Effective molecular mechanisms of resistance to cisplatin

Abstract

Effective molecular mechanisms of resistance to cisplatinCisplatin is a platinating chemotherapeutic agent widely used in the treatment of many solid tumors. It wasdiscovered for the first time as a growth inhibitor of Escherichia coli in 1970, later years its anticancer effectsrediscovered and began to use in the treatment of testicular, ovarian, cervical, head and neck, non-small celllung cancers and lymphoma. Although a good response to cisplatin can be achieved in the treatment oftesticular cancer, therapeutic efficacy is limited due to toxicity or drug resistance in other solid tumors. Inthis review the molecular mechanisms trough the development of cisplatin resistance and the new treatmentstrategies were evaluated. Understanding the molecular mechanisms of cisplatin resistancewill providesimportant insights for designingmore efficient platinum-based chemotherapeutics

Keywords

• Cisplatin resistance
• DNA damage
• DNA repair
• translesion synthesis
• apoptosis

CİSPLATİN DİRENCİNDE ETKİLİ MOLEKÜLER MEKANİZMALAR

Abstract

Cisplatin birçok solid tümörün tedavisinde sıklıkla kullanılan platin bileşiği bir kemoterapotik ajandır. İlk defa 1970 yılında Escherichia coli' nin büyüme inhibitörü olarak keşfedilmiş, daha sonraki yıllarda anti kanser etkisi fark edilerek testis, over, serviks, baş ve boyun, küçük hücreli dışı akciğer ve lenfoma tedavisinde kullanılmaya başlanmıştır. Testis kanserlerinde cisplatine genellikle iyi yanıt alınabilmesine karşılık diğer solid tümörlerde toksisite veya ilaç direnci nedeniyle terapötik etkinlik sınırlı kalmaktadır. Bu derlemede cisplatin yanıtının oluşmasını sağlayan biyokimyasal yolaklar, direnç gelişiminde etkili moleküler mekanizmalar ve yeni tedavi stratejileri değerlendirilmiştir. Cisplatin direnci gelişimindeki moleküler mekanizmaların anlaşılması daha efektif platin bazlı kemoterapotiklerin geliştirilmesi için önemli bilgiler sağlayacaktır.

Keywords

• Cisplatin direnci
• DNA hasarý
• DNA onarýmý
• translezyon sentezi
• apoptoz

References

1. Wang D, Lippard SJ. Cellular processing of platinum anticancer drugs. Nat Rev Drug Discov. 2005;4(4):307- 20.
2. Kuo MT, Chen HH, Song IS, Savaraj N, Ishikawa T. The roles of copper transporters in cisplatin resistance. Cancer Metastasis Rev. 2007;26(1):71-83. Epub 2007/02/24.
3. Zorbas H, Keppler BK. Cisplatin damage: are DNA repair proteins saviors or traitors to the cell? Chembiochem. 2005;6(7):1157-66.
4. Fuertes MA, Alonso C, Perez JM. Biochemical modulation of Cisplatin mechanisms of action: enhancement of antitumor activity and circumvention of drug resistance. Chem Rev. 2003;103(3):645-62.
5. Kartalou M, Essigmann JM. Recognition of cisplatin adducts by cellular proteins. Mutat Res. 2001;478(1- 2):1-21.
6. Vaisman A, Lim SE, Patrick SM, Copeland WC, Hinkle DC, Turchi JJ, et al. Effect of DNA polymerases and high mobility group protein 1 on the carrier ligand specificity for translesion synthesis past platinum-DNA adducts. Biochemistry. 1999;38(34):11026-39.
7. Siddik ZH. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene. 2003;22(47):7265-79.
8. Koberle B, Tomicic MT, Usanova S, Kaina B. Cisplatin resistance: preclinical findings and clinical implications. Biochim Biophys Acta. 2010;1806(2):172-82. Epub

