小檗碱及其衍生物抗肿瘤作用研究进展

方慧华, 李洪娇, 何小蕾, 姜远英, 曹永兵, 许激扬

中国药学杂志 ›› 2017, Vol. 52 ›› Issue (6) : 429-433.

PDF(1242 KB)
PDF(1242 KB)
中国药学杂志 ›› 2017, Vol. 52 ›› Issue (6) : 429-433. DOI: 10.11669/cpj.2017.06.001
综述

小檗碱及其衍生物抗肿瘤作用研究进展

  • 方慧华1,2, 李洪娇3, 何小蕾1,2, 姜远英2, 曹永兵2, 许激扬1*
作者信息 +

Recent Research Advances in Anti-Tumor Effects of Berberine and Its Derivatives

  • FANG Hui-hua1,2, LI Hong-jiao3, HE Xiao-lei1,2, JIANG Yuan-ying2, CAO Yong-bing2, XU Ji-yang1*
Author information +
文章历史 +

摘要

小檗碱(berberine)属于季铵型异喹啉类生物碱,又称黄连素。临床上用于治疗由细菌感染引起的胃肠道疾病。近年来研究发现,小檗碱具有良好的抗肿瘤作用,但由于其脂溶性差,难以透过细胞膜,限制了其临床应用。在此基础上,一些研究者通过对其化学结构进行改造和修饰,研究其各种药理作用的构效关系,发现了一系列抗肿瘤活性得到增强的衍生物。笔者主要综述小檗碱及其衍生物在抗肿瘤作用及其机制方面的研究进展,为基于小檗碱结构设计开发抗肿瘤药的研究者提供参考。

Abstract

Berberine belongs to the quaternary ammonium type isoquinoline alkaloid known as berberinum. In traditional Chinese medicine, it has long been used to treat infections of the gastrointestinal tract disease caused by bacteria.Recent studies found that berberine has a good anti-tumor effect,but it is difficult pass through the cell membrane due to its poor fat-soluble,which limit its clinical application. By modifing chemical structure,some researchers have investigated the relationship between activity effects and structures of berberine and its derivatives, and have found a series of anti-tumor activity enhanced berberine derivatives.In this review, the recent research progress of the anti-tumor effects and their mechanisms of berberine and its derivatives are focused, which may provide reference for the design and development of anticancer drugs based on the structure of berberine

关键词

小檗碱 / 小檗碱衍生物 / 抗肿瘤 / 作用机制

Key words

berberine / berberine derivatives / anti-tumor / mechanism

引用本文

导出引用
方慧华, 李洪娇, 何小蕾, 姜远英, 曹永兵, 许激扬. 小檗碱及其衍生物抗肿瘤作用研究进展[J]. 中国药学杂志, 2017, 52(6): 429-433 https://doi.org/10.11669/cpj.2017.06.001
FANG Hui-hua, LI Hong-jiao, HE Xiao-lei, JIANG Yuan-ying, CAO Yong-bing, XU Ji-yang. Recent Research Advances in Anti-Tumor Effects of Berberine and Its Derivatives[J]. Chinese Pharmaceutical Journal, 2017, 52(6): 429-433 https://doi.org/10.11669/cpj.2017.06.001
中图分类号: R965   

