Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Systematic Review Article

Protective Effect of Isothiocyanates from Cruciferous Vegetables on Breast Cancer: Epidemiological and Preclinical Perspectives

Author(s): Suong N.T. Ngo* and Desmond B. Williams

Volume 21, Issue 11, 2021

Published on: 24 September, 2020

Page: [1413 - 1430] Pages: 18

DOI: 10.2174/1871520620666200924104550

Price: $65

Abstract

Background: The effect of cruciferous vegetable intake on breast cancer survival is controversial at present. Glucosinolates are the naturally occurring constituents found across the cruciferous vegetables. Isothiocyanates are produced from the hydrolysis of glucosinolates and this reaction is catalysed by the plant-derived enzyme myrosinase. The main Isothiocyanates (ITCs) from cruciferous vegetables are sulforaphane, benzyl ITC, and phenethyl ITC, which had been intensively investigated over the last decade for their anti-breast cancer effects.

Objective: The aim of this article is to systematically review the evidence from all types of studies, which examined the protective effect of cruciferous vegetables and/or their isothiocyanate constituents on breast cancer.

Methods: A systematic review was conducted in Pubmed, EMBASE, and the Cochrane Library from inception to 27 April 2020. Peer-reviewed studies of all types (in vitro studies, animal studies, and human studies) were selected.

Results: The systematic literature search identified 16 human studies, 4 animal studies, and 65 in vitro studies. The effect of cruciferous vegetables and/or their ITCs intake on breast cancer survival was found to be controversial and varied greatly across human studies. Most of these trials were observational studies conducted in specific regions, mainly in the US and China. Substantial evidence from in vitro and animal studies was obtained, which strongly supported the protective effect of sulforaphane and other ITCs against breast cancer. Evidence from in vitro studies showed that sulforaphane and other ITCs reduced cancer cell viability and proliferation via multiple mechanisms and pathways. Isothiocyanates inhibited cell cycle, angiogenesis and epithelial mesenchymal transition, as well as induced apoptosis and altered the expression of phase II carcinogen detoxifying enzymes. These are the essential pathways that promote the growth and metastasis of breast cancer. Noticeably, benzyl ITC showed a significant inhibitory effect on breast cancer stem cells, a new dimension of chemo-resistance in breast cancer treatment. Sulforaphane and other ITCs displayed anti-breast cancer effects at variable range of concentrations and benzyl isothiocyanate appeared to have a relatively lower inhibitory concentration IC50. The mechanisms underlying the cancer protective effect of sulforaphane and other ITCs have also been highlighted in this article.

Conclusion: Current preclinical evidence strongly supports the role of sulforaphane and other ITCs as potential therapeutic agents for breast cancer, either as adjunct therapy or combined therapy with current anti-breast cancer drugs, with sulforaphane displaying the greatest potential.

Keywords: Anti-breast cancer, benzyl isothiocyanate, cruciferous vegetables, human breast cancer, phenethyl isothiocyanate, protective action, sulforaphane.

