浏览全部资源
扫码关注微信
山东中医药大学,济南 250355
Published:20 January 2022,
Published Online:04 November 2021,
Received:24 September 2021,
扫 描 看 全 文
牟悦,王彤,王雪振等.芸香苷抗肿瘤的基础作用机制研究进展[J].中国实验方剂学杂志,2022,28(02):249-256.
MOU Yue,WANG Tong,WANG Xue-zhen,et al.Antitumor Effect and Mechanism of Rutin: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(02):249-256.
牟悦,王彤,王雪振等.芸香苷抗肿瘤的基础作用机制研究进展[J].中国实验方剂学杂志,2022,28(02):249-256. DOI: 10.13422/j.cnki.syfjx.20220125.
MOU Yue,WANG Tong,WANG Xue-zhen,et al.Antitumor Effect and Mechanism of Rutin: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(02):249-256. DOI: 10.13422/j.cnki.syfjx.20220125.
癌症的发病率和死亡率不断上升,已成为威胁全球人类健康的首要危险因素,癌症的防治一直是困扰世界各国学者的难题,由于化疗药物有较强的不良反应,严重影响癌症患者的生活质量。因此,寻找安全有效且毒不良反应小的抗癌药物已迫在眉睫。近年来,传统药物的抗癌作用备受关注,随着医疗科研水平的发展,越来越多的抗癌活性成分从传统药物中提取出来,且不良反应较低,抗癌效果良好。芸香苷是一种独特的类黄酮,存在于许多植物中。研究发现芸香苷能抑制乳腺癌、结肠癌、肺癌、前列腺癌等肿瘤细胞的增殖。此外,已有报道芸香苷单独或与其他治疗药物联合可调节多种信号通路及各种炎症、凋亡、自噬和血管生成等信号介质,从而抑制肿瘤进展,而且芸香苷还能降低肿瘤耐药性和化疗药物的不良反应。尽管其具有强大的抗癌潜力,但生物利用度低、溶解度低等因素限制了其直接使用,而围绕芸香苷制备的纳米制剂可提高其作为抗癌成分的生物利用度和功效。目前对于芸香苷的抗癌潜力及在各类癌症中相关分子靶点的综合和分析略有缺乏,所以笔者检索了近年来关于芸香苷抗癌作用的文献,综述了其抗癌机制和分子靶点,并讨论了相关的药物递送及安全问题,为芸香苷的进一步开发和应用提供新的思路和理论基础。
The morbidity and mortality of cancer have been on the rise, making it atop the list of human health threats. It has been a conundrum of global magnitude. As the side effects of chemotherapeutics seriously affect the life quality of cancer patients, it is urgent to find effective anti-cancer drugs with small toxic and side effects. In recent years, the anti-cancer effects of traditional Chinese medicine have attracted the interest of scholars. Owing to the improvement of medical research, an increasing number of anti-cancer components with small toxic and side effects have been extracted from traditional Chinese medicine. Rutin, a unique flavonoid in Chinese medicinals and many plants, proves to inhibit the proliferation of breast cancer, colon cancer, lung cancer, and prostate cancer cells. In addition, rutin alone or in combination with other therapeutic drugs can regulate a variety of signaling pathways and signal mediators of inflammation, apoptosis, autophagy, and angiogenesis, thereby suppressing tumor progression. Moreover, it can also alleviate the drug resistance of tumors and the side effect of chemotherapeutics. Nevertheless, it is limited by the low bioavailability and low solubility, to which nano delivery system turns to be a solution. At the moment, the anti-cancer potential of rutin and the molecular targets of it against various cancers have not been summarized and comprehensively analyzed. Therefore, the authors retrieved articles on the anti-cancer effects of rutin in recent years, summed up the mechanisms and molecular targets, and discussed relevant drug delivery systems and the safety, aiming at laying a theoretical foundation for further development and application of the flavonoid.
芸香苷肿瘤抗癌活性作用机制
rutintumoranti-cancer activityaction mechanism
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 Cancer J Clin, 2021, 71(3): 209-249.
