2012,70(11):654−665.
    [11]
    MAHN A, CASTILLO A. Potential of sulforaphane as a natural immune system enhancer:A review[J]. Molecules,2021,26(3):752−783.
    [12]
    SE-RAN J, CHEEMA A, BOSE C, et al. Multi-omic analysis reveals the anti-aging impact of sulforaphane on the microbiome and metabolome[J]. ResearchGate, 2020.
    [13]
    LI Z S, LIU Y M, FANG Z Y, et al. Natural sulforaphane from broccoli seeds against influenza a virus replication in mdck cells[J]. Natural Product Communications, 2019, 14(6):1934578X1985822.
    [14]
    AXELSSON A S, TUBBS E, MECHAM B, et al. Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes[J]. Science Translational Medicine,2017,9(394):eaah4477.
    [15]
    JAYAKUMAR T, CHEN W F, LU W J, et al. A novel antithrombotic effect of sulforaphane via activation of platelet adenylate cyclase:ex vivo and in vivo studies[J]. The Journal of Nutritional Biochemistry,2013,24(6):1086−1095.
    [16]
    JAKUBIKOVA J, CERVI D, OOI M, et al. Anti-tumor activity and signaling events triggered by the isothiocyanates, sulforaphane and phenethyl isothiocyanate, in multiple myeloma[J]. Haematologica,2011,96(8):1170−1179.
    [17]
    MILCZAREK M, POGORZELSKA A, WIKTORSKA K. Synergistic interaction between 5-fu and an analog of sulforaphane-2-oxohexyl isothiocyanate-in an in vitro colon cancer model[J]. Molecules,2021,26(10):3019−3032. doi: 10.3390/molecules26103019
    [18]
    WANG Y, WU H Z, DONG N N, et al. Sulforaphane induces s-phase arrest and apoptosis via p53-dependent manner in gastric cancer cells[J]. Scientific Reports,2021,11(1):2504. doi: 10.1038/s41598-021-81815-2
    [19]
    YI H X, LI Z M, LIU X X, et al. Therapeutic mechanism of lapatinib combined with sulforaphane on gastric cancer[J]. Evidence-Based Complementary and Alternative Medicine,2021,eCAM:9933274.
    [20]
    KAN S F, WANG J, SUN G X. Sulforaphane regulates apoptosis-and proliferation related signaling pathways and synergizes with cisplatin to suppress human ovarian cancer[J]. International Journal of Molecular Medicine,2018,42(5):2447−2458.
    [21]
    JAMASBI E, HAMELIAN M, HOSSAIN M A, et al. The cell cycle, cancer development and therapy[J]. Mol Biol Rep. 2022, 49(11):10875−10883.
    [22]
    BLOOM J, CROSS F R. Multiple levels of cyclin specificity in cell-cycle control[J]. Molecular Cell Biology,2007,8(2):149−160.
    [23]
    MATTHEWS H K, BERTOLI C, DE BRUIN RAM. Cell cycle control in cancer[J]. Nature Reviews Molecular Cell Biology,2021,23(1):74−88.
    [24]
    LAPENNA S, GIORDANO A. Cell cycle kinases as therapeutic targets for cancer[J]. Nature Reviews Drug Discovery,2009,8(7):547−566.
    [25]
    HUANG B, LEI S X, WANG D, et al. Sulforaphane exerts anticancer effects on human liver cancer cells via induction of apoptosis and inhibition of migration and invasion by targeting MAPK7 signalling pathway[J]. Journal of BUON,2020,25(2):959−964.
    [26]
    MENG W, MENG J, ZHANG F, et al. Sulforaphane overcomes t790m-mediated gefitinib resistance in vitro through epithelial-mesenchymal transition[J]. Journal of Physiology and Pharmacology,2021,72(5):741−749.
