萝卜硫素在乳腺癌、卵巢癌及宫颈癌中的潜在作用

张维; 李苏宜

doi:10.16689/j.cnki.cn11-9349/r.2020.04.003

PDF(443 KB)

肿瘤代谢与营养电子杂志 ›› 2020, Vol. 7 ›› Issue (4) : 391-395. DOI: 10.16689/j.cnki.cn11-9349/r.2020.04.003

全民健康助力全面小康

萝卜硫素在乳腺癌、卵巢癌及宫颈癌中的潜在作用

张维1，李苏宜2

作者信息 +

The potential role of sulforaphane in breast cancer, ovarian cancer and cervical cancer

Zhang Wei1, Li Suyi2

Author information +

文章历史 +

摘要

随着医学对硫代葡萄糖苷在植物中积累的遗传和环境因素的了解以及对这些化合物及其衍生物作用认识的增加，人们对硫代葡萄糖苷及其产物可能的作用研究也有了重大进展，作为饮食的一部分时，其可以降低肿瘤和心脏病的风险。研究发现，这些生物活性物质与传统的抗肿瘤治疗方法结合起来，可以提高抗肿瘤治疗的效果。萝卜硫素是一种同源异硫氰酸酯，主要存在于芸薹属蔬菜中，其摄入与乳腺癌、卵巢癌等肿瘤的发生呈显著负相关，可能是通过提高细胞的解毒能力和抗氧化能力外，萝卜硫素还可以调节细胞的生长，这对于肿瘤预防尤其重要。萝卜硫素的细胞抑制和细胞毒性作用机制包括诱导细胞凋亡、抑制细胞周期进程和抑制血管生成，靶向肿瘤细胞关键细胞信号通路的多个位点，发挥类似靶向药物的抗肿瘤作用。本篇综述通过介绍萝卜硫素在乳腺癌、卵巢癌及宫颈癌辅助化疗和放疗疗效的可能机制，为其在乳腺癌、卵巢癌及宫颈癌临床上的应用提供理论线索。

Abstract

As our understanding of the genetic and environmental factors that glucosinolates accumulate in plants and the effects of these compounds and their derivatives has increased, so has our understanding of the role glucosinolates and their products may play in reducing the risk of cancer and heart disease when consumed as part of a diet. After absorption and distribution in the body, they will affect the general defensive mechanisms of the body, including the prevention and treatment of tumors.It has been found that the combination of these bioactive substances with traditional anti-tumor therapies can improve the effectiveness of anti-tumor therapy.Sulforaphane is a homologous isothiocyanate mainly found in brassica vegetables.Evidence shows that the intake of sulforaphane is significantly negatively correlated with cancers such as breast cancer and ovarian cancer. It may be that sulforaphane can regulate cell growth in addition to improving the detoxification and antioxidant capacity of cells, which is particularly important for cancer prevention.The mechanism of cell inhibition and cytotoxicity of sulforaphane includes induction of cell apoptosis, inhibition of cell cycle progression and inhibition of angiogenesis, targeting multiple sites of key cell signaling pathways of tumor cells, and playing an anti-tumor effect similar to that of targeted drugs.This review introduces the possible mechanism of sulforaphane in clinical adjuvant chemotherapy and radiotherapy for breast cancer, ovarian and cervical cancer, and provides theoretical clues for its clinical application in breast cancer and ovarian and cervical cancer.

导出引用

张维，李苏宜. 萝卜硫素在乳腺癌、卵巢癌及宫颈癌中的潜在作用[J]. 肿瘤代谢与营养电子杂志. 2020, 7(4): 391-395 https://doi.org/10.16689/j.cnki.cn11-9349/r.2020.04.003

Zhang Wei, Li Suyi. The potential role of sulforaphane in breast cancer, ovarian cancer and cervical cancer[J]. Electronic Journal of Metabolism and Nutrition of Cancer. 2020, 7(4): 391-395 https://doi.org/10.16689/j.cnki.cn11-9349/r.2020.04.003