臧志和, 曹丽萍, 钟铃. 芦丁药理作用及制剂的研究进展 [J]. 医药导报, 2007, 26(7): 758-760.
刘芳. 中药桑叶中主要成分的含量测定的研究进展 [J]. 天津药学, 2018, 30(2): 53-57.
张寒, 徐远涛, 刘杰, 等. 小蓟中芦丁、蒙花苷、木犀草素和芹菜素一测多评方法的建立 [J]. 国际药学研究杂志, 2019, 46(10): 785-789.
FARHA A K, GAN R Y, LI H B, et al. The anticancer potential of the dietary polyphenol rutin: Current status, challenges, and perspectives [J]. Crit Rev Food Sci Nutr, 2020, doi:10.1080/10408398.2020.1829541http://dx.doi.org/10.1080/10408398.2020.1829541.
WILLIAMS R, SPENCER J, RICE-EVANS C. Flavonoids: antioxidants or signalling molecules? [J]. Free Radical Bio Med, 2004, 36(7): 838-849.
DE OLIVEIRA C T P, COLENCI R, PACHECO C C, et al. Hydrolyzed rutin decreases worsening of anaplasia in glioblastoma relapse [J]. CNS Neurol Disord Drug Targets, 2019, 18(5): 405-412.
MAGALINGAM K B, RADHAKRISHNAN A, HALEAGRAHARA N. Rutin, a bioflavonoid antioxidant protects rat pheochromocytoma (PC-12) cells against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity [J]. Int J Mol Med, 2013, 32(1): 235-240.
GONZÁLEZ-GALLEGO J, SÁNCHEZ-CAMPOS S, TUÑÓN M J. Anti-inflammatory properties of dietary flavonoids [J]. Nutr Hosp, 2007, 22(3): 287-293.
SATARI A, GHASEMI S, HABTEMARIAM S, et al. Rutin: a flavonoid as an effective sensitizer for anticancer therapy; insights into multifaceted mechanisms and applicability for combination therapy [J]. Evid Based Complement Alternat Med, 2021, doi:10.1155/2021/9913179http://dx.doi.org/10.1155/2021/9913179.
PANDEY P, RAHMAN M, BHATT P, et al. Implication of nano-antioxidant therapy for treatment of hepatocellular carcinoma using PLGA nanoparticles of rutin [J]. Nanomedicine, 2018, 13(8): 849-870.
CAPARICA R, JULIO A, ARAUJO M E M, et al. Anticancer activity of rutin and its combination with ionic liquids on renal cells [J]. Biomolecules, 2020, 10(2): 233.
GUON T E, CHUNG H S. Hyperoside and rutin of Nelumbo nucifera induce mitochondrial apoptosis through a Caspase-dependent mechanism in HT-29 human colon cancer cells [J]. Oncol Lett, 2016, 11(4): 2463-2470.
HANAHAN D, WEINBERG R. Hallmarks of cancer: the next generation [J]. Cell, 2011, 144(5): 646-674.
BHARATHI D, RANJITHKUMAR R, CHANDARSHEKAR B, et al. Bio-inspired synthesis of chitosan/copper oxide nanocomposite using rutin and their anti-proliferative activity in human lung cancer cells [J]. Int J Biol Macromol, 2019, doi:10.1016/j.ijbiomac.2019.08.235http://dx.doi.org/10.1016/j.ijbiomac.2019.08.235.
PAUDEL K R, WADHWA R, TEW X N, et al. Rutin loaded liquid crystalline nanoparticles inhibit non-small cell lung cancer proliferation and migration in vitro [J]. Life Sci, 2021, doi:10.1016/j.lfs.2021.119436http://dx.doi.org/10.1016/j.lfs.2021.119436.
DE ARAUJO M E, MOREIRA FRANCO Y E, ALBERTO T G, et al. Enzymatic de-glycosylation of rutin improves its antioxidant and antiproliferative activities [J]. Food Chem, 2013, 141(1): 266-273.
高蕊, 何东宁, 王亚帝, 等. 芦丁通过Notch信号通路抑制结肠癌细胞增殖 [J]. 中国老年学杂志, 2019, 39(5): 1192-1194.