« Previous Next »
Graphical Abstract

[1]
Verhoeven, D.T.; Goldbohm, R.A.; van Poppel, G.; Verhagen, H.; van den Brandt, P.A. Epidemiological studies on brassica vegetables and cancer risk. Cancer Epidemiol. Biomarkers Prev., 1996, 5(9), 733-748.
[PMID: 8877066]
[2]
Fahey, J.W.; Zalcmann, A.T.; Talalay, P. The chemical diversity and distribution of glucosinolates and isothiocyanates among plants. Phytochemistry, 2001, 56(1), 5-51.
[http://dx.doi.org/10.1016/S0031-9422(00)00316-2] [PMID: 11198818]
[3]
Tijhuis, M.J.; Wark, P.A.; Aarts, J.M.; Visker, M.H.; Nagengast, F.M.; Kok, F.J.; Kampman, E. GSTP1 and GSTA1 polymorphisms interact with cruciferous vegetable intake in colorectal adenoma risk. Cancer Epidemiol. Biomarkers Prev., 2005, 14(12), 2943-2951.
[http://dx.doi.org/10.1158/1055-9965.EPI-05-0591] [PMID: 16365014]
[4]
Sofrata, A.; Brito, F.; Al-Otaibi, M.; Gustafsson, A. Short term clinical effect of active and inactive Salvadora persica miswak on dental plaque and gingivitis. J. Ethnopharmacol., 2011, 137(3), 1130-1134.
[http://dx.doi.org/10.1016/j.jep.2011.07.034] [PMID: 21798329]
[5]
Hecht, S.S. Chemoprevention by Isothiocyanates.In: Promising cancer chemopreventive agents; Kelloff, G.J.; Hawk, E.T.; Sigman, C.C., Eds.; Humana Press: Totowa, NJ, 2004, pp. 21-35.
[http://dx.doi.org/10.1007/978-1-59259-767-3_2]
[6]
Shapiro, T.A.; Fahey, J.W.; Wade, K.L.; Stephenson, K.K.; Talalay, P. Human metabolism and excretion of cancer chemoprotective glucosinolates and isothiocyanates of cruciferous vegetables. Cancer Epidemiol. Biomarkers Prev., 1998, 7(12), 1091-1100.
[PMID: 9865427]
[7]
Willett, W.C. Diet and cancer: One view at the start of the millennium. Cancer Epidemiol. Biomarkers Prev., 2001, 10(1), 3-8.
[PMID: 11205486]
[8]
Tse, G.; Eslick, G.D. Cruciferous vegetables and risk of colorectal neoplasms: A systematic review and meta-analysis. Nutr. Cancer, 2014, 66(1), 128-139.
[http://dx.doi.org/10.1080/01635581.2014.852686] [PMID: 24341734]
[9]
Rao, C.V. Benzyl isothiocyanate: Double trouble for breast cancer cells. Cancer Prev. Res. (Phila.), 2013, 6(8), 760-763.
[http://dx.doi.org/10.1158/1940-6207.CAPR-13-0242] [PMID: 23842793]
[10]
Houghton, C.A.; Fassett, R.G.; Coombes, J.S. Sulforaphane: Translational research from laboratory bench to clinic. Nutr. Rev., 2013, 71(11), 709-726.
[http://dx.doi.org/10.1111/nure.12060] [PMID: 24147970]
[11]
Atwell, L.L.; Hsu, A.; Wong, C.P.; Stevens, J.F.; Bella, D.; Yu, T.W.; Pereira, C.B.; Löhr, C.V.; Christensen, J.M.; Dashwood, R.H.; Williams, D.E.; Shannon, J.; Ho, E. Absorption and chemopreventive targets of sulforaphane in humans following consumption of broccoli sprouts or a myrosinase-treated broccoli sprout extract. Mol. Nutr. Food Res., 2015, 59(3), 424-433.
[http://dx.doi.org/10.1002/mnfr.201400674] [PMID: 25522265]
[12]
Cornblatt, B.S.; Ye, L.; Dinkova-Kostova, A.T.; Erb, M.; Fahey, J.W.; Singh, N.K.; Chen, M.S.; Stierer, T.; Garrett-Mayer, E.; Argani, P.; Davidson, N.E.; Talalay, P.; Kensler, T.W.; Visvanathan, K. Preclinical and clinical evaluation of sulforaphane for chemoprevention in the breast. Carcinogenesis, 2007, 28(7), 1485-1490.
[http://dx.doi.org/10.1093/carcin/bgm049] [PMID: 17347138]
[13]
Terry, P.; Wolk, A.; Persson, I.; Magnusson, C. Brassica vegetables and breast cancer risk. JAMA, 2001, 285(23), 2975-2977.
[http://dx.doi.org/10.1001/jama.285.23.2975] [PMID: 11410091]
[14]
Ambrosone, C.B.; McCann, S.E.; Freudenheim, J.L.; Marshall, J.R.; Zhang, Y.; Shields, P.G. Breast cancer risk in premenopausal women is inversely associated with consumption of broccoli, a source of isothiocyanates, but is not modified by GST genotype. J. Nutr., 2004, 134(5), 1134-1138.
[http://dx.doi.org/10.1093/jn/134.5.1134] [PMID: 15113959]
[15]
Liu, X.; Lv, K. Cruciferous vegetables intake is inversely associated with risk of breast cancer: A meta-analysis. Breast, 2013, 22(3), 309-313.
[http://dx.doi.org/10.1016/j.breast.2012.07.013] [PMID: 22877795]
[16]
Ngo, S.N.T. Are isothiocyanates from cruciferous vegetables potential therapeutic agents for breast cancer. Int. J. Biol. Eng., 2016, 6, 7-11.
[17]