参考文献

1.BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］. CA Cancer J Clin, 2018, 68(6): 394-424.
2.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］. Int J Epidemiol, 2017, 46(3): 1029-1056.
3.TURATI F, ROSSI M, PELUCCHI C, et al. Fruit and vegetables and cancer risk: a review of southern European studies［J］. Br J Nutr, 2015, 113 Suppl 2: S102-S110.
4.VIEIRA A R, ABAR L, VINGELIENE S, et al. Fruits, vegetables and lung cancer risk: a systematic review and meta-analysis［J］. Ann Oncol, 2016, 27(1): 81-96.
5.KIM C, KIM B. Anti-cancer natural products and their bioactive compounds inducing ER stress-mediated apoptosis: a review［J］. Nutrients, 2018, 10(8).
6.NICASTRO H L, ROSS S A, MILNER J A. Garlic and onions: their cancer prevention properties［J］. Cancer Prev Res (Phila), 2015, 8(3): 181-189.
7.ZIELONKA J, JOSEPH J, SIKORA A, et al. Mitochondria-targeted triphenylphosphonium-based compounds: syntheses, mechanisms of action, and therapeutic and diagnostic applications［J］. Chem Rev, 2017, 117(15): 10043-10120.
8.PAUL S, GENG C A, YANG T H, et al. Phytochemical and health-beneficial progress of gurnip (brassica rapa)［J］. J Food Sci, 2019, 84(1): 19-30.
9.MOCNIAK L E, ELKIN K, BOLLINGER J J. Lifetimes of the aglycone substrates of specifier proteins, the autonomous iron enzymes that dictate the products of the glucosinolate-myrosinase defense system in brassica plants［J］. Biochemistry, 2020,59(26):2432-2441.
10.ABBAOUI B, LUCAS C R, RIEDL K M, et al. Cruciferous vegetables, isothiocyanates, and bladder cancer prevention［J］. Mol Nutr Food Res, 2018, 62(18): e1800079.
11.LI Y, LI S, MENG X, et al. Dietary natural products for prevention and treatment of breast cancer［J］. Nutrients, 2017, 9（7）：728.
12.FUJIOKA N, FRITZ V, UPADHYAYA P, et al. Research on cruciferous vegetables, indole-3-carbinol, and cancer prevention: A tribute to Lee W. Wattenberg［J］. Mol Nutr Food Res, 2016, 60(6): 1228-1238.
13.KAPUSTA-DUCH J, KOPEC′ A, PIATKOWSKA E, et al. The beneficial effects of Brassica vegetables on human health［J］. Rocz Panstw Zakl Hig, 2012, 63(4): 389-395.
14.VANDUCHOVA A, ANZENBACHER P, ANZENBACHEROVA E. Isothiocyanate from broccoli, sulforaphane, and its properties［J］. J Med Food, 2019, 22(2): 121-126.
15.KIM C, KIM B. Anti-cancer natural products and their bioactive compounds inducing ER stress-mediated apoptosis: a review［J］. Nutrients, 2018, 10(8):1021.
16.HUNAKOVA L, HORVATHOVA E, MAJEROVA K, et al. Genotoxic effects of tributyltin and triphenyltin isothiocyanates, cognate RXR ligands: comparison in human breast carcinoma MCF 7 and MDA-MB-231 cells［J］. Int J Mol Sci, 2019, 20(5).
17.VANDUCHOVA A, ANZENBACHER P, ANZENBACHEROVA E. Isothiocyanate from broccoli, sulforaphane, and its properties［J］. J Med Food, 2019, 22(2): 121-126.
18.GASPER A V, AL-JANOBI A, SMITH J A, et al. Glutathione S-transferase M1 polymorphism and metabolism of sulforaphane from standard and high-glucosinolate broccoli［J］. Am J Clin Nutr, 2005, 82(6): 1283-1291.
19.YAGISHITA Y, FAHEY J W, DINKOVA-KOSTOVA A T, et al. Broccoli or sulforaphane: is it the source or dose that matters?［J］. Molecules, 2019, 24(19).
20.YANG L, PALLIYAGURU D L, KENSLER T W. Frugal chemoprevention: targeting Nrf2 with foods rich in sulforaphane［J］. Semin Oncol, 2016, 43(1): 146-153.
21.JIANG X, LIU Y, MA L, et al. Chemopreventive activity of sulforaphane［J］. Drug Des Devel Ther, 2018, 12: 2905-2913.
22.LIU P, WANG W, ZHOU Z, et al. Chemopreventive activities of sulforaphane and its metabolites in human hepatoma HepG2 cells［J］. Nutrients, 2018, 10(5):123-128.
