Research progress on the mechanism of sulforaphane in the treatment of digestive system tumors

doi:10.3760/cma.j.issn.1007-1245.2023.19.016

Abstract

Abstract:

The mortality rate of digestive system cancer is among the highest in the world. Traditional treatment methods, including surgery, chemotherapy, and radiotherapy, have the disadvantages of poor efficacy and drug resistance. In recent years, sulforaphane, as a natural anti-tumor compound, has been widely studied in digestive system tumors. It can treat cancer by promoting cancer cell death, hindering cancer cell proliferation, inhibiting cancer cell invasion and metastasis, anti-angiogenesis, strengthening immunotherapy, and weakening drug resistance. This article reviews the research progress of sulforaphane in the treatment of digestive system tumors in domestic and foreign research institutions, so as to provide new ideas for the treatment of digestive system tumors.

Key words:

Sulforaphane, Digestive system tumors, Mechanisms of treatment, Progress

摘要：

消化系统肿瘤病死率在全球肿瘤中位于前列，包括手术、化疗和放疗在内的传统治疗方法存在效果差和耐药的缺点。近年来，萝卜硫素作为一种天然抗肿瘤化合物在消化系统肿瘤中被广泛研究，可通过促进癌细胞死亡、阻碍癌细胞增殖、抑制癌细胞侵袭和转移、抗血管生成、加强免疫治疗及减弱耐药性等机制来治疗癌症。本文综述了国内外研究机构关于萝卜硫素治疗消化系统肿瘤机制的研究进展，为消化系统肿瘤的治疗提供新思路。

关键词:

萝卜硫素, 消化系统肿瘤, 治疗机制, 进展

An Jiaqi, Xie Qingzhi.

Research progress on the mechanism of sulforaphane in the treatment of digestive system tumors [J]. International Medicine and Health Guidance News, 2023, 29(19): 2732-2736.

安嘉琪谢庆芝.

萝卜硫素在消化系统肿瘤治疗中的机制研究进展 [J]. 国际医药卫生导报, 2023, 29(19): 2732-2736.