Australian Institute of Health and Welfare (AIHW). Australia’s health, 2012. http://www.aihw.gov.au/publications (Accessed Dec 19, 2019).
[18]
Grayson, M. Breast cancer. Nature, 2012, 485(7400), S49.
[http://dx.doi.org/10.1038/485S49a] [PMID: 22648496]
[19]
Atwell, L.L.; Zhang, Z.; Mori, M.; Farris, P.; Vetto, J.T.; Naik, A.M.; Oh, K.Y.; Thuillier, P.; Ho, E.; Shannon, J. Sulforaphane bioavailability and chemopreventive activity in women scheduled for breast biopsy. Cancer Prev. Res. (Phila.), 2015, 8(12), 1184-1191.
[http://dx.doi.org/10.1158/1940-6207.CAPR-15-0119] [PMID: 26511489]
[20]
Thomson, C.A.; Rock, C.L.; Thompson, P.A.; Caan, B.J.; Cussler, E.; Flatt, S.W.; Pierce, J.P. Vegetable intake is associated with reduced breast cancer recurrence in tamoxifen users: A secondary analysis from the Women’s Healthy Eating and Living Study. Breast Cancer Res. Treat., 2011, 125(2), 519-527.
[http://dx.doi.org/10.1007/s10549-010-1014-9] [PMID: 20607600]
[21]
Boggs, D.A.; Palmer, J.R.; Wise, L.A.; Spiegelman, D.; Stampfer, M.J.; Adams-Campbell, L.L.; Rosenberg, L. Fruit and vegetable intake in relation to risk of breast cancer in the Black Women’s Health Study. Am. J. Epidemiol., 2010, 172(11), 1268-1279.
[http://dx.doi.org/10.1093/aje/kwq293] [PMID: 20937636]
[22]
Nechuta, S.; Caan, B.J.; Chen, W.Y.; Kwan, M.L.; Lu, W.; Cai, H.; Poole, E.M.; Flatt, S.W.; Zheng, W.; Pierce, J.P.; Shu, X.O. Postdiagnosis cruciferous vegetable consumption and breast cancer outcomes: a report from the After Breast Cancer Pooling Project. Cancer Epidemiol. Biomarkers Prev., 2013, 22(8), 1451-1456.
[http://dx.doi.org/10.1158/1055-9965.EPI-13-0446] [PMID: 23765086]
[23]
Beasley, J.M.; Newcomb, P.A.; Trentham-Dietz, A.; Hampton, J.M.; Bersch, A.J.; Passarelli, M.N.; Holick, C.N.; Titus-Ernstoff, L.; Egan, K.M.; Holmes, M.D.; Willett, W.C. Post-diagnosis dietary factors and survival after invasive breast cancer. Breast Cancer Res. Treat., 2011, 128(1), 229-236.
[http://dx.doi.org/10.1007/s10549-010-1323-z] [PMID: 21197569]
[24]
Zhang, Z.; Atwell, L.L.; Farris, P.E.; Ho, E.; Shannon, J. Associations between cruciferous vegetable intake and selected biomarkers among women scheduled for breast biopsies. Public Health Nutr., 2016, 19(7), 1288-1295.
[http://dx.doi.org/10.1017/S136898001500244X] [PMID: 26329135]
[25]
Zhang, C.X.; Ho, S.C.; Chen, Y.M.; Fu, J.H.; Cheng, S.Z.; Lin, F.Y. Greater vegetable and fruit intake is associated with a lower risk of breast cancer among Chinese women. Int. J. Cancer, 2009, 125(1), 181-188.
[http://dx.doi.org/10.1002/ijc.24358] [PMID: 19358284]
[26]
Lee, S.A.; Fowke, J.H.; Lu, W.; Ye, C.; Zheng, Y.; Cai, Q.; Gu, K.; Gao, Y.T.; Shu, X.O.; Zheng, W. Cruciferous vegetables, the GSTP1 Ile105Val genetic polymorphism, and breast cancer risk. Am. J. Clin. Nutr., 2008, 87(3), 753-760.
[http://dx.doi.org/10.1093/ajcn/87.3.753] [PMID: 18326615]
[27]
Shannon, J.; Ray, R.; Wu, C.; Nelson, Z.; Gao, D.L.; Li, W.; Hu, W.; Lampe, J.; Horner, N.; Satia, J.; Patterson, R.; Fitzgibbons, D.; Porter, P.; Thomas, D. Food and botanical groupings and risk of breast cancer: A case-control study in Shanghai, China. Cancer Epidemiol. Biomarkers Prev., 2005, 14(1), 81-90.
[PMID: 15668480]
[28]
Graham, S.; Marshall, J.; Mettlin, C.; Rzepka, T.; Nemoto, T.; Byers, T. Diet in the epidemiology of breast cancer. Am. J. Epidemiol., 1982, 116(1), 68-75.
[http://dx.doi.org/10.1093/oxfordjournals.aje.a113403] [PMID: 7102657]
[29]
Katsouyanni, K.; Trichopoulos, D.; Boyle, P.; Xirouchaki, E.; Trichopoulou, A.; Lisseos, B.; Vasilaros, S.; MacMahon, B. Diet and breast cancer: A case-control study in Greece. Int. J. Cancer, 1986, 38(6), 815-820.
[http://dx.doi.org/10.1002/ijc.2910380606] [PMID: 3793261]
[30]
Fink, B.N.; Gaudet, M.M.; Britton, J.A.; Abrahamson, P.E.; Teitelbaum, S.L.; Jacobson, J.; Bell, P.; Thomas, J.A.; Kabat, G.C.; Neugut, A.I.; Gammon, M.D. Fruits, vegetables, and micronutrient intake in relation to breast cancer survival. Breast Cancer Res. Treat., 2006, 98(2), 199-208.
[http://dx.doi.org/10.1007/s10549-005-9150-3] [PMID: 16538530]
[31]