9. Katano K, Kondo A, Safaei R, Holzer A, Samimi G, Mishima M, et al. Acquisition of resistance to cisplatin is accompanied by changes in the cellular pharmacology of copper. Cancer Res. 2002;62(22):6559-65.
10. Komatsu M, Sumizawa T, Mutoh M, Chen ZS, Terada K, Furukawa T, et al. Copper-transporting P-type adenosine triphosphatase (ATP7B) is associated with cisplatin resistance. Cancer Res. 2000;60(5):1312-6.
11. Katoh R, Takebayashi Y, Takenoshita S. Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) as a chemoresistance marker in human solid carcinomas. Ann Thorac Cardiovasc Surg. 2005;11(3):143-5. Epub 2005/07/21.
12. Ishikawa T, Ali-Osman F. Glutathione-associated cis- diamminedichloroplatinum(II) metabolism and ATP- dependent efflux from leukemia cells. Molecular characterization of glutathione-platinum complex and its biological significance. J Biol Chem. 1993;268(27):20116-25.
13. Byun SS, Kim SW, Choi H, Lee C, Lee E. Augmentation of cisplatin sensitivity in cisplatin- resistant human bladder cancer cells by modulating glutathione concentrations and glutathione-related enzyme activities. BJU Int. 2005;95(7):1086-90. Epub
14. Masters JR, Thomas R, Hall AG, Hogarth L, Matheson EC, Cattan AR, et al. Sensitivity of testis tumour cells to chemotherapeutic drugs: role of detoxifying pathways. Eur J Cancer. 1996;32A(7):1248-53. Epub 1996/06/01.
15. Surowiak P, Materna V, Kaplenko I, Spaczynski M, Dietel M, Lage H, et al. Augmented expression of metallothionein and glutathione S-transferase pi as unfavourable prognostic factors in cisplatin-treated ovarian cancer patients. Virchows Arch. 2005;447(3):626-33. Epub 2005/06/22.
16. Satoh T, Nishida M, Tsunoda H, Kubo T. Expression of glutathione S-transferase pi (GST-pi) in human malignant ovarian tumors. Eur J Obstet Gynecol Reprod Biol. 2001;96(2):202-8. Epub 2001/06/01.
17. Nishimura T, Newkirk K, Sessions RB, Andrews PA, Trock BJ, Rasmussen AA, et al. Immunohistochemical staining for glutathione S-transferase predicts response to platinum-based chemotherapy in head and neck cancer. Clin Cancer Res. 1996;2(11):1859-65. Epub 1996/11/01.
18. Goto S, Kamada K, Soh Y, Ihara Y, Kondo T.
19. Significance of nuclear glutathione S-transferase pi in resistance to anti-cancer drugs. Jpn J Cancer Res. 2002;93(9):1047-56. Epub 2002/10/03.
20. Ikeda K, Sakai K, Yamamoto R, Hareyama H, Tsumura N, Watari H, et al. Multivariate analysis for prognostic significance of histologic subtype, GST-pi, MDR-1, and p53 in stages II-IV ovarian cancer. Int J Gynecol Cancer. 2003;13(6):776-84. Epub 2003/12/17.
21. Miyatake K, Gemba K, Ueoka H, Nishii K, Kiura K, Tabata M, et al. Prognostic significance of mutant p53 protein, P-glycoprotein and glutathione S-transferase- pi in patients with unresectable non-small cell lung cancer. Anticancer Res. 2003;23(3C):2829-36. Epub
22. Koberle B, Masters JR, Hartley JA, Wood RD. Defective repair of cisplatin-induced DNA damage caused by reduced XPA protein in testicular germ cell tumours. Curr Biol. 1999;9(5):273-6. Epub 1999/03/13.
23. Ferry KV, Hamilton TC, Johnson SW. Increased nucleotide excision repair in cisplatin-resistant ovarian cancer cells: role of ERCC1-XPF. Biochem Pharmacol. 2000;60(9):1305-13. Epub 2000/09/29.
24. Rabik CA, Dolan ME. Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat Rev. 2007;33(1):9-23.