References

[1] Hanahan D.Hallmarks of cancer: new dimensions[J].Cancer Discov,2022,12(1):31-46.DOI:10.1158/2159-8290.CD-21-1059.
[2] Arnold M, Abnet CC, Neale RE, et al. Global burden of 5 major types of gastrointestinal cancer[J].Gastroenterology,2020,159(1):335-349.e15.DOI:10.1053/j.gastro.2020.02.068.
[3] 周家琛,郑荣寿,王少明,等. 2020年中国和世界部分国家主要消化道肿瘤负担比较[J/CD]. 肿瘤综合治疗电子杂志,2021,7(2):26-32.DOI:10.12151/JMCM.2021.02-04.
[4] Kaiser AE, Baniasadi M, Giansiracusa D, et al. Sulforaphane: a broccoli bioactive phytocompound with cancer preventive potential[J].Cancers (Basel),2021,13(19):4796.DOI:10.3390/cancers13194796.
[5] Martin SL, Kala R, Tollefsbol TO. Mechanisms for the inhibition of colon cancer cells by sulforaphane through epigenetic modulation of microRNA-21 and human telomerase reverse transcriptase (hTERT) down-regulation[J].Curr Cancer Drug Targets,2018,18(1):97-106.DOI:10.2174/1568009617666170206104032.
[6] Peng ZT, Gu P. Sulforaphane suppresses autophagy during the malignant progression of gastric carcinoma via activating miR-4521/PIK3R3 pathway[J].Hum Exp Toxicol,2021,40(12_suppl):S711-S720.DOI:10.1177/09603271211054437.
[7] Kiani S, Akhavan-Niaki H, Fattahi S, et al. Purified sulforaphane from broccoli (Brassica oleracea var. italica) leads to alterations of CDX1 and CDX2 expression and changes in miR-9 and miR-326 levels in human gastric cancer cells[J].Gene,2018,678:115-123.DOI:10.1016/j.gene.2018.08.026.
[8] Han S, Wang Z, Liu J, et al. miR-29a-3p-dependent COL3A1 and COL5A1 expression reduction assists sulforaphane to inhibit gastric cancer progression[J].Biochem Pharmacol,2021,188:114539.DOI:10.1016/j.bcp.2021.114539.
[9] Yin L, Xiao X, Georgikou C, et al. MicroRNA-365a-3p inhibits c-Rel-mediated NF-κB signaling and the progression of pancreatic cancer[J].Cancer Lett,2019,452:203-212.DOI:10.1016/j.canlet.2019.03.025.
[10] Wang Y, Petrikova E, Gross W, et al. Sulforaphane promotes dendritic cell stimulatory capacity through modulation of regulatory molecules, JAK/STAT3- and microRNA-signaling[J].Front Immunol,2020,11:589818.DOI:10.3389/fimmu.2020.589818.
[11] Yin L, Xiao X, Georgikou C, et al. Sulforaphane induces miR135b-5p and its target gene, RASAL2, thereby inhibiting the progression of pancreatic cancer[J].Mol Ther Oncolytics,2019,14:74-81.DOI:10.1016/j.omto.2019.03.011.
[12] Georgikou C, Yin L, Gladkich J, et al. Inhibition of miR30a-3p by sulforaphane enhances gap junction intercellular communication in pancreatic cancer[J].Cancer Lett,2020,469:238-245.DOI:10.1016/j.canlet.2019.10.042.
[13] Fang JY, Richardson BC. The MAPK signalling pathways and colorectal cancer[J].Lancet Oncol,2005,6(5):322-327.DOI:10.1016/S1470-2045(05)70168-6.
[14] Dos Santos PWDS, Machado ART, De Grandis RA, et al. Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells[J].Food Chem Toxicol,2020,136:111047.DOI:10.1016/j.fct.2019.111047.
[15] Hao Q, Wang M, Sun NX, et al. Sulforaphane suppresses carcinogenesis of colorectal cancer through the ERK/Nrf2‑UDP glucuronosyltransferase 1A metabolic axis activation[J].Oncol Rep,2020,43(4):1067-1080.DOI:10.3892/or.2020.7495.
[16] Shen G, Xu C, Chen C, et al. p53-independent G1 cell cycle arrest of human colon carcinoma cells HT-29 by sulforaphane is associated with induction of p21CIP1 and inhibition of expression of cyclin D1[J].Cancer Chemother Pharmacol,2006,57(3):317-327.DOI:10.1007/s00280-005-0050-3.
[17] Li S, Khoi PN, Yin H, et al. Sulforaphane suppresses the nicotine-induced expression of the matrix metalloproteinase-9 via inhibiting ROS-mediated AP-1 and NF-κB signaling in human gastric cancer cells[J].Int J Mol Sci,2022,23(9):5172.DOI:10.3390/ijms23095172.
