JS-K逆转由GST介导的耐顺铂人肺腺癌细胞（A549/DDP）耐药性的研究
摘要
目的：1、研究JS-K对耐顺铂人肺腺癌细胞A549／DDP耐药的逆转作用。2、研究JS-K对人肺腺癌细胞A549及耐顺铂人肺腺癌细胞A549／DDP多药耐药相关基因GST-πmRNA表达的影响。方法：1、采用MTT法检测JS-K联合顺铂对耐顺铂人肺腺癌细胞A549/DDP的抑制作用及逆转倍数。2、采用real-time RT-PCI法检测不同浓度JS-K处理前后人肺腺癌细胞A549及耐顺铂人肺腺癌细胞A549／DDP的GST-πmRNA的表达。结果：1、顺铂对人肺腺癌细胞A549及耐顺铂人肺腺癌细胞A549／DDP(48h)的IC50值分别为1.702±0.100μg/ml、9.943±0.063μg/ml,其抑制作用差异有统计学意义(P<0.05)；JS-K对人肺腺癌细胞A549及耐顺铂人肺腺癌细胞A549／DDP均有抑制作用,其抑制作用差异无统计学意义(P>0.05)。JS-K对耐顺铂人肺腺癌细胞A549／DDP的IC10值为1.042±0.124μM。以JS-K IC10值以下的浓度为无毒剂量,选择0.1μM、0.3μM、1μM三种不同浓度的JS-K联合顺铂可以增加耐顺铂人肺腺癌细胞A549／DDP对顺铂的敏感性,使顺铂的IC50值分别降至1.963±0.238μg/ml.1.371±0.119μg/ml、1.083±0.055μg/ml,差异有统计学意义(P<0.05)。对顺铂的耐药逆转倍数分别为5.066、7.254、9.178。2.0.1μgM、0.3μM、1μM三种不同浓度的JS-K处理两种细胞48h后检测其耐药基因GST-πmRNA表达,其GST-πmRNA的相对表达量均较对照组明显下降,且呈浓度依赖性,差异有统计学意义(P<0.05)。结论：JS-K可以增强耐顺铂人肺腺癌细胞A549/DDP对顺铂的敏感性,逆转其耐药。这可能与下调多药耐药相关基因GST-πmRNA表达有关。
Objective:To investigate the reversal effects of the nitric oxide (NO) prodrug JS-K on GST-induced cisplatin resistant cell line A549/DDP. To investigate the impact of JS-K to the expression of GST-πmRNA on A549/DDP and A549 cells. Methods:A549 and A549 /DDP cells were cultured with DDP alone or in combination with JS-K respectively. The inhibition of DDP and the inhibition of DDP in combination with JS-K were assessed with MTT and the IC50 values were calculated. The expression of GST-πmRNA was detected by real-time quantitative reverse transcription-polymerase chain reaction (real-time RT-PCR). Results:The IC 50 value was 1.702±0.100μg/ml,9.943±0.063μg/ml when A549 and A549/DDP cells treated with DDP. The difference between the two groups had no statistical significance (P<0.05). JS-K also has an inhibition effect on both A549 and A549/DDP cells. The difference between the two groups had no statistical significance (P> 0.05).The JS-K IC 10 value was 1.042±0.124μM. Chose JS-K IC10 value as its non-toxic dose. DDP combined with JS-K (0.1μM,0.3μM, 1μM) that bellowed its IC 10 value could significant decrease the IC50 value to 1.963±0.238μg/ml,1.371±0.119μg/ml, 1.083±0.055μg/ml in a concentration dependent manner on A549/DDP cells. The difference compared with blank had statistical significance (P<0.05). The reversal fold was 5.066,7.254,9.178. The GST-πmRNA expression was down regulated after JS-K (0.1μM,0.3μM, 1μM) treated 48h. It induced concentration dependent GST-πmRNA expression changes on A549 and A549/DDP cells. The difference compared with blank had statistical significance (P< 0.05). Conclusion:JS-K can enhance the sensitivity of A549/DDP cells to cisplatin. The reversal effect may be relevant to the down regulation of GST-πmRNA expressions.
Objective:To investigate the reversal effects of the nitric oxide (NO) prodrug JS-K on GST-induced cisplatin resistant cell line A549/DDP. To investigate the impact of JS-K to the expression of GST-πmRNA on A549/DDP and A549 cells. Methods:A549 and A549 /DDP cells were cultured with DDP alone or in combination with JS-K respectively. The inhibition of DDP and the inhibition of DDP in combination with JS-K were assessed with MTT and the IC50 values were calculated. The expression of GST-πmRNA was detected by real-time quantitative reverse transcription-polymerase chain reaction (real-time RT-PCR). Results:The IC 50 value was 1.702±0.100μg/ml,9.943±0.063μg/ml when A549 and A549/DDP cells treated with DDP. The difference between the two groups had no statistical significance (P<0.05). JS-K also has an inhibition effect on both A549 and A549/DDP cells. The difference between the two groups had no statistical significance (P> 0.05).The JS-K IC 10 value was 1.042±0.124μM. Chose JS-K IC10 value as its non-toxic dose. DDP combined with JS-K (0.1μM,0.3μM, 1μM) that bellowed its IC 10 value could significant decrease the IC50 value to 1.963±0.238μg/ml,1.371±0.119μg/ml, 1.083±0.055μg/ml in a concentration dependent manner on A549/DDP cells. The difference compared with blank had statistical significance (P<0.05). The reversal fold was 5.066,7.254,9.178. The GST-πmRNA expression was down regulated after JS-K (0.1μM,0.3μM, 1μM) treated 48h. It induced concentration dependent GST-πmRNA expression changes on A549 and A549/DDP cells. The difference compared with blank had statistical significance (P< 0.05). Conclusion:JS-K can enhance the sensitivity of A549/DDP cells to cisplatin. The reversal effect may be relevant to the down regulation of GST-πmRNA expressions.
引文
1. Noble J. Second-line or Subsequent systemic therapy for recurrent or progressive non-lung cancer:a systematic review and practice guideline. Journal of Thoracic Oncology,2006,1:1042-1058.
2. Levi F, Lucchini F, Negri E, et al. Cancer mortality in Europe,1995-1999, and an overview of trends since 1960. Int J Cancer,2004,110:155-69.
3. Seve P, Dumontet C. Chemoresistance in non-small cell lung cancer. Curr Med Chem Anticancer Agents,2005,5:73-88.
4. Lang DS, Droemann D, Schultz H, et al. A novel human ex vivo model for the analysis of molecular events during lung cancer chemotherapy. Respir Res,2007,8: 43.
5. Daruka M, Alan F. Targeting the multidrug resistance-1 transporter in AML: molecular regulation and therapeutic strategies. Blood,2004,104 (7):1940-1951.
6. Roy S, Kenny E, Kennedy S, et al. MDR1/P-glycoprotein and MRP-1 mRNA and protein expression in non-small cell lung cancer. Anticancer Res,2007,27 (3A): 1325-1330.
7. Borst P, Evers R, Kool M, et al. A family of drug transporters:the multidrug resistance-associated proteins. Natl Cancer Inst,2000,92 (16):1295-1302.
8. Oguri T, Ozasa H, Uemura T, et al. MRP7/ABCC10 expression is a predictive biomarker for the resistance to paclitaxel in non-small cell lung cancer. Mol Cancer Ther,2008,7 (5):1150-1155.
9. Juranka PF, Zastawny RL, Ling V. P-glycoprotein:multidrug-resistance and a superfamily of membrane-associated transport proteins. FASEB J,1989; 3: 2583-2592.
10. Zhou SF, Wang LL, Di YM, et al. Substrates and inhibitors of human multidrug resistance associated proteins and the implications in drug development. Curr Med Chem,2008,15 (20):1981-2039.
11. Saavedra JE, Srinivasan A, Bonifant CL, et al. The secondary amine/nitric oxide complex ion R.2N[N(O)NO]- as nucleophile and leaving group in SNAr reactions. OrgChem,2001,66:3090-8.
12. Keefer LK. Nitric oxide-releasing compounds:from basic research to promising drug. Mod Drug Discov,1998,Ⅰ (2):20-30.
13. Shami PH, Saacedra JE, Wang LY, et al. JS-K, a glutathione/glutathione S-transferase-activated nitric oxide donor of the diazeniumdiolate class with potent antineopalstic activity. Mol Cancer Ther,2003,2(4):409-417.
14. Ren Z, Kar S, Wang Z, Wang M, Saaredra JE, Carr BI. JS-K, a novel non-ionic diazeniumdiolate derivative, inhibits Hep 3B hepatoma cell growth and induces c-Jun phosphorylation via multiple MAP kinase pathways. Cell Physiol 2003; 197:426-34.
15.蔡鹏、刘叙仪、韩复生.耐顺铂人肺腺癌细胞系A549／DDP的建立及耐药机制.中国肿瘤临床,1995,22(8)：582-587.
16. Ikuta K, Takemura Khara. Defects in apoptoic signal transduction in cisplatin-resistiant non-small cell lung cancer cells. Oncol Rep,2005,13:1229-1234.
17. Bai F, Nakanishi Y, Kawasaki M, et al. Immunohistochemical expression of glutathione S-transferase-Pi can predict chemotherapy response in patients with non-small-cell lung carcinoma. Cancer,1996,78 (3):416-421
18. Adler V, Yin Z M, Fuchs S Y, et al. Regulation of JNK signaling by GST-pi. EMOB. J,1999,18 (5):1321-1334.
19. T. Kiziltepe, et al, JS-K, a GST-activated nitric oxide generator, induces DNA double-strand breaks, activates DNA damage response pathways, and induces apoptosis in vitro and in vivo in human multiple myeloma cells. Blood,2007,110: 709-718.
20. Liu J, Li C, Qu W, et al. Nitric oxide prodrugs and metallochemotherapeutics:JS-K and CB-3-100 enhance arsenic and cisplatin cytolethality by increasing cellular accumulation. Mol Cancer Ther,2004,3 (6):709-14.
1. Wang AL, Few KD. Increased glutathione-S-transferase activity in a cell line with acquired resistance to nitrogen mustards. Cancer Treat Rep,1985,69 (5):677-682.
2. Oakley AJ, Lo BeHo M, Nucceteili M, et al. The ligandin (non-substrate) binding site of human pi class glutathione transferase is located in the electrophile binding site (H-site). J Mol Biol,1999,291 (4):913-926.
3. Tew KD. Redox in redux:Emergent roles for glutathione S-transferase P (GSTP) in regulation of cell signaling and S-glutathionylation. Biochem Pharmacol,2007,73 (9): 1257-1269.
4. Goto S, Ihara Y, Urata Y, et al. Doxorubicin-induced DNA intercalation and scavenging by nuclear glutathione-S-transferase π. FASEB J,2001,15 (14) 2702-2714.
5. Benlloch M, Ortega A, Ferrer P, et al. Acceleration of glutathione efflux and inhibition of gamma-glutamyltranspeptidase sensitize metastatic B16 melanoma cells to endothelium-induced cytotoxicity. J Biol Chem,2005,280 (8):6950-6959.
6. Gurbuxani S, Zhou D, Simonin G, et al. Expression of genes implicated in multidrug resistance in acute lymphoblastic leukemia in India. Ann Hematol,1998,76 (5) 195-200.
7. Den Boer M L, Pieters R, Kazemier K M, et al. Different expression of glutathione-S-transferase alpha, mu and pi in childhood acute lymphoblastic and myeloid leukaemia. Br J Haematol,1999,104 (2):321-327.
8. Ascione A, Cianfriglia M, et al. The glutathione S-transferase inhibitor 6-(7-nitro-2,1, 3-benzoxadiazol-4-ylthio) hexanol overcomes the MDR1-P-glycoprotein and MRP1-mediated multidrug resistance in acute myeloid leukemia cells. Cancer Chemother Pharmacol,2009,64 (2):419-424.
9. Cullen KJ, Newkirk KA, Schumaker LM, et al. Glutathione S-transferase pi amplification is associated with cisplatin resistance in head and neck squamous cell carcinoma cell lines and primary tumors. Cancer Res,2003,63 (23):8097-8102.
10. Procopio A, Alcaro S, Cundari S. et al. Molecular modeling, synthesis, and preliminary biological evaluation of glutathione-S-transferase inhibitors as potential therapeutic agents. J Med Chem,2005,48 (19):6084-6089
11. Enokida H, Shiina H, Urakami S, et al. Multigene methylation analysis for detection and staging of prostate cancer. Clin Cancer Res,2005,11 (18):6582-6588
12. Gurbuxani S, Raina V, et al. Significance of MDR1, MRP 1, GST pi and GST mu mRNA expression in acute lymphoblastic leukemia in Indian patients. Cancer Lett, 2001,167 (1):73-83.
13. Autrup J L, Hokland P, Pedersen L, et al. Effect of glutathione S-transferases on the survival of patients with acute myeloid leukaemia. Eur J Pharmacol,2002,438 (1-2): 15-18.
14. Wu Z, Minhas GS, Wen D, et al. Design, synthesis, and structure-activity relationships of haloenollactones:site-directed and isozyme-selective glutathione S-transferase inhibitors. Med Chem,2004,47 (12):3282-3294.
15. Ricci G, De Maria F, Antonini G, et al.7-Nitro-2,1,3-benzoxadiazole derivatives, a new class of suicide inhibitors for glutathione S-transferases. Mechanism of action of potential anticancer drugs. J Biol Chem,2005,280 (28):26397-26405.
16. Turella P, Cerella C, Filomeni G, et al. Proapoptotic activity of new glutathione S-transferase inhibitors. Cancer Res,2005,65 (9):3751-3761.
17. Ang, WH, Parker LJ, De Luca A, et al. Rational design of an organometallic glutathione transferase inhibitor. Angew Chem Int Ed Engl,2009,48 (21):3854-3857.
18. Mahajan, S, Atkins WM. The chemistry and biology of inhibitors and pro-drugs targeted to glutathione S-transferases. Cell Mol Life Sci,2005,62 (11):1221-1233.
19. Burg D, Riepsaame J, Pont C, et al. Peptide-bond modified glutathione conjugate analogs modulate GSTpi function in GSH-conjugation, drug sensitivity and JNK signaling. Biochem Pharmacol,2006,71 (3):268-277
20. Townsend DM, Tew KD. The role of glutathione-s-transferase in anti-cancer drug resistance. Oncogene,2003,22 (47):7369-7375.
21. Caffrey PB, Zhu M, Zhang Y, et al. Rapid development of glutathione S-transferase dependent drug resistance in vitro and its prevention by ethacrynic acid. Cancer Lett, 1999,136 (1):472 52.
22. Flatgaard JE, Bauer KE, Kauvarl LM. Isozyme specificity of novel glutathione-S-tranferase inhibitors. Cancer Chemother Pharmacol,1993,33 (1):63-70.
23. Burg D, Filippov DV, Hermanns R, et al. Peptidomimetic glutathione analogues as novel gammaGT stable GST inhibitors. Bioorg Med Chem,2002,10 (1):195-205.
24. Kim SJ, Kim MS, Lee JW, et al. Dihydroartemisinin enhances radiosensitivity of human glioma cells in vitro. J Cancer Res Clin Oncol,2006,132 (2):129-135.
25. Mukanganyama S, Widersten M, Naik YS, et al. Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. Int J Cancer,2002,97 (5):700-705.
26. van Haaften RI, Haenen GR, et al. Inhibition of various glutathione S-transferase isoenzymes by RRR-alpha-tocopherol. Toxicol in Vitro,2003,17 (3):245-251
27. van Haaften RI, Evelo CT, Haenen GR, et al. alpha-Tocopherol inhibits human glutathione S-transferase pi. Biochem Biophysi Res Commun,2001,280 (3):631-633.
28. Yu ST, Chen TM, Chern JW, Tseng SY, Chen YH. Downregulation of GSTpi expression by tryptanthrin contributing to sensitization of doxorubicin-resistant MCF-7 cells through c-jun NH2-terminal kinase-mediated apoptosis. Anticancer Drugs,2009, 20 (5):382-388.
29. Hayeshi R, Mutingwende I, Mavengere W, Masiyanise V, Mukanganyama S, et al.The inhibition of human glutathione S-transferases activity by plant polyphenolic compounds ellagic acid and curcumin. Food Chem Toxicol,2007,45 (2):286-295.
30. Azra Raza, Naomi Galili, Natalie Callander, et al. Phase 1-2a multicenter dose-escalation study of ezatiostat hydrochloride liposomes for injection (Telintra, TLK199), a novel glutathione analog prodrug in patients with myelodysplastic syndrome. J Hematol Oncol,2009,2:20.
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33. Shami PJ, Saavedra JA, Wang LY, et al. JS-K, a glutathione/glutathione S-transferase activated nitric oxide donor of the diazeniumdiolate class with potent antineoplastic activity. Mol Cancer Ther,2003,2 (4):409-417.
34. Ren Z, Kar S, Wang Z, et al. JS-K, a novel non-ionic diazeniumdiolate derivative, inhibits Hep 3B hepatoma cell growth and induces c-Jun phosphorylation via multiple MAP kinase pathways. J Cell Physiol,2003,197 (3):426-34.
35. Udupi V, Yu M, Malaviya S, Saavedra JE, Shami PJ. JS-K, a nitric oxide prodrug, induces cytochrome c release and caspase activation in HL-60 myeloid leukemia cells. Leuk Res,2006,30 (10):1279-1283.
36. Simeone AM, McMurtry V, Nieves-Alicea R, et al. TIMP-2 mediates the anti-invasive effects of the nitric oxide-releasing prodrug JS-K in breast cancer cells. Breast Cancer Res,2008,10(3).
37. Liu J, Li C, Qu W, et al. Nitric oxide p rodrugs and metallochemotherapeutics:JS-K and CB-3-100 enhance arsenic and cisplatin cytolethality by increasing cellular accumulation. Mol Cancer Ther,2004,3 (6):709-714.
38. T. Kiziltepe, et al. JS-K, a GST-activated nitric oxide generator, induces DNA double-strand breaks, activates DNA damage response pathways, and induces apoptosis in vitro and in vivo in human multiple myeloma cells. Blood,2007,110: 709-718.
2. Levi F, Lucchini F, Negri E, et al. Cancer mortality in Europe,1995-1999, and an overview of trends since 1960. Int J Cancer,2004,110:155-69.
3. Seve P, Dumontet C. Chemoresistance in non-small cell lung cancer. Curr Med Chem Anticancer Agents,2005,5:73-88.
4. Lang DS, Droemann D, Schultz H, et al. A novel human ex vivo model for the analysis of molecular events during lung cancer chemotherapy. Respir Res,2007,8: 43.
5. Daruka M, Alan F. Targeting the multidrug resistance-1 transporter in AML: molecular regulation and therapeutic strategies. Blood,2004,104 (7):1940-1951.
6. Roy S, Kenny E, Kennedy S, et al. MDR1/P-glycoprotein and MRP-1 mRNA and protein expression in non-small cell lung cancer. Anticancer Res,2007,27 (3A): 1325-1330.
7. Borst P, Evers R, Kool M, et al. A family of drug transporters:the multidrug resistance-associated proteins. Natl Cancer Inst,2000,92 (16):1295-1302.
8. Oguri T, Ozasa H, Uemura T, et al. MRP7/ABCC10 expression is a predictive biomarker for the resistance to paclitaxel in non-small cell lung cancer. Mol Cancer Ther,2008,7 (5):1150-1155.
9. Juranka PF, Zastawny RL, Ling V. P-glycoprotein:multidrug-resistance and a superfamily of membrane-associated transport proteins. FASEB J,1989; 3: 2583-2592.
10. Zhou SF, Wang LL, Di YM, et al. Substrates and inhibitors of human multidrug resistance associated proteins and the implications in drug development. Curr Med Chem,2008,15 (20):1981-2039.
11. Saavedra JE, Srinivasan A, Bonifant CL, et al. The secondary amine/nitric oxide complex ion R.2N[N(O)NO]- as nucleophile and leaving group in SNAr reactions. OrgChem,2001,66:3090-8.
12. Keefer LK. Nitric oxide-releasing compounds:from basic research to promising drug. Mod Drug Discov,1998,Ⅰ (2):20-30.
13. Shami PH, Saacedra JE, Wang LY, et al. JS-K, a glutathione/glutathione S-transferase-activated nitric oxide donor of the diazeniumdiolate class with potent antineopalstic activity. Mol Cancer Ther,2003,2(4):409-417.
14. Ren Z, Kar S, Wang Z, Wang M, Saaredra JE, Carr BI. JS-K, a novel non-ionic diazeniumdiolate derivative, inhibits Hep 3B hepatoma cell growth and induces c-Jun phosphorylation via multiple MAP kinase pathways. Cell Physiol 2003; 197:426-34.
15.蔡鹏、刘叙仪、韩复生.耐顺铂人肺腺癌细胞系A549／DDP的建立及耐药机制.中国肿瘤临床,1995,22(8)：582-587.
16. Ikuta K, Takemura Khara. Defects in apoptoic signal transduction in cisplatin-resistiant non-small cell lung cancer cells. Oncol Rep,2005,13:1229-1234.
17. Bai F, Nakanishi Y, Kawasaki M, et al. Immunohistochemical expression of glutathione S-transferase-Pi can predict chemotherapy response in patients with non-small-cell lung carcinoma. Cancer,1996,78 (3):416-421
18. Adler V, Yin Z M, Fuchs S Y, et al. Regulation of JNK signaling by GST-pi. EMOB. J,1999,18 (5):1321-1334.
19. T. Kiziltepe, et al, JS-K, a GST-activated nitric oxide generator, induces DNA double-strand breaks, activates DNA damage response pathways, and induces apoptosis in vitro and in vivo in human multiple myeloma cells. Blood,2007,110: 709-718.
20. Liu J, Li C, Qu W, et al. Nitric oxide prodrugs and metallochemotherapeutics:JS-K and CB-3-100 enhance arsenic and cisplatin cytolethality by increasing cellular accumulation. Mol Cancer Ther,2004,3 (6):709-14.
1. Wang AL, Few KD. Increased glutathione-S-transferase activity in a cell line with acquired resistance to nitrogen mustards. Cancer Treat Rep,1985,69 (5):677-682.
2. Oakley AJ, Lo BeHo M, Nucceteili M, et al. The ligandin (non-substrate) binding site of human pi class glutathione transferase is located in the electrophile binding site (H-site). J Mol Biol,1999,291 (4):913-926.
3. Tew KD. Redox in redux:Emergent roles for glutathione S-transferase P (GSTP) in regulation of cell signaling and S-glutathionylation. Biochem Pharmacol,2007,73 (9): 1257-1269.
4. Goto S, Ihara Y, Urata Y, et al. Doxorubicin-induced DNA intercalation and scavenging by nuclear glutathione-S-transferase π. FASEB J,2001,15 (14) 2702-2714.
5. Benlloch M, Ortega A, Ferrer P, et al. Acceleration of glutathione efflux and inhibition of gamma-glutamyltranspeptidase sensitize metastatic B16 melanoma cells to endothelium-induced cytotoxicity. J Biol Chem,2005,280 (8):6950-6959.
6. Gurbuxani S, Zhou D, Simonin G, et al. Expression of genes implicated in multidrug resistance in acute lymphoblastic leukemia in India. Ann Hematol,1998,76 (5) 195-200.
7. Den Boer M L, Pieters R, Kazemier K M, et al. Different expression of glutathione-S-transferase alpha, mu and pi in childhood acute lymphoblastic and myeloid leukaemia. Br J Haematol,1999,104 (2):321-327.
8. Ascione A, Cianfriglia M, et al. The glutathione S-transferase inhibitor 6-(7-nitro-2,1, 3-benzoxadiazol-4-ylthio) hexanol overcomes the MDR1-P-glycoprotein and MRP1-mediated multidrug resistance in acute myeloid leukemia cells. Cancer Chemother Pharmacol,2009,64 (2):419-424.
9. Cullen KJ, Newkirk KA, Schumaker LM, et al. Glutathione S-transferase pi amplification is associated with cisplatin resistance in head and neck squamous cell carcinoma cell lines and primary tumors. Cancer Res,2003,63 (23):8097-8102.