25. Li Q, Yu JJ, Mu C, Yunmbam MK, Slavsky D, Cross CL, et al. Association between the level of ERCC-1 expression and the repair of cisplatin-induced DNA damage in human ovarian cancer cells. Anticancer Res. 2000;20(2A):645-52.
26. Dabholkar M, Thornton K, Vionnet J, Bostick-Bruton F, Yu JJ, Reed E. Increased mRNA levels of xeroderma pigmentosum complementation group B (XPB) and Cockayne's syndrome complementation group B (CSB) without increased mRNA levels of multidrug-resistance gene (MDR1) or metallothionein-II (MT-II) in platinum- resistant human ovarian cancer tissues. Biochem Pharmacol. 2000;60(11):1611-9.
27. Metzger R, Leichman CG, Danenberg KD, Danenberg PV, Lenz HJ, Hayashi K, et al. ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy. J Clin Oncol. 1998;16(1):309-16.
28. Welsh C, Day R, McGurk C, Masters JR, Wood RD, Koberle B. Reduced levels of XPA, ERCC1 and XPF DNA repair proteins in testis tumor cell lines. Int J Cancer. 2004;110(3):352-61.
29. Martin SA, Lord CJ, Ashworth A. Therapeutic targeting of the DNA mismatch repair pathway. Clin Cancer Res. 2010;16(21):5107-13. Epub 2010/09/09.
30. Kunkel TA, Erie DA. DNA mismatch repair. Annu Rev Biochem. 2005;74:681-710. Epub 2005/06/15.
31. Karran P. Mechanisms of tolerance to DNA damaging therapeutic drugs. Carcinogenesis. 2001;22(12):1931-7. Epub 2001/12/26.
32. Kat A, Thilly WG, Fang WH, Longley MJ, Li GM, Modrich P. An alkylation-tolerant, mutator human cell line is deficient in strand-specific mismatch repair. Proc
33. Natl Acad Sci U S A. 1993;90(14):6424-8. Epub
34. Brown R, Hirst GL, Gallagher WM, McIlwrath AJ, Margison GP, van der Zee AG, et al. hMLH1 expression and cellular responses of ovarian tumour cells to treatment with cytotoxic anticancer agents. Oncogene. 1997;15(1):45-52.
35. Stojic L, Brun R, Jiricny J. Mismatch repair and DNA damage signalling. DNA Repair (Amst). 2004;3(8- 9):1091-101.
36. Durant ST, Morris MM, Illand M, McKay HJ, McCormick C, Hirst GL, et al. Dependence on RAD52 and RAD1 for anticancer drug resistance mediated by inactivation of mismatch repair genes. Curr Biol. 1999;9(1):51-4.
37. Kartalou M, Essigmann JM. Mechanisms of resistance to cisplatin. Mutat Res. 2001;478(1-2):23-43.
38. Samimi G, Fink D, Varki NM, Husain A, Hoskins WJ, Alberts DS, et al. Analysis of MLH1 and MSH2 expression in ovarian cancer before and after platinum drug-based chemotherapy. Clin Cancer Res. 2000;6(4):1415-21.
39. Shachar S, Ziv O, Avkin S, Adar S, Wittschieben J, Reissner T, et al. Two-polymerase mechanisms dictate error-free and error-prone translesion DNA synthesis in mammals. EMBO J. 2009;28(4):383-93. Epub
40. Ohashi E, Ogi T, Kusumoto R, Iwai S, Masutani C, Hanaoka F, et al. Error-prone bypass of certain DNA lesions by the human DNA polymerase kappa. Genes Dev. 2000;14(13):1589-94. Epub 2000/07/11.
41. Cruet-Hennequart S, Villalan S, Kaczmarczyk A, O'Meara E, Sokol AM, Carty MP. Characterization of the effects of cisplatin and carboplatin on cell cycle progression and DNA damage response activation in DNA polymerase eta-deficient human cells. Cell Cycle. 2009;8(18):3039-50. Epub 2009/08/29.
42. Albertella MR, Green CM, Lehmann AR, O'Connor MJ. A role for polymerase eta in the cellular tolerance to cisplatin-induced damage. Cancer Res. 2005;65(21):9799-806. Epub 2005/11/04.