沈钦海, 马臻, 陈国民. 芦丁对HepG2细胞生长的影响 [J]. 第三军医大学学报, 2006, 28(18): 1885-1887.
LIN J P, YANG J S, LU C C, et al. Rutin inhibits the proliferation of murine leukemia WEHI-3 cells in vivo and promotes immune response in vivo [J]. Leuk Res, 2009, 33(6): 823-828.
LIN J P, YANG J S, LIN J J, et al. Rutin inhibits human leukemia tumor growth in a murine xenograft model in vivo [J]. Environ Toxicol, 2012, 27(8): 480-484.
XU Z, SONG Y, WANG F. Rational design of genetically encoded reporter genes for optical imaging of apoptosis [J]. Apoptosis, 2020, 25(7/8): 459-473.
YAACOUB K, PEDEUX R, TARTE K, et al. Role of the tumor microenvironment in regulating apoptosis and cancer progression [J]. Cancer Lett, 2016, 378(2): 150-159.
SALEH A, ELFAYOUMI H M, YOUNS M, et al. Rutin and orlistat produce antitumor effects via antioxidant and apoptotic actions [J]. Naunyn Schmiedebergs Arch Pharmacol, 2019, 392(2): 165-175.
ELMORE S. A review of programmed cell death [J]. Toxicol Pathol, 2007, 35(4): 495-516.
李琪, 任立群, 王亚帝, 等. 芦丁联合奥沙利铂对人胃癌SGC-7901细胞增殖及凋亡的影响 [J]. 中国临床药理学与治疗学, 2017, 22(10): 1099-1105.
李琪, 任立群, 王亚帝, 等. 芦丁联合奥沙利铂激活FKN/SYK/p38通路促进胃癌细胞凋亡 [J]. 肿瘤防治研究, 2017, 44(11): 719-723.
陈立军, 靳秋月, 王玮, 等. 芸香苷诱导Caspase-3在白血病细胞凋亡时的表达 [J]. 武警医学院学报, 2007, 16(6): 604-606,592.
陈立军, 靳秋月, 王瑞珉, 等. 芸香苷诱导K562细胞凋亡机制 [J]. 中草药, 2006, 37(5): 738-741.
SATARI A, AMINI S A, RAEISI E, et al. Synergetic impact of combined 5-fluorouracil and rutin on apoptosis in PC3 cancer cells through the modulation of p53 gene expression [J]. Adv Pharm Bull, 2019, 9(3): 462-469.
AHMAD M, SAHABJAD A, AKHTAR J, et al. Development of a new rutin nanoemulsion and its application on prostate carcinoma PC3 cell line [J]. Excli J, 2017, doi:10.17179/excli2016-668http://dx.doi.org/10.17179/excli2016-668.
RADWAN R R, ALI H E. Radiation-synthesis of chitosan/poly (acrylic acid) nanogel for improving the antitumor potential of rutin in hepatocellular carcinoma [J]. Drug Deliv Transl Res, 2021, 11(1): 261-278.
KHAN F, PANDEY P, JHA N K, et al. Rutin mediated apoptotic cell death in caski cervical cancer cells via Notch-1 and Hes-1 downregulation [J]. Life (Basel), 2021, 11(8): 761-761.
KHAN F, PANDEY P, UPADHYAY T K, et al. Anti-cancerous effect of rutin against HPV-C33A cervical cancer cells via G0/G1 cell cycle arrest and apoptotic induction [J]. Endocr Metab Immune Disord Drug Targets, 2020, 20(3): 409-418.
PANDEY P, KHAN F, FARHAN M, et al. Elucidation of rutin's role in inducing Caspase-dependent apoptosis via HPV-E6 and E7 down-regulation in cervical cancer HeLa cells [J]. Biosci Rep, 2021, 41(6): BSR20210670.
CHEN H, MIAO Q, GENG M, et al. Anti-tumor effect of rutin on human neuroblastoma cell lines through inducing G2/M cell cycle arrest and promoting apoptosis [J]. Sci World J, 2013, doi:10.1155/2013/269165http://dx.doi.org/10.1155/2013/269165.