10. Procopio A, Alcaro S, Cundari S. et al. Molecular modeling, synthesis, and preliminary biological evaluation of glutathione-S-transferase inhibitors as potential therapeutic agents. J Med Chem,2005,48 (19):6084-6089
11. Enokida H, Shiina H, Urakami S, et al. Multigene methylation analysis for detection and staging of prostate cancer. Clin Cancer Res,2005,11 (18):6582-6588
12. Gurbuxani S, Raina V, et al. Significance of MDR1, MRP 1, GST pi and GST mu mRNA expression in acute lymphoblastic leukemia in Indian patients. Cancer Lett, 2001,167 (1):73-83.
13. Autrup J L, Hokland P, Pedersen L, et al. Effect of glutathione S-transferases on the survival of patients with acute myeloid leukaemia. Eur J Pharmacol,2002,438 (1-2): 15-18.
14. Wu Z, Minhas GS, Wen D, et al. Design, synthesis, and structure-activity relationships of haloenollactones:site-directed and isozyme-selective glutathione S-transferase inhibitors. Med Chem,2004,47 (12):3282-3294.
15. Ricci G, De Maria F, Antonini G, et al.7-Nitro-2,1,3-benzoxadiazole derivatives, a new class of suicide inhibitors for glutathione S-transferases. Mechanism of action of potential anticancer drugs. J Biol Chem,2005,280 (28):26397-26405.
16. Turella P, Cerella C, Filomeni G, et al. Proapoptotic activity of new glutathione S-transferase inhibitors. Cancer Res,2005,65 (9):3751-3761.
17. Ang, WH, Parker LJ, De Luca A, et al. Rational design of an organometallic glutathione transferase inhibitor. Angew Chem Int Ed Engl,2009,48 (21):3854-3857.
18. Mahajan, S, Atkins WM. The chemistry and biology of inhibitors and pro-drugs targeted to glutathione S-transferases. Cell Mol Life Sci,2005,62 (11):1221-1233.
19. Burg D, Riepsaame J, Pont C, et al. Peptide-bond modified glutathione conjugate analogs modulate GSTpi function in GSH-conjugation, drug sensitivity and JNK signaling. Biochem Pharmacol,2006,71 (3):268-277
20. Townsend DM, Tew KD. The role of glutathione-s-transferase in anti-cancer drug resistance. Oncogene,2003,22 (47):7369-7375.
21. Caffrey PB, Zhu M, Zhang Y, et al. Rapid development of glutathione S-transferase dependent drug resistance in vitro and its prevention by ethacrynic acid. Cancer Lett, 1999,136 (1):472 52.
22. Flatgaard JE, Bauer KE, Kauvarl LM. Isozyme specificity of novel glutathione-S-tranferase inhibitors. Cancer Chemother Pharmacol,1993,33 (1):63-70.
23. Burg D, Filippov DV, Hermanns R, et al. Peptidomimetic glutathione analogues as novel gammaGT stable GST inhibitors. Bioorg Med Chem,2002,10 (1):195-205.
24. Kim SJ, Kim MS, Lee JW, et al. Dihydroartemisinin enhances radiosensitivity of human glioma cells in vitro. J Cancer Res Clin Oncol,2006,132 (2):129-135.
25. Mukanganyama S, Widersten M, Naik YS, et al. Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. Int J Cancer,2002,97 (5):700-705.
26. van Haaften RI, Haenen GR, et al. Inhibition of various glutathione S-transferase isoenzymes by RRR-alpha-tocopherol. Toxicol in Vitro,2003,17 (3):245-251
27. van Haaften RI, Evelo CT, Haenen GR, et al. alpha-Tocopherol inhibits human glutathione S-transferase pi. Biochem Biophysi Res Commun,2001,280 (3):631-633.
28. Yu ST, Chen TM, Chern JW, Tseng SY, Chen YH. Downregulation of GSTpi expression by tryptanthrin contributing to sensitization of doxorubicin-resistant MCF-7 cells through c-jun NH2-terminal kinase-mediated apoptosis. Anticancer Drugs,2009, 20 (5):382-388.
29. Hayeshi R, Mutingwende I, Mavengere W, Masiyanise V, Mukanganyama S, et al.The inhibition of human glutathione S-transferases activity by plant polyphenolic compounds ellagic acid and curcumin. Food Chem Toxicol,2007,45 (2):286-295.
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