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水仙环素的抗肿瘤活性及机制研究进展

杨敏 林琪琪 刘丹丹 周宏宇

杨敏, 林琪琪, 刘丹丹, 周宏宇. 水仙环素的抗肿瘤活性及机制研究进展[J]. 昆明医科大学学报, 2024, 45(2): 153-159. doi: 10.12259/j.issn.2095-610X.S20240222
引用本文: 杨敏, 林琪琪, 刘丹丹, 周宏宇. 水仙环素的抗肿瘤活性及机制研究进展[J]. 昆明医科大学学报, 2024, 45(2): 153-159. doi: 10.12259/j.issn.2095-610X.S20240222
Min YANG, Qiqi LIN, Dandan LIU, Hongyu ZHOU. Research Progress on the Anti-tumor Activity and Mechanism of Narciclasine[J]. Journal of Kunming Medical University, 2024, 45(2): 153-159. doi: 10.12259/j.issn.2095-610X.S20240222
Citation: Min YANG, Qiqi LIN, Dandan LIU, Hongyu ZHOU. Research Progress on the Anti-tumor Activity and Mechanism of Narciclasine[J]. Journal of Kunming Medical University, 2024, 45(2): 153-159. doi: 10.12259/j.issn.2095-610X.S20240222

水仙环素的抗肿瘤活性及机制研究进展

doi: 10.12259/j.issn.2095-610X.S20240222
基金项目: 国家自然科学基金资助项目(21907044,82160697);云南省基础研究计划面上项目(202101AT070155);云南省科技厅-昆明医科大学联合专项基金资助项目( 202101AY070001-011); 云南省“兴滇英才支持计划”青年人才项目(YNWR-QNBJ-2018-380,YNWR-QNBJ-2020-276)
详细信息
    作者简介:

    杨敏(2001~),女,重庆大足人,在读2020级药学专业本科生

    通讯作者:

    刘丹丹,E-mail:liudandan@kmmu.edu.cn

    周宏宇,E-mail:zhouhongyu@kmmu.edu.cn

  • 中图分类号: R966

Research Progress on the Anti-tumor Activity and Mechanism of Narciclasine

  • 摘要: 水仙环素(narciclasine,NCS)是从石蒜科水仙属植物水仙的鳞茎中提取出的水鬼蕉碱型生物碱,被证实对多种肿瘤细胞具有显著的抑制活性。NCS的抗肿瘤作用机制多样,通过不同途径产生抗肿瘤作用,适应了当前研发多靶点抗肿瘤药物的趋向。本文结合NCS抑制乳腺癌细胞、结肠癌细胞、胃癌细胞、黑色素瘤细胞、多形性胶质母细胞瘤细胞、口腔癌细胞和原发性渗出性淋巴瘤细胞的作用及分子机制,对NCS近年来的抗肿瘤活性及作用机制研究进行综述,旨在为将来NCS类抗肿瘤药物的研发与设计提供思路和借鉴。
  • 图  1  水仙环素的化学结构[4]