[18] Parnaud G, Li P, Cassar G, et al. Mechanism of sulforaphane-induced cell cycle arrest and apoptosis in human colon cancer cells[J].Nutr Cancer,2004,48(2):198-206.DOI:10.1207/s15327914nc4802_10.
[19] Wang Y, Wu H, Dong N, et al. Sulforaphane induces S-phase arrest and apoptosis via p53-dependent manner in gastric cancer cells[J].Sci Rep,2021,11(1):2504.DOI:10.1038/s41598-021-81815-2.
[20] Chen Y, Wang MH, Zhu JY, et al. TAp63α targeting of Lgr5 mediates colorectal cancer stem cell properties and sulforaphane inhibition[J].Oncogenesis,2020,9(10):89.DOI:10.1038/s41389-020-00273-z.
[21] Park SY, Kim GY, Bae SJ, et al. Induction of apoptosis by isothiocyanate sulforaphane in human cervical carcinoma HeLa and hepatocarcinoma HepG2 cells through activation of caspase-3[J].Oncol Rep,2007,18(1):181-187.
[22] Liu KC, Shih TY, Kuo CL, et al. Sulforaphane induces cell death through G2/M phase arrest and triggers apoptosis in HCT 116 human colon cancer cells[J].Am J Chin Med,2016,44(6):1289-1310.DOI:10.1142/S0192415X16500725.
[23] Lu Z, Ren Y, Yang L, et al. Inhibiting autophagy enhances sulforaphane-induced apoptosis via targeting NRF2 in esophageal squamous cell carcinoma[J].Acta Pharm Sin B,2021,11(5):1246-1260.DOI:10.1016/j.apsb.2020.12.009.
[24] Lu Z, Zhang Y, Xu Y, et al. mTOR inhibitor PP242 increases antitumor activity of sulforaphane by blocking Akt/mTOR pathway in esophageal squamous cell carcinoma[J].Mol Biol Rep,2022,49(1):451-461.DOI:10.1007/s11033-021-06895-9.
[25] Takebe N, Miele L, Harris PJ, et al. Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update[J].Nat Rev Clin Oncol,2015,12(8):445-464.DOI:10.1038/nrclinonc.2015.61.
[26] Li SH, Fu J, Watkins DN, et al. Sulforaphane regulates self-renewal of pancreatic cancer stem cells through the modulation of Sonic hedgehog-GLI pathway[J].Mol Cell Biochem,2013,373(1-2):217-227.DOI:10.1007/s11010-012-1493-6.
[27] Ge M, Zhang L, Cao L, et al. Sulforaphane inhibits gastric cancer stem cells via suppressing sonic hedgehog pathway[J].Int J Food Sci Nutr,2019,70(5):570-578.DOI:10.1080/09637486.2018.1545012.
[28] Li Y, Karagöz GE, Seo YH, et al. Sulforaphane inhibits pancreatic cancer through disrupting Hsp90-p50(Cdc37) complex and direct interactions with amino acids residues of Hsp90[J].J Nutr Biochem,2012,23(12):1617-1626.DOI:10.1016/j.jnutbio.2011.11.004.
[29] Zheng K, Ma J, Wang Y, et al. Sulforaphane inhibits autophagy and induces exosome-mediated paracrine senescence via regulating mTOR/TFE3[J].Mol Nutr Food Res,2020,64(14):e1901231.DOI:10.1002/mnfr.201901231.
[30] Choi YH. ROS-mediated activation of AMPK plays a critical role in sulforaphane-induced apoptosis and mitotic arrest in AGS human gastric cancer cells[J].Gen Physiol Biophys,2018,37(2):129-140.DOI:10.4149/gpb_2017026.
[31] Dong QQ, Wang QT, Wang L, et al. SMYD3-associated pathway is involved in the anti-tumor effects of sulforaphane on gastric carcinoma cells[J].Food Sci Biotechnol,2018,27(4):1165-1173.DOI:10.1007/s10068-018-0337-x.
[32] Wu J, Han J, Hou B, et al. Sulforaphane inhibits TGF-β-induced epithelial-mesenchymal transition of hepatocellular carcinoma cells via the reactive oxygen species-dependent pathway[J].Oncol Rep,2016,35(5):2977-2983.DOI:10.3892/or.2016.4638.
[33] Luo Y, Yan B, Liu L, et al. Sulforaphane inhibits the expression of long noncoding RNA H19 and its target APOBEC3G and thereby pancreatic cancer progression[J].Cancers (Basel),2021,13(4):827.DOI:10.3390/cancers13040827.
[34] Liu P, Atkinson SJ, Akbareian SE, et al. Sulforaphane exerts anti-angiogenesis effects against hepatocellular carcinoma through inhibition of STAT3/HIF-1α/VEGF signalling[J].Sci Rep,2017,7(1):12651.DOI:10.1038/s41598-017-12855-w.