    [27]
    WANG L P, TIAN Z F, YANG Q, et al. Sulforaphane inhibits thyroid cancer cell growth and invasiveness through the reactive oxygen species-dependent pathway[J]. Oncotarget,2015,6(28):25917−25931. doi: 10.18632/oncotarget.4542
    [28]
    TOMASELLO B, DOMENICA M, DI M, et al. Rapha myr, a blend of sulforaphane and myrosinase, exerts antitumor and anoikis- sensitizing effects on human astrocytoma cells modulating sirtuins and dna methylation[J]. International Journal of Molecular Sciences,2020,21(15):5328−5353. doi: 10.3390/ijms21155328
    [29]
    王凡平, 乔彩娟, 孙彦威, 等. 莱菔硫烷诱导急性髓系白血病KG1a和KG1细胞G2/M期阻滞的作用和相关机制[J]. 中国实验血液学杂志,2021,29(4):1050−1055. [WANG F P, QIAO C J, SUN Y W, et al. Effect and mechanism of sulforaphane on G2/ M phase arrest of acute Myeloid Leukemia KG1a and KG1 Cells[J]. Journal of Experimental Hematology,2021,29(4):1050−1055.]

    WANG F P, QIAO C J, SUN Y W, et al. Effect and mechanism of sulforaphane on G2/ M phase arrest of acute Myeloid Leukemia KG1a and KG1 Cells[J]. Journal of Experimental Hematology, 2021, 29(4): 1050−1055.
    [30]
    SUSKI J M, BRAUN M, STRMISKA V, et al. Targeting cell-cycle machinery in cancer[J]. Cancer Cell,2021,39(6):759−778. doi: 10.1016/j.ccell.2021.03.010
    [31]
    ROYSTON K J, PAUL B, NOZELL S, et al. Withaferin a and sulforaphane regulate breast cancer cell cycle progression through epigenetic mechanisms[J]. Experimental Cell Research,2018,368(1):67−74. doi: 10.1016/j.yexcr.2018.04.015
    [32]
    DAVIS F M, STEWART T A, THOMPSON E W, et al. Targeting emt in cancer:opportunities for pharmacological intervention[J]. Trends in Pharmacological Sciences,2014,35(9):479−488. doi: 10.1016/j.tips.2014.06.006
    [33]
    LI C L, YAN Z, PENG X H, et al. Sulforaphane inhibits invasion via activating erk1/2 signaling in human glioblastoma u87mg and u373mg cells[J]. PLoS One,2014,9(2):e90520. doi: 10.1371/journal.pone.0090520
    [34]
    LIN J S, XU Y L, ZHAO X, et al. Anticancer activity of sulforaphane against human hepatoblastoma cells involves apoptosis, autophagy and inhibition ofβ-catenin signaling pathway[J]. Archives of Medical Science,2020(1):1−9.
    [35]
    谢金芳, 曹春雨, 任雪, 等. SFN对小鼠乳腺癌4T1细胞上皮-间质转化, 增殖和迁移的影响研究[J]. 中国癌症杂志,2021,31(7):605−615. [XIE J F, CAO C Y, REN X, et al. Effects of sulforaphane on epithelial-mesenchymal transition, proliferation and migration of mouse breast cancer 4T1 cells[J]. China Oncology,2021,31(7):605−615.]

    XIE J F, CAO C Y, REN X, et al. Effects of sulforaphane on epithelial-mesenchymal transition, proliferation and migration of mouse breast cancer 4T1 cells[J]. China Oncology, 2021, 31(7): 605−615.
    [36]
    HAN S C, WANG Z, LIU J N, et al. Mir-29a-3p-dependent col3a1 and col5a1 expression reduction assists sulforaphane to inhibit gastric cancer progression[J]. Biochemical Pharmacology,2021,188:114539. doi: 10.1016/j.bcp.2021.114539
    [37]
    ALHAZMI N, PAI C P, ALBAQAMI A, et al. The promyelocytic leukemia protein isoform pml1 is an oncoprotein and a direct target of the antioxidant sulforaphane (sfn)[J]. Biochimica ET Biophysica Acta-Molecular Cell Research,2020,1867(8):118707. doi: 10.1016/j.bbamcr.2020.118707
    [38]
    EZEKA G, ADHIKARY G, KANDASAMY S, et al. Sulforaphane inhibits prmt5 and mep50 function to suppress the mesothelioma cancer cell phenotype[J]. Molecular Carcinogenesis,2021,60(7):429−439. doi: 10.1002/mc.23301
    [39]
    SIMÕES B M, SANTIAGO-GÓMEZ A, CHIODO C, et al. Targeting stat3 signaling using stabilised sulforaphane (sfx-01) inhibits endocrine resistant stem-like cells in er-positive breast cancer[J]. Oncogene,2020,39(25):4896−4908. doi: 10.1038/s41388-020-1335-z
    [40]
    VERMEULEN K, BOCKSTAELE D R, BERNEMAN Z N. Apoptosis:mechanisms and relevance in cancer[J]. Annals of Hematology,2005,84(10):627−639. doi: 10.1007/s00277-005-1065-x
    [41]
    PENG F, LIAO M R, et al. Regulated cell death (rcd) in cancer:key pathways and targeted therapies[J]. Signal Transduction and Targeted Therapy,2022,7(1):286−352. doi: 10.1038/s41392-022-01110-y
    [42]
    GROSS A, MCDONNELL J M, KORSMEYER S J. Bcl-2 family members and the mitochondria in apoptosis[J]. Genes & Development,1999,13(15):1899−1911.