    Figure  1.  Chemical structure of NCS

  • [1] 毕凯健. 水仙环素衍生物的设计、合成及抗肿瘤活性研究[D]. 上海: 第二军医大学, 2016.
    [2] Antoszczak M. A medicinal chemistry perspective on sali-nomycin as a potent anticancer and anti-CSCs agent[J]. Eur J Med Chem,2019,164:366-377. doi: 10.1016/j.ejmech.2018.12.057
    [3] Dagogo-Jack I,Shaw A T. Tumour heterogeneity and re-sistance to cancer therapies[J]. Nat Rev Clin Oncol,2018,15(2):81-94. doi: 10.1038/nrclinonc.2017.166
    [4] Ingrassia L,Lefranc F,Dewelle J,et al. Structure-activity relationship analysis of novel derivatives of narciclasine (an Amaryllidaceae isocarbostyril derivative) as potential anticancer agents[J]. J Med Chem,2009,52(4):1100-1114. doi: 10.1021/jm8013585
    [5] Ceriotti G. Narciclasine: An antimitotic substance from Narcissus bulbs[J]. Nature,1967,21(5076):595-596.
    [6] Fürst R. Narciclasine - an amaryllidaceae alkaloid with potent antitumor and anti-inflammatory properties[J]. Planta Med,2016,82(16):1389-1394. doi: 10.1055/s-0042-115034
    [7] Rárová L,Ncube B,Van Staden J,et al. Identification of Narciclasine as an in vitro anti-inflammatory component of Cyrtanthus contractus by correlation-based metabolomics[J]. Nat Prod,2019,82(5):1372-1376. doi: 10.1021/acs.jnatprod.8b00973
    [8] Bräutigam J,Bischoff I,Schürmann C,et al. Narciclasine inhibits angiogenic processes by activation of rho kinase and by downregulation of the VEGF receptor 2[J]. Mol Cell Cardiol,2019,135:97-108. doi: 10.1016/j.yjmcc.2019.08.001
    [9] De Castro Barbosa E,Alves T M A,Kohlhoff M,et al. Searching for plant-derived antivirals against dengue virus and Zika virus[J]. Virol J,2022,19(1):31.
    [10] Dumont P,Ingrassia L,Rouzeau S,et al. The Amaryllidaceae isocarbostyril narciclasine induces apoptosis by activation of the death receptor and/or mitochondrial pathways in cancer cells but not in normal fibroblasts[J]. Neoplasia,2007,9(9):766-776. doi: 10.1593/neo.07535
    [11] Min B S,Cao J J,Nakamura N,et al. Cytotoxic alkaloids and a Fla Villi from the bulbs of Crinum asiaticum var japonicum[J]. Chem Plmrm Bull,2001,49(9):1217-1219. doi: 10.1248/cpb.49.1217
    [12] Van Goietsenoven G,Mathieu V,Lefranc F,et al. Narciclasine as well as other Amaryllidaceae isocarbostyrils are promising GTP-ase targeting agents against brain cancers[J]. Med Res Rev,2013,33(2):439-455.
    [13] Qiu Y,Fang B,Thuy N T T,et al. Narciclasine suppresses esophageal cancer cell proliferation and migration by inhibiting the FAK signaling pathway[J]. Eur J Pharmacol,2022,921:174669.
    [14] 马楠楠,陈宁,季宇彬,等. 水鬼蕉生物碱抗肿瘤研究进展[J]. 黑龙江医药,2013,26(2):205-208. doi: 10.3969/j.issn.1006-2882.2013.02.017
    [15] Kornienko A,Evidente A. Chemistry,biology,and medicinal potential of NCS and its congeners[J]. Chem Rev,2008,108(6):1982-2014. doi: 10.1021/cr078198u
    [16] Cao C,Huang W,Zhang N,et al. NCS induces autophagy-dependent apoptosis in triple-negative breast cancer cells by regulating the AMPK-ULK1 axis[J]. Cell Prolif,2018,51(6):12518. doi: 10.1111/cpr.12518
    [17] Beebe J D,Li J Y,Zhang J T. Two decades of research in discovery of anticancer drugs targeting STAT3,how close are we?[J]. Pharmacol Ther,2018,191:74-91. doi: 10.1016/j.pharmthera.2018.06.006
    [18] Mohan C D,Rangappa S,Preetham H D,et al. Targeting STAT3 signaling pathway in cancer by agents derived from Mother Nature[J]. Cancer Biol,2022,80:157-182. doi: 10.1016/j.semcancer.2020.03.016