Gaudet, M.M.; Britton, J.A.; Kabat, G.C.; Steck-Scott, S.; Eng, S.M.; Teitelbaum, S.L.; Terry, M.B.; Neugut, A.I.; Gammon, M.D. Fruits, vegetables, and micronutrients in relation to breast cancer modified by menopause and hormone receptor status. Cancer Epidemiol. Biomarkers Prev., 2004, 13(9), 1485-1494.
[PMID: 15342450]
[32]
Steck, S.E.; Gaudet, M.M.; Britton, J.A.; Teitelbaum, S.L.; Terry, M.B.; Neugut, A.I.; Santella, R.M.; Gammon, M.D. Interactions among GSTM1, GSTT1 and GSTP1 polymorphisms, cruciferous vegetable intake and breast cancer risk. Carcinogenesis, 2007, 28(9), 1954-1959.
[http://dx.doi.org/10.1093/carcin/bgm141] [PMID: 17693660]
[33]
Kanematsu, S.; Yoshizawa, K.; Uehara, N.; Miki, H.; Sasaki, T.; Kuro, M.; Lai, Y.C.; Kimura, A.; Yuri, T.; Tsubura, A. Sulforaphane inhibits the growth of KPL-1 human breast cancer cells in vitro and suppresses the growth and metastasis of orthotopically transplanted KPL-1 cells in female athymic mice. Oncol. Rep., 2011, 26(3), 603-608.
[PMID: 21617865]
[34]
Li, Y.; Zhang, T.; Korkaya, H.; Liu, S.; Lee, H.F.; Newman, B.; Yu, Y.; Clouthier, S.G.; Schwartz, S.J.; Wicha, M.S.; Sun, D. Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. Clin. Cancer Res., 2010, 16(9), 2580-2590.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-2937] [PMID: 20388854]
[35]
Warin, R.; Xiao, D.; Arlotti, J.A.; Bommareddy, A.; Singh, S.V. Inhibition of human breast cancer xenograft growth by cruciferous vegetable constituent benzyl isothiocyanate. Mol. Carcinog., 2010, 49(5), 500-507.
[http://dx.doi.org/10.1002/mc.20600] [PMID: 20422714]
[36]
Gupta, P.; Adkins, C.; Lockman, P.; Srivastava, S.K. Metastasis of breast tumor cells to brain is suppressed by phenethyl isothiocyanate in a novel in vivo metastasis model. PLoS One, 2013, 8(6), e67278.
[http://dx.doi.org/10.1371/journal.pone.0067278] [PMID: 23826254]
[37]
Hussain, A.; Mohsin, J.; Prabhu, S.A.; Begum, S. Nusri, Qel-A.; Harish, G.; Javed, E.; Khan, M.A.; Sharma, C. Sulforaphane inhibits growth of human breast cancer cells and augments the therapeutic index of the chemotherapeutic drug, gemcitabine. Asian Pac. J. Cancer Prev., 2013, 14(10), 5855-5860.
[http://dx.doi.org/10.7314/APJCP.2013.14.10.5855] [PMID: 24289589]
[38]
Li, Q.; Xia, J.; Yao, Y.; Gong, D.W.; Shi, H.; Zhou, Q. Sulforaphane inhibits mammary adipogenesis by targeting adipose mesenchymal stem cells. Breast Cancer Res. Treat., 2013, 141(2), 317-324.
[http://dx.doi.org/10.1007/s10549-013-2672-1] [PMID: 24002734]
[39]
Lee, Y.R.; Noh, E.M.; Han, J.H.; Kim, J.M.; Hwang, B.M.; Kim, B.S.; Lee, S.H.; Jung, S.H.; Youn, H.J.; Chung, E.Y.; Kim, J.S. Sulforaphane controls TPA-induced MMP-9 expression through the NF-κB signaling pathway, but not AP-1, in MCF-7 breast cancer cells. BMB Rep., 2013, 46(4), 201-206.
[http://dx.doi.org/10.5483/BMBRep.2013.46.4.160] [PMID: 23615261]
[40]
Pawlik, A.; Wiczk, A.; Kaczyńska, A.; Antosiewicz, J.; Herman-Antosiewicz, A. Sulforaphane inhibits growth of phenotypically different breast cancer cells. Eur. J. Nutr., 2013, 52(8), 1949-1958.
[http://dx.doi.org/10.1007/s00394-013-0499-5] [PMID: 23389114]
[41]
Sarkar, R.; Mukherjee, S.; Biswas, J.; Roy, M. Sulphoraphane, a naturally occurring isothiocyanate induces apoptosis in breast cancer cells by targeting heat shock proteins. Biochem. Biophys. Res. Commun., 2012, 427(1), 80-85.
[http://dx.doi.org/10.1016/j.bbrc.2012.09.006] [PMID: 22975350]
[42]
Kanematsu, S.; Uehara, N.; Miki, H.; Yoshizawa, K.; Kawanaka, A.; Yuri, T.; Tsubura, A. Autophagy inhibition enhances sulforaphane-induced apoptosis in human breast cancer cells. Anticancer Res., 2010, 30(9), 3381-3390.
[PMID: 20944112]
[43]
Meeran, S.M.; Patel, S.N.; Tollefsbol, T.O. Sulforaphane causes epigenetic repression of hTERT expression in human breast cancer cell lines. PLoS One, 2010, 5(7), e11457.
[http://dx.doi.org/10.1371/journal.pone.0011457] [PMID: 20625516]
[44]
Hunakova, L.; Sedlakova, O.; Cholujova, D.; Gronesova, P.; Duraj, J.; Sedlak, J. Modulation of markers associated with aggressive phenotype in MDA-MB-231 breast carcinoma cells by sulforaphane. Neoplasma, 2009, 56(6), 548-556.
[http://dx.doi.org/10.4149/neo_2009_06_548] [PMID: 19728765]