    [43]
    LU Z M, REN Y D, YANG L, et al. Inhibiting autophagy enhances sulforaphane-induced apoptosis via targeting Nrf2 in esophageal squamous cell carcinoma[J]. Acta Pharmaceutica Sinica,2020,11(5):1246−1260.
    [44]
    顾文燕, 李丽, 吴敏. SFN通过调节Bax表达降低结肠癌细胞株5-氟尿嘧啶的耐药[J]. 中国现代中药,2019,21(4):458−463. [GU W Y, LI L, WU M. Effect of sulforaphane on decrease of drug resistance of colon cancer cells to 5-fu via regulating bax expression[J]. Modern Chinese Medicine,2019,21(4):458−463.]

    GU W Y, LI L, WU M. Effect of sulforaphane on decrease of drug resistance of colon cancer cells to 5-fu via regulating bax expression[J]. Modern Chinese Medicine, 2019, 21(4): 458−463.
    [45]
    MOSS S F, BLASER M J. Mechanisms of disease:Inflammation and the origins of cancer[J]. Nature Clinical Practice Oncology,2005,2(2):90−97,113. doi: 10.1038/ncponc0081
    [46]
    CANDIDO J, HAGEMANN T. Cancer-related inflammation[J]. Journal of Clinical Immunology,2013,33(1):79−84.
    [47]
    SIM H, LEE W, CHOO S, et al. Sulforaphane alleviates particulate matter-induced oxidative stress in human retinal pigment epithelial cells[J]. Frontiers in Medicine,2021,8:685032. doi: 10.3389/fmed.2021.685032
    [48]
    BRYAN N B, DORFLEUTNER A, ROJANASAKUL Y, et al. Activation of inflammasomes requires intracellular redistribution of the apoptotic speck-like protein containing a caspase recruitment domain[J]. Journal of Immunology,2009,182(5):3173−3182. doi: 10.4049/jimmunol.0802367
    [49]
    GALDIERO M R, MARONE G, MANTOVANI A. Cancer inflammation and cytokines[J]. Cold Spring Harbor Perspectives in Biology,2018,10(8):a028662. doi: 10.1101/cshperspect.a028662
    [50]
    PROPPER D J, BALKWILL F R. Harnessing cytokines and chemokines for cancer therapy[J]. Nature Reviews Clinical Oncology,2022,19(4):237−253. doi: 10.1038/s41571-021-00588-9
    [51]
    ZHU W, YU J B, NIE Y, et al. Disequilibrium of M1 and M2 macrophages correlates with the development of experimental inflammatory bowel diseases[J]. Immunological Investigations,2014,43(7):638−652. doi: 10.3109/08820139.2014.909456
    [52]
    SUN Y Y, TANG J Q, LI C, et al. Sulforaphane attenuates dextran sodium sulphate induced intestinal inflammation via IL-10/stat3 signaling mediated macrophage phenotype switching[J]. Food Science and Human Wellness,2022,11(1):129−142. doi: 10.1016/j.fshw.2021.07.014
    [53]
    LOZANO-ONDOUA A N, SYMONS-LIGUORI A M, VANDERAH T W. Cancer-induced bone pain:mechanisms and models[J]. Neuroscience Letters, 2013, 557(pt A):52−59.