LI Q, REN L, ZHANG Y, et al. P38 signal transduction pathway has more cofactors on apoptosis of SGC-7901 gastric cancer cells induced by combination of rutin and oxaliplatin [J]. Biomed Res Int, 2019, doi:10.1155/2019/6407210http://dx.doi.org/10.1155/2019/6407210.
WU F, CHEN J, FAN L M, et al. Analysis of the effect of rutin on GSK-3beta and TNF-alpha expression in lung cancer [J]. Exp Ther Med, 2017, 14(1): 127-130.
NASRI NASRABADI P, ZAREIAN S, NAYERI Z, et al. A detailed image of rutin underlying intracellular signaling pathways in human SW480 colorectal cancer cells based on miRNAs-lncRNAs-mRNAs-TFs interactions [J]. J Cell Physiol, 2019, doi:10.1002/jcp.28204http://dx.doi.org/10.1002/jcp.28204.
NAFEES S, MEHDI S H, ZAFARYAB M, et al. Synergistic interaction of rutin and silibinin on human colon cancer cell line [J]. Arch Med Res, 2018, 49(4): 226-234.
FRIEDL P, WOLF K. Tumour-cell invasion and migration: diversity and escape mechanisms [J]. Nat Rev Cancer, 2003, 3(5): 362-374.
ENTSCHLADEN F, DRELL T, LANG K, et al. Tumour-cell migration, invasion, and metastasis: navigation by neurotransmitters [J]. Lancet Oncol, 2004, 5(4): 254-258.
KARAKURT S. Modulatory effects of rutin on the expression of cytochrome P450s and antioxidant enzymes in human hepatoma cells [J]. Acta Pharm, 2016, 66(4): 491-502.
CONESA C M, ORTEGA V V, YáEZGASCóN M J, et al. Treatment of metastatic melanoma B16F10 by the flavonoids tangeretin, rutin, and diosmin [J]. J Agric Food Chem, 2005, 53(17): 6791-6797.
SANTOS B L, OLIVEIRA M N, COELHO P L, et al. Flavonoids suppress human glioblastoma cell growth by inhibiting cell metabolism, migration, and by regulating extracellular matrix proteins and metalloproteinases expression [J]. Chem Biol Interact, 2015, doi:10.1016/j.cbi.2015.07.014http://dx.doi.org/10.1016/j.cbi.2015.07.014.
DA SILVA A B, CERQUEIRA COELHO P L, DASNEVES OLIVEIRA M, et al. The flavonoid rutin and its aglycone quercetin modulate the microglia inflammatory profile improving antiglioma activity [J]. Brain Behav Immun, 2020, doi:10.1016/j.bbi.2019.05.003http://dx.doi.org/10.1016/j.bbi.2019.05.003.
ELSAYED H E, EBRAHIM H Y, MOHYELDIN M M, et al. Rutin as a novel c-Met inhibitory lead for the control of triple negative breast malignancies [J]. Nutr Cancer, 2017, 69(8): 1256-1271.
LI Q, XU D, GU Z, et al. Rutin restrains the growth and metastasis of mouse breast cancer cells by regulating the microRNA-129-1-3p-mediated calcium signaling pathway [J]. J Biochem Mol Toxicol, 2021, 35(7): e22794.
ARETI A, KOMIRISHETTY P, AKUTHOTA M, et al. Melatonin prevents mitochondrial dysfunction and promotes neuroprotection by inducing autophagy during oxaliplatin-evoked peripheral neuropathy [J]. J Pineal Res, 2017, doi:10.1111/jpi.12393http://dx.doi.org/10.1111/jpi.12393.
AZEVEDO M, PEREIRA A, NOGUEIRA R, et al. The antioxidant effects of the flavonoids rutin and quercetin inhibit oxaliplatin-induced chronic painful peripheral neuropathy [J]. Mol Pain, 2013, doi:10.1186/1744-8069-9-53http://dx.doi.org/10.1186/1744-8069-9-53.