[45]
Ramirez, M.C.; Singletary, K. Regulation of estrogen receptor alpha expression in human breast cancer cells by sulforaphane. J. Nutr. Biochem., 2009, 20(3), 195-201.
[http://dx.doi.org/10.1016/j.jnutbio.2008.02.002] [PMID: 18602823]
[46]
Telang, U.; Brazeau, D.A.; Morris, M.E. Comparison of the effects of phenethyl isothiocyanate and sulforaphane on gene expression in breast cancer and normal mammary epithelial cells. Exp. Biol. Med. (Maywood), 2009, 234(3), 287-295.
[http://dx.doi.org/10.3181/0808-RM-241] [PMID: 19144873]
[47]
Azarenko, O.; Okouneva, T.; Singletary, K.W.; Jordan, M.A.; Wilson, L. Suppression of microtubule dynamic instability and turnover in MCF7 breast cancer cells by sulforaphane. Carcinogenesis, 2008, 29(12), 2360-2368.
[http://dx.doi.org/10.1093/carcin/bgn241] [PMID: 18952594]
[48]
Jo, E.H.; Kim, S.H.; Ahn, N.S.; Park, J.S.; Hwang, J.W.; Lee, Y.S.; Kang, K.S. Efficacy of sulforaphane is mediated by p38 MAP kinase and caspase-7 activations in ER-positive and COX-2-expressed human breast cancer cells. Eur. J. Cancer Prev., 2007, 16(6), 505-510.
[http://dx.doi.org/10.1097/01.cej.0000243856.97479.3b] [PMID: 18090122]
[49]
Pledgie-Tracy, A.; Sobolewski, M.D.; Davidson, N.E. Sulforaphane induces cell type-specific apoptosis in human breast cancer cell lines. Mol. Cancer Ther., 2007, 6(3), 1013-1021.
[http://dx.doi.org/10.1158/1535-7163.MCT-06-0494] [PMID: 17339367]
[50]
Wang, W.; Wang, S.; Howie, A.F.; Beckett, G.J.; Mithen, R.; Bao, Y. Sulforaphane, erucin, and iberin up-regulate thioredoxin reductase 1 expression in human MCF-7 cells. J. Agric. Food Chem., 2005, 53(5), 1417-1421.
[http://dx.doi.org/10.1021/jf048153j] [PMID: 15740016]
[51]
Jackson, S.J.; Singletary, K.W. Sulforaphane inhibits human MCF-7 mammary cancer cell mitotic progression and tubulin polymerization. J. Nutr., 2004, 134(9), 2229-2236.
[http://dx.doi.org/10.1093/jn/134.9.2229] [PMID: 15333709]
[52]
Tseng, E.; Scott-Ramsay, E.A.; Morris, M.E. Dietary organic isothiocyanates are cytotoxic in human breast cancer MCF-7 and mammary epithelial MCF-12A cell lines. Exp. Biol. Med. (Maywood), 2004, 229(8), 835-842.
[http://dx.doi.org/10.1177/153537020422900817] [PMID: 15337839]
[53]
Kim, S.H.; Sehrawat, A.; Singh, S.V. Dietary chemopreventative benzyl isothiocyanate inhibits breast cancer stem cells in vitro and in vivo. Cancer Prev. Res. (Phila.), 2013, 6(8), 782-790.
[http://dx.doi.org/10.1158/1940-6207.CAPR-13-0100] [PMID: 23661606]
[54]
Sehrawat, A.; Kim, S.H.; Vogt, A.; Singh, S.V. Suppression of FOXQ1 in benzyl isothiocyanate-mediated inhibition of epithelial-mesenchymal transition in human breast cancer cells. Carcinogenesis, 2013, 34(4), 864-873.
[http://dx.doi.org/10.1093/carcin/bgs397] [PMID: 23276794]
[55]
Kim, S.H.; Sehrawat, A.; Singh, S.V. Notch2 activation by benzyl isothiocyanate impedes its inhibitory effect on breast cancer cell migration. Breast Cancer Res. Treat., 2012, 134(3), 1067-1079.
[http://dx.doi.org/10.1007/s10549-012-2043-3] [PMID: 22476855]
[56]
Xiao, D.; Bommareddy, A.; Kim, S.H.; Sehrawat, A.; Hahm, E.R.; Singh, S.V. Benzyl isothiocyanate causes FoxO1-mediated autophagic death in human breast cancer cells. PLoS One, 2012, 7(3), e32597.
[http://dx.doi.org/10.1371/journal.pone.0032597] [PMID: 22457718]
[57]
Kim, E.J.; Eom, S.J.; Hong, J.E.; Lee, J.Y.; Choi, M.S.; Park, J.H. Benzyl isothiocyanate inhibits basal and hepatocyte growth factor-stimulated migration of breast cancer cells. Mol. Cell. Biochem., 2012, 359(1-2), 431-440.
[http://dx.doi.org/10.1007/s11010-011-1039-3] [PMID: 21892609]
[58]
Antony, M.L.; Kim, S.H.; Singh, S.V. Critical role of p53 upregulated modulator of apoptosis in benzyl isothiocyanate-induced apoptotic cell death. PLoS One, 2012, 7(2), e32267.
[http://dx.doi.org/10.1371/journal.pone.0032267] [PMID: 22359675]
[59]
Sehrawat, A.; Singh, S.V. Benzyl isothiocyanate inhibits epithelial-mesenchymal transition in cultured and xenografted human breast cancer cells. Cancer Prev. Res. (Phila.), 2011, 4(7), 1107-1117.
[http://dx.doi.org/10.1158/1940-6207.CAPR-10-0306] [PMID: 21464039]
[60]