23.BAYAT M R, BALUCH N, HOMAYOUNI T S, et al. The role of Sulforaphane in cancer chemoprevention and health benefits: a mini-review［J］. J Cell Commun Signal, 2018, 12(1): 91-101.
24.ZHU H, JIA Z, STROBL J S, et al. Potent induction of total cellular and mitochondrial antioxidants and phase 2 enzymes by cruciferous sulforaphane in rat aortic smooth muscle cells: cytoprotection against oxidative and electrophilic stress［J］. Cardiovasc Toxicol, 2008, 8(3): 115-125.
25.WAN H W, KWAK M K, MAKPOL S, et al. Piper betle induces phase I & II genes through Nrf2/ARE signaling pathway in mouse embryonic fibroblasts derived from wild type and Nrf2knockout cells［J］. BMC Complement Altern Med, 2014, 14: 72.
26.MYZAK M C, DASHWOOD R H. Chemoprotection by sulforaphane: keep one eye beyond Keap1［J］. Cancer Lett, 2006, 233(2): 208-218.
27.RAI R, GONG E K, MANGIARACINA B D, et al. Preclinical efficacy and involvement of AKT, mTOR, and ERK kinases in the mechanism of sulforaphane against endometrial cancer［J］. Cancers (Basel), 2020, 12(5):357-363.
28.JAKUBKOV J, SEDLK J, MITHEN R, et al. Role of PI3K/Akt and MEK/ERK signaling pathways in sulforaphane- and erucin-induced phase II enzymes and MRP2 transcription, G2/M arrest and cell death in Caco-2 cells［J］. Biochem Pharmacol, 2005, 69(11): 1543-1552.
29.TORTORELLA S M, ROYCE S G, LICCIARDI P V, et al. Dietary sulforaphane in cancer chemoprevention: the role of epigenetic regulation and HDAC inhibition［J］. Antioxid Redox Signal, 2015, 22(16): 1382-1424.
30.HOSSAIN S, LIU Z, WOOD R J. Histone deacetylase activity and vitamin D-dependent gene expressions in relation to sulforaphane in human breast cancer cells［J］. J Food Biochem, 2020, 44(2): e13114.
31.AUMEERUDDY M Z, MAHOMOODALLY M F. Combating breast cancer using combination therapy with 3 phytochemicals: Piperine, sulforaphane, and thymoquinone［J］. Cancer, 2019, 125(10): 1600-1611.
32.ROYSTON K J, PAUL B, NOZELL S, et al. Withaferin A and sulforaphane regulate breast cancer cell cycle progression through epigenetic mechanisms［J］. Exp Cell Res, 2018, 368(1): 67-74.
33.DANDAWATE P R, SUBRAMANIAM D, JENSEN R A, et al. Targeting cancer stem cells and signaling pathways by phytochemicals: novel approach for breast cancer therapy［J］. Semin Cancer Biol, 2016, 40-41: 192-208.
34.SHUKLA S, PENTA D, MONDAL P, et al. Epigenetics of breast cancer: clinical status of Epi-drugs and phytochemicals［J］. Adv Exp Med Biol, 2019, 1152: 293-310.
35.CORNBLATT B S, YE L, DINKOVA-KOSTOVA A T, et al. Preclinical and clinical evaluation of sulforaphane for chemoprevention in the breast［J］. Carcinogenesis, 2007, 28(7): 1485-1490.
36.PAWLIK A, SOMIN′SKA-WOJEWDZKA M, HERMAN-ANTOSIEWICZ A. Sensitization of estrogen receptor-positive breast cancer cell lines to 4-hydroxytamoxifen by isothiocyanates present in cruciferous plants［J］. Eur J Nutr, 2016, 55(3): 1165-1180.
37.PAWLIK A, WICZK A, KACZYC′SKA A, et al. Sulforaphane inhibits growth of phenotypically different breast cancer cells［J］. Eur J Nutr, 2013, 52(8): 1949-1958.
38.LUBECKA-PIETRUSZEWSKA K, KAUFMAN-SZYMCZYK A, STEFANSKA B, et al. Sulforaphane alone and in combination with clofarabine epigenetically regulates the expression of DNA methylation-silenced tumour suppressor genes in human breast cancer cells［J］. J Nutrigenet Nutrigenomics, 2015, 8(2): 91-101.
39.HUSSAIN A, MOHSIN J, PRABHU S A, et al. Sulforaphane inhibits growth of human breast cancer cells and augments the therapeutic index of the chemotherapeutic drug, gemcitabine［J］. Asian Pac J Cancer Prev, 2013, 14(10): 5855-5860.
40.KHEIRI M H, SHARAFI A, ATTARI E, et al. Pharmacokinetics and in vitro and in vivo delivery of sulforaphane by PCL-PEG-PCL copolymeric-based micelles［J］. Artif Cells Nanomed Biotechnol, 2017, 45(8): 1728-1739.