    [19] Lv C,Huang Y,Huang R,et al. Narciclasine targets STAT3 via distinct mechanisms in tamoxifen-resistant breast cancer cells[J]. Mol Ther Oncolytics,2022,24:340-354. doi: 10.1016/j.omto.2021.12.025
    [20] Wang M,Liang L,Wang R,et al. Narciclasine,a novel topoisomerase I inhibitor,exhibited potent anti-cancer activity against cancer cells[J]. Nat Prod Bioprospect,2023,13(1):27. doi: 10.1007/s13659-023-00392-1
    [21] Liu L F,Wang J C. Supercoiling of the DNA template during transcription[J]. Proc Natl AcadSci USA,1987,84(20):7024-7027. doi: 10.1073/pnas.84.20.7024
    [22] Lichota A,Gwozdzinski K. Anticancer Activity of Natural Compounds from Plant and Marine Environment[J]. Int J Mol Sci,2018,19(11):3533. doi: 10.3390/ijms19113533
    [23] Pommiier Y,Pourquier P,Urasaki Y,et al. Topoisomerase 1 inhibitors: selectivity andcellular resistance[J]. Drug Resist Updat,1999,2(5):307-318. doi: 10.1054/drup.1999.0102
    [24] Said A H,Raufman J P,Xie G. The role of matrix metalloproteinases in colorectal cancer[J]. Cancers,2014,6:366-375. doi: 10.3390/cancers6010366
    [25] Pezeshkian Z,Nobili S,Peyravian N,et al. Insights into the Role of Matrix Metalloproteinases in Precancerous Conditions and in Colorectal Cancer[J]. Cancers,2021,13(24):6226. doi: 10.3390/cancers13246226
    [26] Ara ú jo R F,Jr,Lira G A,et al. Prognostic and diagnostic implications of MMP-2,MMP-9,and VEGF-α expressions in colorectal cancer[J]. Pathol Res Pract,2015,211(1):71-77. doi: 10.1016/j.prp.2014.09.007
    [27] Wang K,Zheng J,Yu J,et al. Knockdown of MMP-1 inhibits the progression of colorectal cancer by suppressing the PI3K/Akt/c-myc signaling pathway and EMT[J]. Oncol Rep,2020,43(4):1103-1112.
    [28] Mathieu V,Laguera B,Masi M,et al. Amaryllidaceae alkaloids decrease the proliferation,invasion,and secretion of clinically relevant cytokines by cultured human colon cancer cells[J]. Biomolecules,2022,12(9):1267. doi: 10.3390/biom12091267
    [29] Bie Y, Ge W, Yang Z, et al. The crucial role of CXCL8 and its receptors in colorectal liver metastasis[J]. Dis Markers, 2019, 2019: 8023460.
    [30] Wang Y,Wang K,Han GC,et al. Neutrophil infiltration favors colitis-associated tumorigenesis by activating the interleukin-1 (IL-1)/IL-6 axis[J]. Mucosal Immunol,2014,7(5):1106-1115. doi: 10.1038/mi.2013.126
    [31] Lin Y,He Z,Ye J,et al. Progress in Understanding the IL-6/STAT3 Pathway in Colorectal Cancer[J]. Onco Targets Ther,2020,13:13023-13032. doi: 10.2147/OTT.S278013
    [32] Yuan Y,He X,Li X,et al. NCS induces autophagy-mediated apoptosis in gastric cancer cells through the Akt/mTOR signaling pathway[J]. BMC Pharmacol Toxicol,2021,22(1):70. doi: 10.1186/s40360-021-00537-3
    [33] White E,Mehnert J M,Chan C S. Autophagy,metabolism,and Cancer[J]. Clin Cancer Res,2015,21:5037-5046. doi: 10.1158/1078-0432.CCR-15-0490
    [34] Deng S,Shanmugam M K,Kumar A P,et al. Targeting autophagy using natural compounds for cancer prevention and therapy[J]. Cancer,2019,125(8):1228-1246. doi: 10.1002/cncr.31978
    [35] Marino G, Niso-Santano M, Baehrecke E H, et al Self-consumption: the interplay of autophagy and apoptosis[J]. Nat Rev Mol Cell Biol, 2014, 15(2): 81–94.