Kim, S-H.; Nagalingam, A.; Saxena, N.K.; Singh, S.V.; Sharma, D. Benzyl isothiocyanate inhibits oncogenic actions of leptin in human breast cancer cells by suppressing activation of signal transducer and activator of transcription 3. Carcinogenesis, 2011, 32(3), 359-367.
[http://dx.doi.org/10.1093/carcin/bgq267] [PMID: 21163886]
[61]
Kim, S.H.; Singh, S.V. p53-Independent apoptosis by benzyl isothiocyanate in human breast cancer cells is mediated by suppression of XIAP expression. Cancer Prev. Res. (Phila.), 2010, 3(6), 718-726.
[http://dx.doi.org/10.1158/1940-6207.CAPR-10-0048] [PMID: 20484174]
[62]
Kang, L.; Ding, L.; Wang, Z.Y. Isothiocyanates repress estrogen receptor alpha expression in breast cancer cells. Oncol. Rep., 2009, 21(1), 185-192.
[PMID: 19082460]
[63]
Xiao, D.; Powolny, A.A.; Singh, S.V. Benzyl isothiocyanate targets mitochondrial respiratory chain to trigger reactive oxygen species-dependent apoptosis in human breast cancer cells. J. Biol. Chem., 2008, 283(44), 30151-30163.
[http://dx.doi.org/10.1074/jbc.M802529200] [PMID: 18768478]
[64]
Xiao, D.; Vogel, V.; Singh, S.V. Benzyl isothiocyanate-induced apoptosis in human breast cancer cells is initiated by reactive oxygen species and regulated by Bax and Bak. Mol. Cancer Ther., 2006, 5(11), 2931-2945.
[http://dx.doi.org/10.1158/1535-7163.MCT-06-0396] [PMID: 17121941]
[65]
Cang, S.; Ma, Y.; Chiao, J.W.; Liu, D. Phenethyl isothiocyanate and paclitaxel synergistically enhanced apoptosis and alpha-tubulin hyperacetylation in breast cancer cells. Exp. Hematol. Oncol., 2014, 3(1), 5.
[http://dx.doi.org/10.1186/2162-3619-3-5] [PMID: 24495785]
[66]
Sakao, K.; Hahm, E.R.; Singh, S.V. In vitro and in vivo effects of phenethyl isothiocyanate treatment on vimentin protein expression in cancer cells. Nutr. Cancer, 2013, 65(Suppl. 1), 61-67.
[http://dx.doi.org/10.1080/01635581.2013.785002] [PMID: 23682784]
[67]
Liu, K.; Cang, S.; Ma, Y.; Chiao, J.W. Synergistic effect of paclitaxel and epigenetic agent phenethyl isothiocyanate on growth inhibition, cell cycle arrest and apoptosis in breast cancer cells. Cancer Cell Int., 2013, 13(1), 10.
[http://dx.doi.org/10.1186/1475-2867-13-10] [PMID: 23388416]
[68]
Sarkars, R.; Mukherjee, S.; Roy, M. Targeting heat shock proteins by phenethyl isothiocyanate results in cell-cycle arrest and apoptosis of human breast cancer cells. Nutr. Cancer, 2013, 65(3), 480-493.
[http://dx.doi.org/10.1080/01635581.2013.767366] [PMID: 23530648]
[69]
Gupta, P.; Srivastava, S.K. Antitumor activity of phenethyl isothiocyanate in HER2-positive breast cancer models. BMC Med., 2012, 10, 80.
[http://dx.doi.org/10.1186/1741-7015-10-80] [PMID: 22824293]
[70]
Syed Alwi, S.S.; Cavell, B.E.; Donlevy, A.; Packham, G.; Packham, G. Differential induction of apoptosis in human breast cancer cell lines by phenethyl isothiocyanate, a glutathione depleting agent. Cell Stress Chaperones, 2012, 17(5), 529-538.
[http://dx.doi.org/10.1007/s12192-012-0329-3] [PMID: 22351438]
[71]
Hahm, E.R.; Singh, S.V. Bim contributes to phenethyl isothiocyanate-induced apoptosis in breast cancer cells. Mol. Carcinog., 2012, 51(6), 465-474.
[http://dx.doi.org/10.1002/mc.20811] [PMID: 21739479]
[72]
Moon, Y.J.; Brazeau, D.A.; Morris, M.E. Dietary phenethyl isothiocyanate alters gene expression in human breast cancer cells. Evid. Based Complement. Alternat. Med., 2011, 2011, Article ID 462525.
[http://dx.doi.org/10.1155/2011/462525]
[73]
Kang, L.; Wang, Z.Y.J. Breast cancer cell growth inhibition by phenethyl isothiocyanate is associated with down-regulation of oestrogen receptor-alpha36. J. Cell. Mol. Med., 2010, 14(6B), 1485-1493.
[http://dx.doi.org/10.1111/j.1582-4934.2009.00877.x] [PMID: 19840189]
[74]
Lee, J.W.; Cho, M.K. Phenethyl isothiocyanate induced apoptosis via down regulation of Bcl-2/XIAP and triggering of the mitochondrial pathway in MCF-7 cells. Arch. Pharm. Res., 2008, 31(12), 1604-1612.
[http://dx.doi.org/10.1007/s12272-001-2158-2] [PMID: 19099231]
[75]