    [54]
    FU J, XU M, XU L S, et al. Sulforaphane alleviates hyperalgesia and enhances analgesic potency of morphine in rats with cancer-induced bone pain[J]. European Journal of Pharmacology,2021,909:174412. doi: 10.1016/j.ejphar.2021.174412
    [55]
    WHITE J P. IL-6, cancer and cachexia:Metabolic dysfunction creates the perfect storm[J]. Translation Cancer Research,2017,6(S2):S280−S285. doi: 10.21037/tcr.2017.03.52
    [56]
    AL-BAKHEIT A, ABU-QATOUSEH L. Sulforaphane from broccoli attenuates inflammatory hepcidin by reducing IL-6 secretion in human HepG2 cells[J]. Journal of Functional Foods,2020,75(2020):1−7.
    [57]
    FREUND A, CHAUVEAU C, BROUILLET J P, et al. IL-8 expression and its possible relationship with estrogen-receptor-negative status of breast cancer cells[J]. Oncogene,2003,22(2):256−265. doi: 10.1038/sj.onc.1206113
    [58]
    BUCK I, MORCEAU F, GRIGORAKAKI C, et al. Linking anemia to inflammation and cancer:The crucial role of TNF-α[J]. Biochemical Pharmacology,2008,77(10):1572−1579.
    [59]
    杨艳华, 梁丽琴. SFN对胃癌细胞生物学特征的影响及其机制研究[J]. 中国药师,2019,22(5):840−845. [YANG Y H, LIANG L Q. Effect of sulforaphane on biological activity of gastric cancer cells and underlying mechanisms[J]. Chinese Pharmacist,2019,22(5):840−845.]

    YANG Y H, LIANG L Q. Effect of sulforaphane on biological activity of gastric cancer cells and underlying mechanisms[J]. Chinese Pharmacist, 2019, 22(5): 840−845.
    [60]
    SPORN M B, LIBY K T. Nrf2 and cancer:the good, the bad and the importance of context[J]. Nature Reviews Cancer,2012,12(8):564−571. doi: 10.1038/nrc3278
    [61]
    CHEN W M, JIANG T, WANG H H, et al. Does Nrf2 contribute to p53-mediated control of cell survival and death?[J]. Antioxidants & Redox Signaling,2012,17(12):1670−1675.
    [62]
    GWON Y, OH J, KIM J S. Sulforaphane induces colorectal cancer cell proliferation through nrf2 activation in a p53-dependent manner[J]. Applied Biological Chemistry,2020,63(1):86−96. doi: 10.1186/s13765-020-00578-y
    [63]
    RONG Y, YUAN C H, QU Z, et al. Doxorubicin resistant cancer cells activate myeloid-derived suppressor cells by releasing pge2[J]. Scientific Reports,2016,6(1):23824. doi: 10.1038/srep23824
    [64]
    RONG Y, HUANG L X, YI K Z, et al. Co-administration of sulforaphane and doxorubicin attenuates breast cancer growth by preventing the accumulation of myeloid-derived suppressor cells-sciencedirect[J]. Cancer Letter,2020,493:189−196. doi: 10.1016/j.canlet.2020.08.041
    [65]
    AHMED S M, LUO L, NAMANI A, et al. Nrf2 signaling pathway:pivotal roles in inflammation[J]. Biochimica et Biophysica Acta-Molecular Basis of Disease,2017,1863(2):585−597. doi: 10.1016/j.bbadis.2016.11.005
    [66]
    MPAB C, ECLB C, IA B, et al. Dietary supplementation with sulforaphane ameliorates skin aging through activation of the Keap1-Nrf2 pathway[J]. The Journal of Nutritional Biochemistry,2021,98:108817. doi: 10.1016/j.jnutbio.2021.108817
    [67]
    SANTOS P, MACHADO A, GRANDIS R D, et al. Effects of sulforaphane on the oxidative response, apoptosis, and the transcriptional profile of human stomach mucosa cells in vitro[J]. Genetic Toxicology and Environmental Mutagenesis,2020,854:503201.