41.TIAN M, TIAN D, QIAO X, et al. Modulation of Myb-induced NF-κB -STAT3 signaling and resulting cisplatin resistance in ovarian cancer by dietary factors［J］. J Cell Physiol, 2019, 234(11): 21126-21134.
42.PISTOLLATO F, CALDERN I R, RUIZ R, et al. The use of natural compounds for the targeting and chemoprevention of ovarian cancer［J］. Cancer Lett, 2017, 411: 191-200.
43.BRYANT C S, KUMAR S, CHAMALA S, et al. Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells［J］. Mol Cancer, 2010, 9: 47.
44.LI S, WEI Y. Association of HMGB1, BRCA1 and P62 expression in ovarian cancer and chemotherapy sensitivity［J］. Oncol Lett, 2018, 15(6): 9572-9576.
45.LI S, ZHAO X, CHANG S, et al. ERp57-small interfering RNA silencing can enhance the sensitivity of drug-resistant human ovarian cancer cells to paclitaxel［J］. Int J Oncol, 2019, 54(1): 249-260.
46.SANTANA-GLVEZ J, VILLELA-CASTREJN J, SERNA-SALDVAR S O, et al. Synergistic combinations of curcumin, sulforaphane, and dihydrocaffeic acid against human colon cancer cells［J］. Int J Mol Sci, 2020, 21(9):325-331.
47.SU X, JIANG X, MENG L, et al. Anticancer activity of sulforaphane: the epigenetic mechanisms and the Nrf2 signaling pathway［J］. Oxid Med Cell Longev, 2018, 2018: 5438179.
48.CHENG Y M, TSAI C C, HSU Y C. Sulforaphane, a Dietary isothiocyanate, induces G2/M arrest in cervical cancer cells through CyclinB1 downregulation and GADD45β/CDC2 association［J］. Int J Mol Sci, 2016, 17(9):1463-1472.
49.SHARMA C, SADRIEH L, PRIYANI A, et al. Anti-carcinogenic effects of sulforaphane in association with its apoptosis-inducing and anti-inflammatory properties in human cervical cancer cells［J］. Cancer Epidemiol, 2011, 35(3): 272-278.
50.CHOI Y J, LEE W S, LEE E G, et al. Sulforaphane inhibits IL-1β-induced proliferation of rheumatoid arthritis synovial fibroblasts and the production of MMPs, COX-2, and PGE2［J］. Inflammation, 2014, 37(5): 1496-1503.
51.KHEIRI M H, SHARAFI A, ATTARI E, et al. Pharmacokinetics and in vitro and in vivo delivery of sulforaphane by PCL-PEG-PCL copolymeric-based micelles［J］. Artif Cells Nanomed Biotechnol, 2017, 45(8): 1728-1739.
52.QIN W S, DENG Y H, CUI F C. Sulforaphane protects against acrolein-induced oxidative stress and inflammatory responses: modulation of Nrf-2 and COX-2 expression［J］. Arch Med Sci, 2016, 12(4): 871-880.
53.KOTOWSKI U, HEIDUSCHKA G, BRUNNER M, et al. Radiosensitization of head and neck cancer cells by the phytochemical agent sulforaphane［J］. Strahlenther Onkol, 2011, 187(9): 575-580.
54.YU D, SEKINE-SUZUKI E, XUE L, et al. Chemopreventive agent sulforaphane enhances radiosensitivity in human tumor cells［J］. Int J Cancer, 2009, 125(5): 1205-1211.
55.KNTAYYA S B, IBRAHIM M D, MOHD A N, et al. Induction of apoptosis and cytotoxicity by isothiocyanate sulforaphene in human hepatocarcinoma HepG2 cells［J］. Nutrients, 2018, 10(6):742-753.
56.LAN F, PAN Q, YU H, et al. Sulforaphane enhances temozolomide-induced apoptosis because of down-regulation of miR-21 via Wnt/β-catenin signaling in glioblastoma［J］. J Neurochem, 2015, 134(5): 811-818.
57.ROYSTON K J, TOLLEFSBOL T O. The epigenetic impact of cruciferous vegetables on cancer prevention［J］. Curr Pharmacol Rep, 2015, 1(1): 46-51.
58.PAWLIK A, WAA M, HAC′ A, et al. Sulforaphene, an isothiocyanate present in radish plants, inhibits proliferation of human breast cancer cells［J］. Phytomedicine, 2017, 29: 1-10.
59.ZENG H, TRUJILLO O N, MOYER M P, et al. Prolonged sulforaphane treatment activates survival signaling in nontumorigenic NCM460 colon cells but apoptotic signaling in tumorigenic HCT116 colon cells［J］. Nutr Cancer, 2011, 63(2): 248-255.