Koschorke, A.; Faraci, S.; Giani, D.; Chiodoni, C.; Iorio, E.; Canese, R.; Colombo, M.P.; Lamolinara, A.; Iezzi, M.; Ladomery, M.; Vernieri, C.; de Braud, F.; Di Nicola, M.; Tagliabue, E.; Castagnoli, L.; Pupa, S.M. Phenethyl isothiocyanate hampers growth and progression of HER2-positive breast and ovarian carcinoma by targeting their stem cell compartment. Cell Oncol. (Dordr.), 2019, 42(6), 815-828.
[http://dx.doi.org/10.1007/s13402-019-00464-w] [PMID: 31376137]
[76]
Nguyen, Y.T.; Moon, J.Y.; Ediriweera, M.K.; Cho, S.K. Phenethyl isothiocyanate suppresses stemness in the chemo- and radio-resistant triple-negative breast cancer cell line MDA-MB-231/IR via downregulation of metadherin. Cancers (Basel), 2020, 12(2), E268.
[http://dx.doi.org/10.3390/cancers12020268] [PMID: 31979093]
[77]
Cheng, A-C.; Shen, C-J.; Hung, C-M.; Hsu, Y-C. Sulforaphane decrease of SERTAD1 expression triggers G1/S arrest in breast cancer cells. J. Med. Food, 2019, 22(5), 444-450.
[http://dx.doi.org/10.1089/jmf.2018.4195] [PMID: 31084542]
[78]
Roy, R.; Hahm, E.R.; White, A.G.; Anderson, C.J.; Singh, S.V. AKT-dependent sugar addiction by benzyl isothiocyanate in breast cancer cells. Mol. Carcinog., 2019, 58(6), 996-1007.
[http://dx.doi.org/10.1002/mc.22988] [PMID: 30720225]
[79]
Kim, S.H.; Singh, S.V. Role of Krüppel-like factor 4-p21CIP1 axis in breast cancer stem-like cell inhibition by benzyl isothiocyanate. Cancer Prev. Res. (Phila.), 2019, 12(3), 125-134.
[http://dx.doi.org/10.1158/1940-6207.CAPR-18-0393] [PMID: 30723175]
[80]
Abdull Razis, A.F.; Noor, N.M. Cruciferous vegetables: Dietary phytochemicals for cancer prevention. Asian Pac. J. Cancer Prev., 2013, 14(3), 1565-1570.
[http://dx.doi.org/10.7314/APJCP.2013.14.3.1565] [PMID: 23679237]
[81]
Tang, L.; Paonessa, J.D.; Zhang, Y.; Ambrosone, C.B.; McCann, S.E. Total isothiocyanate yield from raw cruciferous vegetables commonly consumed in the United States. J. Funct. Foods, 2013, 5(4), 1996-2001.
[http://dx.doi.org/10.1016/j.jff.2013.07.011] [PMID: 24443655]
[82]
Clarke, J.D.; Hsu, A.; Riedl, K.; Bella, D.; Schwartz, S.J.; Stevens, J.F.; Ho, E. Bioavailability and inter-conversion of sulforaphane and erucin in human subjects consuming broccoli sprouts or broccoli supplement in a cross-over study design. Pharmacol. Res., 2011, 64(5), 456-463.
[http://dx.doi.org/10.1016/j.phrs.2011.07.005] [PMID: 21816223]
[83]
Ye, L.; Dinkova-Kostova, A.T.; Wade, K.L.; Zhang, Y.; Shapiro, T.A.; Talalay, P. Quantitative determination of dithiocarbamates in human plasma, serum, erythrocytes and urine: pharmacokinetics of broccoli sprout isothiocyanates in humans. Clin. Chim. Acta, 2002, 316(1-2), 43-53.
[http://dx.doi.org/10.1016/S0009-8981(01)00727-6] [PMID: 11750273]
[84]
Shapiro, T.A.; Fahey, J.W.; Dinkova-Kostova, A.T.; Holtzclaw, W.D.; Stephenson, K.K.; Wade, K.L.; Ye, L.; Talalay, P. Safety, tolerance, and metabolism of broccoli sprout glucosinolates and isothiocyanates: A clinical phase I study. Nutr. Cancer, 2006, 55(1), 53-62.
[http://dx.doi.org/10.1207/s15327914nc5501_7] [PMID: 16965241]
[85]
Egner, P.A.; Chen, J.G.; Wang, J.B.; Wu, Y.; Sun, Y.L.; Lu, J.H.; Zhu, J.; Zhang, Y.H.; Chen, Y.S.; Friesen, M.D.; Jacobson, L.P.; Muñoz, A.; Ng, D.; Qian, G.S.; Zhu, Y.R.; Chen, T.Y.; Botting, N.P.; Zhang, Q.; Fahey, J.W.; Talalay, P.; Groopman, J.D.; Kensler, T.W. Bioavailability of sulforaphane from two broccoli sprout beverages: Results of a short-term, cross-over clinical trial in Qidong, China. Cancer Prev. Res. (Phila.), 2011, 4(3), 4384-4395.
[86]
Cramer, J.M.; Jeffery, E.H. Sulforaphane absorption and excretion following ingestion of a semi-purified broccoli powder rich in glucoraphanin and broccoli sprouts in healthy men. Nutr. Cancer, 2011, 63(2), 196-201.
[http://dx.doi.org/10.1080/01635581.2011.523495] [PMID: 21240766]
[87]
West, L.G.; Meyer, K.A.; Balch, B.A.; Rossi, F.J.; Schultz, M.R.; Haas, G.W. Glucoraphanin and 4-hydroxyglucobrassicin contents in seeds of 59 cultivars of broccoli, raab, kohlrabi, radish, cauliflower, brussels sprouts, kale, and cabbage. J. Agric. Food Chem., 2004, 52(4), 916-926.
[http://dx.doi.org/10.1021/jf0307189] [PMID: 14969551]
[88]
Bahadoran, Z.; Mirmiran, P.; Hosseinpanah, F.; Hedayati, M.; Hosseinpour-Niazi, S.; Azizi, F. Broccoli sprouts reduce oxidative stress in type 2 diabetes: A randomized double-blind clinical trial. Eur. J. Clin. Nutr., 2011, 65(8), 972-977.