43. Roos WP, Tsaalbi-Shtylik A, Tsaryk R, Guvercin F, de Wind N, Kaina B. The translesion polymerase Rev3L in the tolerance of alkylating anticancer drugs. Mol Pharmacol. 2009;76(4):927-34. Epub 2009/07/31.
44. Wang H, Zhang SY, Wang S, Lu J, Wu W, Weng L, et al. REV3L confers chemoresistance to cisplatin in human gliomas: the potential of its RNAi for synergistic therapy. Neuro Oncol. 2009;11(6):790-802. Epub 2009/03/18.
45. Wu F, Lin X, Okuda T, Howell SB. DNA polymerase zeta regulates cisplatin cytotoxicity, mutagenicity, and the rate of development of cisplatin resistance. Cancer Res. 2004;64(21):8029-35. Epub 2004/11/03.
46. Lin X, Trang J, Okuda T, Howell SB. DNA polymerase zeta accounts for the reduced cytotoxicity and
47. enhanced mutagenicity of cisplatin in human colon carcinoma cells that have lost DNA mismatch repair. Clin Cancer Res. 2006;12(2):563-8. Epub 2006/01/24.
48. Boudsocq F, Benaim P, Canitrot Y, Knibiehler M, Ausseil F, Capp JP, et al. Modulation of cellular response to cisplatin by a novel inhibitor of DNA polymerase beta. Mol Pharmacol. 2005;67(5):1485-92. Epub
49. Ceppi P, Novello S, Cambieri A, Longo M, Monica V, Lo Iacono M, et al. Polymerase eta mRNA expression predicts survival of non-small cell lung cancer patients treated with platinum-based chemotherapy. Clin Cancer Res. 2009;15(3):1039-45. Epub 2009/02/04.
50. Albertella MR, Lau A, O'Connor MJ. The overexpression of specialized DNA polymerases in cancer. DNA Repair (Amst). 2005;4(5):583-93. Epub 2005/04/07.
51. Pan Q, Fang Y, Xu Y, Zhang K, Hu X. Down-regulation of DNA polymerases kappa, eta, iota, and zeta in human lung, stomach, and colorectal cancers. Cancer Lett. 2005;217(2):139-47. Epub 2004/12/25.
52. Cetintas VB, Kucukaslan AS, Kosova B, Tetik A, Selvi N, Cok G, et al. Cisplatin resistance induced by decreased apoptotic activity in Non Small Cell Lung Cancer cell lines. Cell Biol Int. 2011. Epub 2011/10/11.
53. Branch P, Masson M, Aquilina G, Bignami M, Karran P. Spontaneous development of drug resistance: mismatch repair and p53 defects in resistance to cisplatin in human tumor cells. Oncogene. 2000;19(28):3138- 45. Epub 2000/08/02.
54. Xu GW, Mymryk JS, Cairncross JG. Inactivation of p53 sensitizes astrocytic glioma cells to BCNU and temozolomide, but not cisplatin. J Neurooncol. 2005;74(2):141-9. Epub 2005/09/30.
55. Gadducci A, Cosio S, Muraca S, Genazzani AR. Molecular mechanisms of apoptosis and chemosensitivity to platinum and paclitaxel in ovarian cancer: biological data and clinical implications. Eur J Gynaecol Oncol. 2002;23(5):390-6. Epub 2002/11/21.
56. Sakakura C, Sweeney EA, Shirahama T, Igarashi Y, Hakomori S, Tsujimoto H, et al. Overexpression of bax sensitizes breast cancer MCF-7 cells to cisplatin and etoposide. Surg Today. 1997;27(7):676-9.
57. Sugimoto C, Fujieda S, Seki M, Sunaga H, Fan GK, Tsuzuki H, et al. Apoptosis-promoting gene (bax) transfer potentiates sensitivity of squamous cell carcinoma to cisplatin in vitro and in vivo. Int J Cancer. 1999;82(6):860-7.
58. Taylor JK, Zhang QQ, Monia BP, Marcusson EG, Dean NM. Inhibition of Bcl-xL expression sensitizes normal human keratinocytes and epithelial cells to apoptotic stimuli. Oncogene. 1999;18(31):4495-504.
59. Chresta CM, Masters JR, Hickman JA. Hypersensitivity of human testicular tumors to etoposide-induced apoptosis is associated with functional p53 and a high Bax:Bcl-2 ratio. Cancer Res. 1996;56(8):18