参考文献

[1] ZHONG C P, QIAN Y, SHU C, et al. Research progress in antimicrobial effects of berberine and its derivatives[J]. Food Sci(食品科学),2013,34(7):321-325.
[2] ANSARI N, KHODAGHOLI F. Natural products as promising drug candidates for the treatment of Alzheimer’s disease: molecular mechanism aspect[J]. Curr Neuropharmacol, 2013,11(4):414-429.
[3] JANTOVA S, CIPAK L, CERNAKOVA M, et al. Effect of berberine on proliferation, cell cycle and apoptosis in HeLa and L1210 cells[J]. J Pharm Pharmacol, 2003, 55(8):1143-1149.
[4] YU F S, YANG J S, LIN H J, et al. Berberine inhibits WEHI-3 leukemia cells in vivo[J]. In Vivo,2007,21(2):407-412.
[5] HO Y T, YANG J S, LU C C, et al. Berberine inhibits human tongue squamous carcinoma cancer tumor growth in a murine xenograft model[J]. Phytomedicine,2009,16(9):887-890.
[6] LETASIOV S, JANTOV S, CIP K L, et al. Berberine-antiproliferative activity in vitro and induction of apoptosis/necrosis of the U937 and B16 cells[J]. Cancer Lett,2006,239(2):254-262.
[7] LIN C C, YANG J S, CHEN J T, et al. Berberine induces apoptosis in human HSC-3 oral cancer cells via simultaneous activation of the death receptor-mediated and mitochondrial pathway[J]. Anticancer Res,2007,27(5A):3371-3378.
[8] DUBOIS R N, ABRAMSON S B, CROFFORD L, et al. Cyclooxygenase in biology and disease[J]. FASEB J, 1998,12(12):1063-1073.
[9] ANIS K V, RAJESHKUMAR N V, KUTTAN R. Inhibition of chemical carcinogenesis by berberine in rats and mice[J]. J Pharm Pharmacol, 2001, 53(5):763-768.
[10] YANG I W, CHOU C C, YUNG B Y M. Dose-dependent effects of berberine on cell cycle pause and apoptosis in Balb/c 3T3 cells[J]. Naunyn Schmiedeberg Arch Pharmacol,1996,354(2):102-108.
[11] MURTHY K N C, PATIL B S. The natural alkaloid berberine targets multiple pathways to induce cell death in cultured human colon cancer cells[J]. Eur J Pharmacol, 2012, 688(1-3):14-21.
[12] WU H L, CHEN Y H, LIU W H, et al. Berberine-induced apoptosis of human leukemia HL-60 cells is associated with down-regulation of nucleophosmin/B23 and telomerase activity[J]. Int J Cancer,1999, 81(6):923-929.
[13] QI H W, XIN L Y, XU X, et al. Epithelial-to-mesenchymal transition markers to predict response of berberine in suppressing lung cancer invasion and metastasis[J]. J Translat Med, 2014,12(1):116-122.
[14] LIN S, TSAI S C, LEE C C, et al. Berberine inhibits HIF-1alpha expression via enhanced proteolysis[J]. Mol Pharmacol,2004,66(3):612-619.
[15] KIM S, CHOI J H, KIM J B, et al. Berberine suppresses TNF-alpha-induced MMP-9 and cell invasion through inhibition of AP-1 activity in MDA-MB-231 human breast cancer cells[J]. Molecules,2008, 13(12):2975-2985.
[16] HAMSA T P, KUTTAN G. Berberine inhibits pulmonary metastasis through down-regulation of MMP in metastatic B16F-10 melanoma cells[J]. Phytothera Res,2012, 26(4):568-578.
[17] JIN P, ZHANG C, LI N. Berberine exhibits antitumor effects in human ovarian cancer cells[J]. Anticancer Agents Med Chem,2015,15(4):511-516.
[18] ZHU T, LI L L, XIAO G F, et al. Berberine increases doxorubicin sensitivity by suppressing STAT3 in lung cancer[J]. Am J Chin Med,2015, 43(7):1478-1502.
[19] YU M, TONG X, QI B, et al. Berberine enhances chemosensitivity to irinotecan in colon cancer via inhibition of NFκB[J]. Mol Med Rep,2014,9(1):249-254.
[20] KUO H P, CHUANG T C, YEH M H, et al. Growth suppression of HER2-overexpressing breast cancer cells by berberine via modulation of the HER2/PI3K/Akt signaling pathway[J]. J Agricul Food Chem,2011,59(15):8216-8224.
