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化学进展 2011, Vol. 23 Issue (5): 983-990 前一篇   后一篇

• 综述与评论 •

钌配合物诱导肿瘤细胞凋亡的信号通路及其作用机制

张小年, 刘亚楠, 杨晓新, 刘杰   

  1. 暨南大学 生命科学技术学院化学系 广州 510632
  • 收稿日期:2010-08-01 修回日期:2010-10-01 出版日期:2011-05-24 发布日期:2011-05-04
  • 基金资助:

    国家自然科学基金项目(No.20871056)、广东省科技计划项目(No.c1011220800060)和中央高校基本科研业务费专项资金资助

Apoptotic Signal Pathways of Tumor Cells Induced by Ruthenium Complexes and Its Mechanisms

Zhang Xiaonian, Liu Yanan, Yang Xiaoxin, Liu Jie   

  1. Department of Chemistry, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
  • Received:2010-08-01 Revised:2010-10-01 Online:2011-05-24 Published:2011-05-04

钌配合物作为抗癌药物的研究已经受到了国际研究者的广泛关注。近年来,新型结构钌配合物的设计合成;钌配合物在细胞凋亡、信号传递、基因、蛋白表达等过程中的调控作用成为新的研究热点,金属钌配合物抗癌活性机制得到进一步的阐释。本文主要对钌配合物诱导肿瘤细胞凋亡及其信号通路以及蛋白调控等抗肿瘤机制的研究进行评述。主要包括:已经进入临床(Ⅰ、Ⅱ)期的抗癌钌配合物的抗肿瘤机制;钌配合物阻滞肿瘤细胞周期;通过内源性线粒体损伤、内质网应激等信号转导通路诱导肿瘤细胞凋亡,调节肿瘤细胞凋亡途径中相关蛋白的表达;调控与细胞凋亡或增殖相关蛋白酶类的表达和活性等。

As anticancer drugs, ruthenium complexes have received wide attention at home and abroad.In recent years, the design and synthesis of new types of complexes,the regulatory role of complexes in apoptosis, signal transduction, and gene expression have become a new hotspot, and its mechanisms of anticancer activity of metal complexes have been further explained. This paper mainly reviews ruthenium complexes, including their effect to induce the apoptosis of various types of tumor cell and their mechanism that induces apoptosis in current studies. The main text includes the following: the anti-cancer mechanism of the ruthenium complexes which had accessed to clinical (Ⅰ, Ⅱ); the cell cycle arrest induced by ruthenium complexes; the endogenous mitochondrial damage, the endoplasmic reticulum stress and other signal transduction pathway which induced tumor cell apoptosis; regulating the expression of the pathway-related proteins; regulating the expression and activity of these proteins which are related to the cell apoptosis or the cell proliferation.

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[1] Hideo F, Masaki Y, Takao A, Satoshi S, Shuzo S. Neuropharmacol., 1993, 32: 959-968
[2] Zhang C X, Lippard S. J. Curr. Opin. Chem. Biol., 2003, 7: 481-489
[3] Clark M. J. Coord. Chem. Rev., 2002, 232: 69-93
[4] Bergamo A, Sava G. Dalton. Trans., 2007, 1267-1272
[5] Sava G, Bergamo A, Zorzet S, Gava B, Casarsa C, Cocchietto M, Furlani A, Scarcia V, Serli B, Iengo E, Alessio E, Mestroni G. Eur. J. Cancer., 2002,38:427-435
[6] Bergamo A, Gagliardi R, Scarcia V, Furlani A, Alessio E, Mestroni G, Sava G. Pharm. Exp. Ther., 1999, 289: 559-564
[7] Serli B, Iengo E, Gianferrara T, Zangrando E, Alessio E. Metal Based Drugs., 2001, 8: 9-18
[8] Alessio E, Iengo E, Zorzet S, Bergamo A, Coluccia M, Boccarelli A, Sava G. J. Inorg. Biochem., 2000, 79: 157-161
[9] Sava G, Bergamo A. Zorzet S, Gava B, Casarsa C, Cocchietto M, Furlani A, Scarcia V, Serli B, Iengo E, Alessio E, Mestroni G, Eur. J. Cancer., 2002, 38: 427-435
[10] Kostova I. Curr. Med. Chem., 2006, 13: 1085-1107
[11] Hartinger C G, Zorbas-Seifried S, Jakupec M A, Zorbas H, Keppler B K. J. Inorg. Biochem., 2006, 100: 891-904
[12] Alessio E, Mestroni G, Bergamo A, Sava G, Curr. Top. Med. Chem., 2004, 4: 1525-1535
[13] Bergamo A, Gagliardi R, Scarcia V, Furlani A, Alessio E, Mestroni G, Sava G. J. Pharmacol. Exp. Ther., 1999, 289: 559-564
[14] Vacca A, Bruno M, Boccarelli A, Coluccia M, Ribatti D, Bergamo A, Garbisa S, Sartor L, Sava G. Br. J. Cancer, 2002, 86: 993-998
[15] Bergamo A, Sava G. Dalton Trans., 2007, 13: 1267-1272
[16] Chatterjee S, Kundu S, Bhattacharyya A, Hartinger C G, Dyson P J. J. Biol. Inorg. Chem., 2008, 13: 1149-1155
[17] Hayward R L, Schornagel Q C, Tente R, Macpherson J S, Aird R E, Guichard S, Habtemariam A, Sadler P, Jodrell D I. Cancer. Chemother. Pharmacol., 2005, 55: 577-583
[18] Gaiddon C, Jeannequin P, Bischoff P, Pfeffer M, Sirlin C, Loeffler J P. J. Pharmacol. Exp. Ther., 2005, 315: 1403-1411
[19] Bergamo A, Gagliardi R, Scarcia V, Furlani A, Alessio E, Mestroni G, Sava G. J. Pharmacol. Exp. Ther., 1999, 289: 559-564
[20] Das S, Sinha S, Britto R, Somasundaram K, Samuelson A G. J. Inorg. Biochem., 2010, 104: 93-104
[21] Liu Y N, Chen T F, Wong Y S, Mei W J, Huang X M, Yang F, Liu J, Zheng W J. Chemico-Biological Interactions, 2010, 183: 349-356
[22] Wang X D. Genes Dev., 2001, 15: 2922-2933
[23] Kapitza S, Pongratz M, Jakupec M A, Heffeter P, Berger W, Lackinger L, Keppler B K, Marian B. J. Cancer Res. Clin. Oncol., 2005, 131: 101-110
[24] 刘杰 (Liu J), 计亮年 (Ji L N), 梅文杰 (Mei W J). 化学进展(Progress in Chemistry), 2004, 16: 969-974
[25] Ang W H, Dyson P J. Eur. J. Inorg. Chem., 2006, 4003-4018
[26] Scolaro C, Bergamo A, Brescacin L, Delfino R, Cocchietto M, Laurenczy G, Geldbach T J, Sava G, Dyson P J. J. Med. Chem., 2005, 48: 4161-4171
[27] Scolaro C, Geldbach T J, Rochat S, Dorcier A, Gossens C, Bergamo A, Cocchietto M, Tavernelli I, Sava G, Rothlisberger U, Dyson P J. Organometallics, 2006, 25: 756-765
[28] Scolaro C, Chaplin A B, Hartinger C G, Bergamo A, Cocchietto M, Keppler B K, Sava G, Dyson P J. Dalton Trans., 2007, 43: 5065-5072
[29] Dorcier A, Dyson P J, Gossens C, Rothlisberger U, Scopelliti R, Tavernelli I. Organometallics, 2005, 24: 2114-2123
[30] Ang W H, Daldini E, Scolaro C, Scopelliti R, Juillerat J L, Dyson P J. Inorg. Chem., 2006, 45: 9006-9013
[31] Sava G, Bergamo A. Platinum and Other Heavy Metal Compounds in Cancer Chemotherapy, 2009. 57-66
[32] Morris R E, Aird R E, Murdoch P S, Chen H M, Cummings J, Hughes N D, Parsons S, Parkin A, Boyd G, Jodrell D I, Sadler P J. J. Med. Chem., 2001, 44: 3616-3621
[33] Smalley K S. M, Contractor R, Haass N K, Kulp A N, Gokcumen G E A, Williams D S, Bregman H, Flaherty K T, Soengas M S, Meggers E, Herlyn M. Cancer. Res., 2007, 67: 209-217
[34] Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T, Tanaka N. Science, 2000, 288: 1053-1058
[35] Chen T F, LiuY N, Zheng W J, Liu J, Wong Y S. Inorg. Chem., 2010, 49: 6366-6368
[36] Breckenridge D G. Germain M, Mathai J P, Nguyen M, Shore G C. Oncogene, 2003, 22: 8608-8618
[37] Kadowaki H, Nishitoh H, Chijo H I. J. Chem. Neuroanat., 2004, 28: 93-100
[38] Casini A, Gabbiani C, Sorrentino F, Rigobello M P, Bindoli A, Geldbach T J, Marrone A, Re N, Hartinger C G, Dyson P J, Messori L. J. Med. Chem., 2008, 51: 6773-6781
[39] Meng X G, Leyva M L, Jenny M, Gross I, Benosman S, Fricker B, Harlepp S, Heébraud P, Boos A, Wlosik P, Bischoff P, Sirlin C, Pfeffer M, Loeffler J P, Gaiddon C. Cancer Res., 2009, 69: 5458-5466
[40] Blume J P, Hunter T. Nature, 2001, 411: 355-365
[41] Tamaoki T, Nomoto H, Takahashi I, Kato Y, Morimoto M; Tomita F, Biochem. Biophys. Res. Commun., 1986, 135: 397-402
[42] Williams D S, Atilla G E, Bregman H, Arzoumanian A, Klein P S, Meggers E. Angew. Chem. Int. Ed. Engl., 2005, 44: 1984-1987
[43] Ghosh J C, Altieri D C. Clin. Cancer Res., 2005, 11: 4580-4588
[44] Tan T T, Degenhardt K, Nelson D A, Beaudoin B, Nieves-Neira W, Bouillet P, Villunger A, Adams J M, White E. Cancer Cell, 2005, 7: 227-238
[45] Pluquet O, Qu L K, Baltzis D, Koromilas A E. Mol. Cell Biol., 2005, 25: 9392-9405
[46] Kulikov R, Boehme K A, Blattner C. Mol. Cell. Biol., 2005, 25: 7170-7180
[47] 殷菲(Yin F), 刘建辉(Liu J H), 彭孝军(Peng X J). 化学通报(Chemistry), 2004, 4: 271-277
[48] Rajput C, Rutkaite R, Swanson L, Haq I, Thomas J A. Chem. Eur. J., 2006, 12: 4611-4619
[49] Shi S, Zhao J, Geng X T, Yao T M, Huang H L, Liu T L, Zheng L F, Li Z H, Yang D J, Ji L N. Dalton Trans., 2010, 39: 2490-2493
[50] Xu L, Zhang D, Huang J, Deng M G, Zhang M, Zhou X. Chem. Commun., 2010, 743-745
[51] Rickling S, Ghisdavu L, Pierard F, Gerbaux P, Surin M, Murat P, Defrancq E, Moucheron C, de Mesmaeker A K. Chem. Eur. J., 2010, 16: 3951-3961
[52] Shi S, Liu J, Yao T M, Geng X T, Jiang L F, Yang Q Y, Cheng L, Ji L N. Inorg. Chem., 2008, 47: 2910-2912
[53] Mei W J, Wei X Y, Liu Y J, Wang B. Transition. Met. Chem., 2008, 33: 907-910
[54] Malonne H, Atassi G. Anti-Cancer Drugs, 1997, 8: 811-822
[55] Vashisht G Y N, Jayaraju D, Kondapi A K. Biochemistry, 1999, 38: 4382-4388
[56] Vashisht G Y N, Kondapi A K. J. Biosci., 2001, 26: 271-276
[57] Gao F, Chao H, Wang J Q, Yuan Y X, Sun B, Wei Y F, Peng B, Ji L N. J. Bio. Inorg. Chem., 2007, 12: 1015-1027
[58] Gao F, Chao H, Zhou F, Chen X, Wei Y F, Ji L N. J. Inorg. Biochem., 2008, 102: 1050-1059
[59] Sharma S, Singh S K, Pandey D S. Inorg. Chem., 2008, 47: 1179-1189
[60] Singh S K, Joshi S, Singh A R, Saxena J K, Pandey D S. Inorg. Chem., 2007, 46: 10869-10876
[61] Loughrey B T, Williams M L, Healy P C, Innocenti A, Vullo D, Supuran C T, Parsons P G, Poulsen S A. J. Biol. Inorg. Chem., 2009, 14: 935-945
[62] Zhang L L, Carroll P, Meggers E. Org. Lett., 2004, 6: 521-523

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