ALIA M, MATEOS R, RAMOS S, et al. Influence of quercetin and rutin on growth and antioxidant defense system of a human hepatoma cell line (HepG2) [J]. Eur J Nutr, 2006, 45(1): 19-28.
EMADI A, JONES R, BRODSKY R. Cyclophosphamide and cancer: golden anniversary [J]. Nat Rev Clin Oncol, 2009, 6(11): 638-647.
NAFEES S, RASHID S, ALI N, et al. Rutin ameliorates cyclophosphamide induced oxidative stress and inflammation in Wistar rats: role of NF kappaB/MAPK pathway [J]. Chem Biol Interact, 2015, doi:10.1016/j.cbi.2015.02.021http://dx.doi.org/10.1016/j.cbi.2015.02.021.
QI L, LUO Q, ZHANG Y, et al. Advances in toxicological research of the anticancer drug cisplatin [J]. Chem Res Toxicol, 2019, 32(8): 1469-1486.
PRASAD R, PRASAD S B. Histoprotective effect of rutin against cisplatin-induced toxicities in tumor-bearing mice: Rutin lessens cisplatin-induced toxicities [J]. Hum Exp Toxicol, 2021, 40(2): 245-258.
WANG C, ZHAO Y, WANG L, et al. C-phycocyanin mitigates cognitive impairment in doxorubicin-induced chemobrain: impact on neuroinflammation, oxidative stress, and brain mitochondrial and synaptic alterations [J]. Neurochem Res, 2021, 46(2): 149-158.
RAMALINGAYYA G V, GOURISHETTI K, NAYAK P G, et al. Rutin protects against doxorubicin-induced cognitive dysfunction while retaining its anticancer potential in a murine model of N-methyl-N-nitrosourea-induced mammary carcinoma [J]. J Environ Pathol Toxicol Oncol, 2019, 38(2): 153-163.
VIJAY M, SIVAGAMI G, THAYALAN K, et al. Radiosensitizing potential of rutin against human colon adenocarcinoma HT-29 cells [J]. Bratisl Lek Listy, 2016, 117(3): 171-178.
BELLAMY W, RICHTER L, FRUTIGER Y, et al. Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies [J]. Cancer Res, 1999, 59(3): 728-733.
CHUANG C H, HUANG C S, HU M L. Vitamin E and rutin synergistically inhibit expression of vascular endothelial growth factor through down-regulation of binding activity of activator protein-1 in human promyelocytic leukemia (HL-60) cells [J]. Chem Biol Interact, 2010, 183(3): 434-441.
ALONSO-CASTRO A J, DOMINGUEZ F, GARCIA-CARRANCA A. Rutin exerts antitumor effects on nude mice bearing SW480 tumor [J]. Arch Med Res, 2013, 44(5): 346-351.
VANDERBIJ G J, BOGELS M, OOSTERLING S J, et al. Tumor infiltrating macrophages reduce development of peritoneal colorectal carcinoma metastases [J]. Cancer Lett, 2008, 262(1): 77-86.
CHATTERJEE N, BIVONA T G. Polytherapy and targeted cancer drug resistance[J].Trends Cancer, 2019, 5(3):170-182.
IRITI M, KUBINA R, COCHIS A, et al. Rutin, a quercetin glycoside, restores chemosensitivity in human breast cancer cells [J]. Phytother Res, 2017, 31(10): 1529-1538.
王婷婷, 刘超怡, 李秀芬, 等. 芸香苷逆转人大肠癌LoVo/5-氟尿嘧啶细胞耐药性及其机制 [J]. 解剖学报, 2020, 51(6): 906-911.
IMANI A, MALEKI N, BOHLOULI S, et al. Molecular mechanisms of anticancer effect of rutin [J]. Phytother Res, 2020; 10.1002/ptr.6977. doi:10.1002/ptr.6977http://dx.doi.org/10.1002/ptr.6977.
SHARMA S, ALI A, ALI J, et al. Rutin: therapeutic potential and recent advances in drug delivery: Expert Opinion On Investigational Drugs: Vol 22, No 8 [J]. Expert Opin Investig Drugs, 2013, 22(8):1063-1079.
0
Views
16
下载量
2
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution