Cancer Letters
Volume 291, Issue 2 , Pages 200-208 , 28 May 2010

Triptolide simultaneously induces reactive oxygen species, inhibits NF-κB activity and sensitizes 5-fluorouracil in colorectal cancer cell lines

  • Bing Xu

      Affiliations

    • Research Institute in Healthcare Science, School of Applied Sciences, University of Wolverhampton, Wolverhampton WV1 1SB, UK
    • Nanfang Hospital, The Southern Medical University, Guangzhou, PR China
    • Visiting fellow from Nanfang Hospital, The Southern Medical University, Guangzhou, PR China.
    • Equally contributed to this work.
    • ,
  • Xiaoxia Guo

      Affiliations

    • Research Institute in Healthcare Science, School of Applied Sciences, University of Wolverhampton, Wolverhampton WV1 1SB, UK
    • Equally contributed to this work.
    • ,
  • Sumi Mathew

      Affiliations

    • Research Institute in Healthcare Science, School of Applied Sciences, University of Wolverhampton, Wolverhampton WV1 1SB, UK
    • ,
  • Angel L Armesilla

      Affiliations

    • Research Institute in Healthcare Science, School of Applied Sciences, University of Wolverhampton, Wolverhampton WV1 1SB, UK
    • ,
  • James Cassidy

      Affiliations

    • Centre for Oncology and Applied Pharmacology, University of Glasgow, Glasgow, UK
    • ,
  • John L Darling

      Affiliations

    • Research Institute in Healthcare Science, School of Applied Sciences, University of Wolverhampton, Wolverhampton WV1 1SB, UK
    • ,
  • Weiguang Wang

      Affiliations

    • Research Institute in Healthcare Science, School of Applied Sciences, University of Wolverhampton, Wolverhampton WV1 1SB, UK
    • Corresponding Author InformationCorresponding author. Tel.: +44 1902 322756; fax: +44 1902 322714.

Received 14 August 2009 ,Revised 14 October 2009 ,Accepted 15 October 2009.