[21] JIANG G, LI L, WU X, et al. Influence of berberine on cisplatin antineoplastic effect in A549 cells[J]. Chin J Lung Cancer(中国肺癌杂志),2015,18(8):481-486.
[22] KOBAYASHI Y, YAMASHITA Y N, TAKABOSHI K, et al. Inhibitors of DNA topoisomerase i and ii isolated from the coptis rhizomes[J]. Planta Med,1995,61(5):414-418.
[23] JIN X, SONG X, CAO Y, et al. Research progress in structural modification and pharmacological activities of berberine[J]. J Pharm Pract(药学实践杂志),2014,32(3):171-175.
[24] HOSHI A, IKEKAWA T, IKEDA Y, et al. Antitumor activity of berberrubine derivatives[J]. Gan, 1976,67(2):321-325.
[25] MA Y, OU T M, HOU J Q, et al. 9-N-Substituted berberine derivatives: stabilization of G-quadruplex DNA and down-regulation of oncogene c-myc[J]. Bioorg Med Chem,2008, 16(16):7582-7591.
[26] YAN M A, HUANG Z S. Synthesis and activity evaluation of 9-O-substituted berberine derivatives containing polyamine chain as highly selective telomeric G-quadruplex stabilizing ligands[J]. Chem J Chin Univ(高等学校化学学报),2012,33(10):2217-2222.
[27] LO C Y,HSU L C,CHEN M S,et al.Synthesis and anticancer activity of a novel series of 9-O-substituted berberine derivatives:a lipophilic substitute role[J].Bioorg Med Chem Lett,2013,23(1):305-309.
[28] PANG J Y,QIN Y,CHEN W H,et al.Synthesis and DNA-binding affinities of monomodified berberines[J].Bioorg Med Chem,2005,13(20):5835-5840.
[29] CHEN W H,PANG J Y,QIN Y,et al.Synthesis of linked berberine dimers and their remarkably enhanced DNA-binding affinities[J]. Bioorg Med Chem Lett,2005,15(10):2689-2692.
[30] LI Q Y,ZU Y G,LIU T Y,et al.Generation of reactive oxygen species by a novel berberine-bile acid analog mediates apoptosis in hepatocarcinoma SMMC-7721 cells[J]. Biochem Biophys Res Commun,2013,433(4):432-437.
[31] XIAO N, CHEN S, MA Y, et al. Interaction of berberine derivative with protein POT1 affect telomere function in cancer cells[J]. Biochem Biophys Res Commun, 2012,419(3):567-572.
[32] JIN X, YAN T H, YAN L, et al. Design, synthesis, and anticancer activity of novel berberine derivatives prepared via CuAAC “click” chemistry as potential anticancer agents[J]. Drug Des Devel Ther,2014,8:1047-1059.
[33] JIN X, YAN L, LI H J, et al. Novel triazolyl berberine derivatives prepared via CuAAC click chemistry: synthesis, anticancer activity and structure-activity relationships[J]. Anticancer Agents Med Chem,2014, 15(1):89-98.
[34] ZHANG L, LI J, MA F, et al. Synthesis and cytotoxicity evaluation of 13-n-alkyl berberine and palmatine analogues as anticancer agents[J]. Molecules, 2012,17(10):11294-11302.
[35] ZHAO W L, LI Y B, LI Y H, et al. Synthesis and structure-activity relationship of 13-substituted berberine derivatives as anti-cancer agents[J]. Chin Med Rep(中国医药导报), 2013,10(18):17-20.
[36] GUAMAN ORTIZ L M, TILLHON M, PARKS M, et al. Multiple effects of berberine derivatives on colon cancer cells[J]. Biomed Res Int,2014,2014(2):924585-924585.
[37] PIERPAOLI E, DAMIANI E, ORLANDO F, et al. Antiangiogenic and antitumor activities of berberine derivative NAX014 compound in a transgenic murine model of HER2/neu-positive mammary carcinoma[J]. Carcinogenesis,2015, 36(10):1169-1179.[38] FRANCESCHIN M,ROSSETTI L,D'AMBROSIO A,et al.Natural and synthetic G-quadruplex interactive berberine derivatives[J].Bioorg Med Chem Lett,2006,16(6):1707-1711.
[39] GORNALL K C,SAMOSOM S,TALIB J,et al. Selectivity of an indolyl berberine derivative for tetrameric G-quadruplex DNA[J].Rapid Commun Mass Spectrom,2007,21(11):1759-1766.

基金

国家自然科学基金资助项目(81273556,81673478)
PDF(1242 KB)

Accesses

Citation

Detail

段落导航
相关文章

/