[http://dx.doi.org/10.1038/ejcn.2011.59] [PMID: 21559038]
[89]
Galan, M.V.; Kishan, A.A.; Silverman, A.L. Oral broccoli sprouts for the treatment of Helicobacter pylori infection: A preliminary report. Dig. Dis. Sci., 2004, 49(7-8), 1088-1090.
[http://dx.doi.org/10.1023/B:DDAS.0000037792.04787.8a] [PMID: 15387326]
[90]
Murashima, M.; Watanabe, S.; Zhuo, X.G.; Uehara, M.; Kurashige, A. Phase 1 study of multiple biomarkers for metabolism and oxidative stress after one-week intake of broccoli sprouts. Biofactors, 2004, 22(1-4), 271-275.
[http://dx.doi.org/10.1002/biof.5520220154] [PMID: 15630296]
[91]
Myzak, M.C.; Tong, P.; Dashwood, W-M.; Dashwood, R.H.; Ho, E. Sulforaphane retards the growth of human PC-3 xenografts and inhibits HDAC activity in human subjects. Exp. Biol. Med. (Maywood), 2007, 232(2), 227-234.
[PMID: 17259330]
[92]
Riedl, M.A.; Saxon, A.; Diaz-Sanchez, D. Oral sulforaphane increases Phase II antioxidant enzymes in the human upper airway. Clin. Immunol., 2009, 130(3), 244-251.
[http://dx.doi.org/10.1016/j.clim.2008.10.007] [PMID: 19028145]
[93]
Yanaka, A.; Fahey, J.W.; Fukumoto, A.; Nakayama, M.; Inoue, S.; Zhang, S.; Tauchi, M.; Suzuki, H.; Hyodo, I.; Yamamoto, M. Dietary sulforaphane-rich broccoli sprouts reduce colonization and attenuate gastritis in Helicobacter pylori-infected mice and humans. Cancer Prev. Res. (Phila.), 2009, 2(4), 353-360.
[http://dx.doi.org/10.1158/1940-6207.CAPR-08-0192] [PMID: 19349290]
[94]
Bahadoran, Z.; Mirmiran, P.; Hosseinpanah, F.; Rajab, A.; Asghari, G.; Azizi, F. Broccoli sprouts powder could improve serum triglyceride and oxidized LDL/LDL-cholesterol ratio in type 2 diabetic patients: A randomized double-blind placebo-controlled clinical trial. Diabetes Res. Clin. Pract., 2012, 96(3), 348-354.
[http://dx.doi.org/10.1016/j.diabres.2012.01.009] [PMID: 22325157]
[95]
Clarke, J.D.; Riedl, K.; Bella, D.; Schwartz, S.J.; Stevens, J.F.; Ho, E. Comparison of isothiocyanate metabolite levels and histone deacetylase activity in human subjects consuming broccoli sprouts or broccoli supplement. J. Agric. Food Chem., 2011, 59(20), 10955-10963.
[http://dx.doi.org/10.1021/jf202887c] [PMID: 21928849]
[96]
Fahey, J.W.; Kensler, T.W. Role of dietary supplements/nutraceuticals in chemoprevention through induction of cytoprotective enzymes. Chem. Res. Toxicol., 2007, 20(4), 572-576.
[http://dx.doi.org/10.1021/tx7000459] [PMID: 17362031]
[97]
Fahey, J.W.; Zhang, Y.; Talalay, P. Broccoli sprouts: An exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proc. Natl. Acad. Sci. USA, 1997, 94(19), 10367-10372.
[http://dx.doi.org/10.1073/pnas.94.19.10367] [PMID: 9294217]
[98]
Bekaert, M.; Edger, P.P.; Hudson, C.M.; Pires, J.C.; Conant, G.C. Metabolic and evolutionary costs of herbivory defense: Systems biology of glucosinolate synthesis. New Phytol., 2012, 196(2), 596-605.
[http://dx.doi.org/10.1111/j.1469-8137.2012.04302.x] [PMID: 22943527]
[99]
Zhang, Y.; Talalay, P.; Cho, C.G.; Posner, G.H. A major inducer of anticarcinogenic protective enzymes from broccoli: Isolation and elucidation of structure. Proc. Natl. Acad. Sci. USA, 1992, 89(6), 2399-2403.
[http://dx.doi.org/10.1073/pnas.89.6.2399] [PMID: 1549603]
[100]
Kensler, T.W.; Chen, J.G.; Egner, P.A.; Fahey, J.W.; Jacobson, L.P.; Stephenson, K.K.; Ye, L.; Coady, J.L.; Wang, J.B.; Wu, Y.; Sun, Y.; Zhang, Q.N.; Zhang, B.C.; Zhu, Y.R.; Qian, G.S.; Carmella, S.G.; Hecht, S.S.; Benning, L.; Gange, S.J.; Groopman, J.D.; Talalay, P. 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 Epidemiol. Biomarkers Prev., 2005, 14(11 Pt 1), 2605-2613.
[http://dx.doi.org/10.1158/1055-9965.EPI-05-0368] [PMID: 16284385]
[101]
Kamal, M.M.; Akter, S.; Lin, C.N.; Nazzal, S. Sulforaphane as an anticancer molecule: Mechanisms of action, synergistic effects, enhancement of drug safety, and delivery systems. Arch. Pharm. Res., 2020, 43(4), 371-384.
[http://dx.doi.org/10.1007/s12272-020-01225-2] [PMID: 32152852]

Rights & Permissions Print Cite
Article Metrics
48
1
© 2024 Bentham Science Publishers | Privacy Policy