    [36] Moosavi M A,Haghi A,Rahmati M,et al. Phytochemicals as potent modulators of autophagy for cancer therapy[J]. Cancer Lett,2018,424:46-69. doi: 10.1016/j.canlet.2018.02.030
    [37] Liu R,Li J,Zhang T,et al. Itraconazole suppresses the growth of glioblastoma through induction of autophagy: involvement of abnormal cholesterol trafficking[J]. Autophagy,2014,10(7):1241-1255. doi: 10.4161/auto.28912
    [38] Elgendy M,Sheridan C,Brumatti G,et al. Oncogenic ras-induced expression of Noxa and Beclin-1 promotes autophagic cell death and limits clonogenic survival[J]. Mol Cell,2011,42(1):23-35. doi: 10.1016/j.molcel.2011.02.009
    [39] He C,Klionsky D J. Regulation mechanisms and signaling pathways of autophagy[J]. Annu Rev Genet,2009,43:67-93. doi: 10.1146/annurev-genet-102808-114910
    [40] Jung C H,Ro S H,Cao J,et al. mTOR regulation of autophagy[J]. FEBS Lett,2010,584(7):1287-1295. doi: 10.1016/j.febslet.2010.01.017
    [41] Van Goietsenoven G,Hutton J,Becker J P,et al. Targeting of eEF1A with Amaryllidaceae isocarbostyrils as a strategy to combat melanomas[J]. FASEB J,2010,24(11):4575-4584. doi: 10.1096/fj.10-162263
    [42] Lefranc F,Sauvage S,Van Goietsenoven G,et al. NCS,a plant growth modulator,activates Rho and stress fibers in glioblastoma cells[J]. Mol Cancer Ther,2009,8(7):1739-1750. doi: 10.1158/1535-7163.MCT-08-0932
    [43] Scott R W,Olson M. LIM kinases: function,regulation and association with human disease[J]. J Mol Med,2007,85(6):555-568. doi: 10.1007/s00109-007-0165-6
    [44] Arber S,Barbayannis F A,Hanser H,et al. Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase[J]. Nature,1998,393(6687):805-809. doi: 10.1038/31729
    [45] Le Mercier M,Mathieu V,Haibe-Kains B,et al. Knocking down galectin-1 in human Hs683 glioblastoma cells impairs both angiogenesis through ORP150 depletion and endoplasmic reticulum stress responses[J]. J Neuropathol Exp Neurol,2008,67(5):456-469. doi: 10.1097/NEN.0b013e318170f892
    [46] Raftopoulou M,Hall A. Cell migration: Rho GTPases lead the way[J]. Dev Biol,2004,265(1):23-32. doi: 10.1016/j.ydbio.2003.06.003
    [47] Tabu K,Ohba Y,Suzuki T,et al. Oligodendrocyte lineage transcription factor 2 inhibits the motility of a human glial tumor cell line by activating RhoA[J]. Mol Cancer Res,2007,5(10):1099-1109. doi: 10.1158/1541-7786.MCR-07-0096
    [48] Shieu M K,Ho H Y,Lin C C,et al. NCS suppresses oral cancer metastasis by modulating cathepsin B and extracellular signal-related kinase pathways[J]. Biomed Pharmacother,2023,158:114159. doi: 10.1016/j.biopha.2022.114159
    [49] Q Peng,Deng Z,Pan H,et al. Mitogen-activated protein kinase signaling pathway in oral cancer[J]. Oncol Lett,2018,15(2):1379-1388.
    [50] Gopalakrishnan R,Matta H,Choi S,et al. NCS,an isocarbostyril alkaloid,has preferential activity against primary effusion lymphoma[J]. Sci Rep,2020,10(1):5712. doi: 10.1038/s41598-020-62690-9
    [51] Meyer N,Penn L Z. Refecting on 25 years with MYC[J]. Nat Rev Cance,2008,8(12):976-990. doi: 10.1038/nrc2231
    [52] Tolani B,Gopalakrishnan R,Punj V,et al. Targeting Myc in KSHV-associated primary effusion lymphoma with BET bromodomain inhibitors[J]. Oncogene,2014,33(22):2928-2937. doi: 10.1038/onc.2013.242
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  • 收稿日期:  2023-05-05
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