References 

  1. Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat. Rev. Cancer. 2003;3:330–338
  2. Sobrero A, Kerr D, Glimelius B, Van Cutsem E, Milano G, Pritchard DM, et al. New directions in the treatment of colorectal cancer: a look to the future. Eur. J. Cancer. 2000;36:559–566
  3. Limtrakul P. Curcumin as chemosensitizer. Adv. Exp. Med. Biol. 2007;595:269–300
  4. Pelicano H, Carney D, Huang P. ROS stress in cancer cells and therapeutic implications. Drug Resist Update. 2004;7:97–110
  5. Yamamoto Y, Gaynor RB. Role of the NF-kappaB pathway in the pathogenesis of human disease states. Curr. Mol. Med. 2001;1:287–296
  6. Rayet B, Gelinas C. Aberrant rel/nfkb genes and activity in human cancer. Oncogene. 1999;18:6938–6947
  7. Wang CY, Mayo MW, Korneluk RG, Goeddel DV, Baldwin AS. NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science. 1998;281:1680–1683
  8. Wu MX, Ao Z, Prasad KV, Wu R, Schlossman SF. IEX-1L, an apoptosis inhibitor involved in NF-kappaB-mediated cell survival. Science. 1998;281:998–1001
  9. Wang CY, Guttridge DC, Mayo MW, Baldwin AS. NF-kappaB induces expression of the Bcl-2 homologue A1/Bfl-1 to preferentially suppress chemotherapy-induced apoptosis. Mol. Cell. Biol. 1999;19:5923–5929
  10. Wang W, Cassidy J, O’brien V, Ryan KM, Collie-Duguid E. Mechanistic and predictive profiling of 5-Fluorouracil resistance in human cancer cells. Cancer Res. 2004;64:8167–8176
  11. Wang CY, Cusack JC, Liu R, Baldwin AS. Control of inducible chemoresistance. enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kappaB. Nat. Med. 1999;5:412–417
  12. Wang CY, Mayo MW, Baldwin AS. TNF – and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kappaB. Science. 1996;274:784–787
  13. Cusack JC, Liu R, Houston M, Abendroth K, Elliott PJ, Adams J, et al. Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: implications for systemic nuclear factor-kappaB inhibition. Cancer Res. 2001;61:3535–3540
  14. Wang W, Cassidy J. Constitutive nuclear factor-kappaB mRNA, Protein overexpression and enhanced DNA-binding activity in thymidylate synthase inhibitor-resistant tumour cells. Br. J. Cancer. 2003;88:624–629
  15. Brinker AM, Ma J, Lipsky PE, Raskin I. Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae). Phytochemistry. 2007;68:732–766
  16. Carter BZ, Mak DH, Schober WD, Mcqueen T, Harris D, Estrov Z, et al. Triptolide induces caspase-dependent cell death mediated via the mitochondrial pathway in leukemic cells. Blood. 2006;108:630–637
  17. Tengchaisri T, Chawengkirttikul R, Rachaphaew N, Reutrakul V, Sangsuwan R, Sirisinha S. Antitumor activity of triptolide against cholangiocarcinoma growth in vitro and in hamsters. Cancer Lett. 1998;133:169–175
  18. Shamon LA, Pezzuto JM, Graves JM, Mehta RR, Wangcharoentrakul S, Sangsuwan R, et al. Evaluation of the mutagenic, cytotoxic, and antitumor potential of triptolide, a highly oxygenated diterpene isolated from Tripterygium wilfordii. Cancer Lett. 1997;112:113–117
  19. Lu LH, Lian YY, He GY, Lin SP, Huan SH, Chen ZZ, et al. Clinical study of triptolide treatment of acute leukemia. Clin. Exp. Investig. Hematol. 1992;3:1–3
  20. Lee KY, Chang W, Qiu D, Kao PN, Rosen GD. PG490 (triptolide) cooperates with tumor necrosis factor-alpha to induce apoptosis in tumor cells. J. Biol. Chem. 1999;274:13451–13455
  21. Tang XY, Zhu YQ, Tao WH, Wei B, Lin XL. Synergistic effect of triptolide combined with 5-fluorouracil on colon carcinoma. Postgrad. Med. J. 2007;83:338–343
  22. Chang WT, Kang JJ, Lee KY, Wei K, Anderson E, Gotmare S, et al. Triptolide and chemotherapy cooperate in tumor cell apoptosis. A role for the p53 pathway. J. Biol. Chem. 2001;276:2221–2227
  23. Choi YJ, Kim TG, Kim YH, Lee SH, Kwon YK, Suh SI, et al. Immunosuppressant PG490 (triptolide) induces apoptosis through the activation of caspase-3 and down-regulation of XIAP in U937 cells. Biochem. Pharmacol. 2003;66:273–280
  24. Wan CK, Wang C, Cheung HY, Yang M, Fong WF. Triptolide induces Bcl-2 cleavage and mitochondria dependent apoptosis in p53-deficient HL-60 cells. Cancer Lett. 2006;241:31–41
  25. Qiu D, Zhao G, Aoki Y, Shi L, Uyei A, Nazarian S, et al. Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-kappaB transcriptional activation. J. Biol. Chem. 1999;274:13443–13450
  26. Jiang XH, Wong BC, Lin MC, Zhu GH, Kung HF, Jiang SH, et al. Functional p53 is required for triptolide-induced apoptosis and AP-1 and nuclear factor-kappaB activation in gastric cancer cells. Oncogene. 2001;20:8009–8018
  27. Bao X, Cui J, Wu Y, Han X, Gao C, Hua Z, et al. The roles of endogenous reactive oxygen species and nitric oxide in triptolide-induced apoptotic cell death in macrophages. J. Mol. Med. 2007;85:85–98
  28. Plumb JA, Milroy R, Kaye SB. Effects of the pH dependence of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide-formazan absorption on chemosensitivity determined by a novel tetrazolium-based assay. Cancer Res. 1989;49:4435–4440
  29. Boyer J, Mclean EG, Aroori S, Wilson P, Mcculla A, Carey PD, et al. Characterization of p53 wild-type and null isogenic colorectal cancer cell lines resistant to 5-fluorouracil, oxaliplatin, and irinotecan. Clin. Cancer Res. 2004;10:2158–2167
  30. Bunz F, Hwang PM, Torrance C, Waldman T, Zhang Y, Dillehay L, et al. Disruption of p53 in human cancer cells alters the responses to therapeutic agents. J. Clin. Invest. 1999;104:263–269
  31. Wang W, Mcleod HL, Cassidy J. Disulfiram-mediated inhibition of NF-kappaB activity enhances cytotoxicity of 5-fluorouracil in human colorectal cancer cell lines. Int. J. Cancer. 2003;104:504–511
  32. Zhang Y, Chen F. Reactive oxygen species (ROS), troublemakers between nuclear factor-kappaB (NF-kappaB) and c-Jun NH(2)-terminal kinase (JNK). Cancer Res. 2004;64:1902–1905
  33. Yang S, Chen J, Guo Z, Xu XM, Wang L, Pei XF, et al. Triptolide inhibits the growth and metastasis of solid tumors. Mol. Cancer Ther. 2003;2:65–72
  34. Fidler JM, Li K, Chung C, Wei K, Ross JA, Gao M, et al. PG490-88, a derivative of triptolide, causes tumor regression and sensitizes tumors to chemotherapy. Mol. Cancer Ther. 2003;2:855–862
  35. Brunelle JK, Letai A. Control of mitochondrial apoptosis by the Bcl-2 family. J. Cell Sci. 2009;122:437–441
  36. Fruehauf JP, Meyskens FL. Reactive oxygen species: a breath of life or death?. Clin. Cancer Res. 2007;13:789–794
  37. Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?. Nat. Rev. Drug Discov. 2009;8:579–591
  38. Gloire G, Legrand-Poels S, Piette J. NF-kappaB activation by reactive oxygen species: fifteen years later. Biochem. Pharmacol. 2006;72:1493–1505
  39. Nakano H, Nakajima A, Sakon-Komazawa S, Piao JH, Xue X, Okumura K. Reactive oxygen species mediate crosstalk between NF-kappaB and JNK. Cell Death Differ. 2006;13:730–737

PII: S0304-3835(09)00635-1

doi: 10.1016/j.canlet.2009.10.013

Cancer Letters
Volume 291, Issue 2 , Pages 200-208 , 28 May 2010

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