    [68]
    LIN S B, GREGORY R I. MicroRNA biogenesis pathways in cancer[J]. Nature reviews Cancer,2015,15(6):321−333. doi: 10.1038/nrc3932
    [69]
    RUPAIMOOLE R, SLACK F J. MicroRNA therapeutics:towards a new era for the management of cancer and other diseases[J]. Nature Reviews Drug Discovery,2017,16(3):203−222. doi: 10.1038/nrd.2016.246
    [70]
    PENG Z T, GU P. Sulforaphane suppresses autophagy during the malignant progression of gastric carcinoma via activating miR-4521/PIK3R3 pathway[J]. Human & Experimental Toxicology,2021,40(12):S711−S720.
    [71]
    GEORGIKOU C, BUGLIONI L, BREMERICH M, et al. Novel broccoli sulforaphane-based analogues inhibit the progression of pancreatic cancer without side effects[J]. Biomolecules,2020,10(5):769−785. doi: 10.3390/biom10050769
    [72]
    CHENG T, CHEN J, HUANG X F, et al. CT1-3, a novel magnolol-sulforaphane hybrid suppresses tumorigenesis through inducing mitochondria-mediated apoptosis and inhibiting epithelial mesenchymal transition[J]. European Journal of Medicinal Chemistry,2020,199:112441. doi: 10.1016/j.ejmech.2020.112441
    [73]
    GASPARELLO J, GAMBARI L, PAPI C, et al. High levels of apoptosis are induced in the human colon cancer ht-29 cell line by co-administration of sulforaphane and a peptide nucleic acid targeting mir-15b-5p[J]. Nucleic Acid Therapeutics,2020,30(3):164−174. doi: 10.1089/nat.2019.0825
    [74]
    SANTANA-GÁLVEZ J, VILLELA-CASTREJÓN J, SERNA-SALDÍVAR S O, et al. Synergistic combinations of curcumin, sulforaphane, and dihydrocaffeic acid against human colon cancer cells[J]. International Journal of Molecular Sciences,2020,21(9):3108−3128. doi: 10.3390/ijms21093108
    [75]
    XU Y, HAN X Y, LI Y Y, et al. Sulforaphane mediates glutathione depletion via polymeric nanoparticles to restore cisplatin chemosensitivity[J]. ACS nano,2019,13(11):13445−13455. doi: 10.1021/acsnano.9b07032
    [76]
    GRECO G, SCHNEKENBURGER M, CATANZARO E, et al. Discovery of Sulforaphane as an inducer of ferroptosis in U-937 leukemia cells:expanding its anticancer potential[J]. Cancers (Basel),2021,14(1):76−92. doi: 10.3390/cancers14010076
    [77]
    AKIYOSHI S, KIKUCHI H, KURIBAYASHI F, et al. Sulforaphane displays the growth inhibition, cytotoxicity and enhancement of retinoic acid-induced superoxide-generating activity in human monoblastic U937 cells[J]. Fundamental Toxicological Sciences,2019,6(8):319−325. doi: 10.2131/fts.6.319
    [78]
    RORKE E A, ADHIKARY G, SZMACINSKI H, et al. Sulforaphane covalently interacts with the transglutaminase 2 cancer maintenance protein to alter its structure and suppress its activity[J]. Molecular Carcinogenesis,2021,61(1):19−32.
    [79]
    XIA Y, KANG T W, JUNG D Y, et al. Sulforaphane inhibits nonmuscle invasive bladder cancer cells proliferation through suppression of hif-1α-mediated glycolysis in hypoxia[J]. Journal of Agricultural and Food Chemistry,2019,67(28):7844−7854. doi: 10.1021/acs.jafc.9b03027
    [80]
    AMER M A, MOHAMED T R, RAHMAN R A A, et al. Studies on exogenous elicitors promotion of sulforaphane content in broccoli sprouts and its effect on the MDA-MB-231 breast cancer cell line[J]. Annals of Agricultural Sciences,2021,66(1):46−52. doi: 10.1016/j.aoas.2021.02.001
    [81]
    GU H F, REN F Z, MAO X Y, et al. Mineralized and GSH-responsive hyaluronic acid based nano-carriers for potentiating repressive effects of sulforaphane on breast cancer stem cells-like properties[J]. Carbohydrate Polymers,2021,269:118294−118305. doi: 10.1016/j.carbpol.2021.118294
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