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Triptolide Alters Mitochondrial Functions

  • Conference paper
Oxygen Transport to Tissue XXVIII

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 599))

Abstract

Triptolide (TPL), a small molecule purified from the herb Tripterygium wilfordii, has potential clinical application for suppression of chronic autoimmune disorders and inhibition of tumor growth. However, its mechanism of action is largely unknown. In this study, the effect of TPL on mitochondria was explored with a panel of molecular probes that detect the alteration of mitochondrial functions. When Lewis lung carcinoma (LLC) cells were treated with different doses of TPL for four hours, impaired mitochondrial functions were detected. This included an increased production of reactive oxygen species, the opening of the transition pore of mitochondria, the depolarization of the mitochondria membrane, the inhibition of the production of ATP and increased release of ATP as well as the induction of apoptosis. It is likely that by impairment of mitochondrial function, TPL exerts its inhibitory effect on growth of tumor and progression of inflammatory disease.

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References

  1. S. M. Kupchan, W. A. Court, R. G. Dailey Jr., C. J. Gilmore, R. F. Bryan, Triptolide and tripdiolide, novel antileukemic diterpenoid triepoxides from Tripterygium wilfordii, J. Am. Chem. Soc. 94(20), 7194-7195 (1972).

    Article  PubMed  CAS  Google Scholar 

  2. S. Yang,J. Chen, Z. Guo, X. M. Xu, L. Wang, X. F. Pei,J. Yang, C. B. Underhill, L. Zhang, Triptolide inhibits the growth and metastasis of solid tumors, Mol. Cancer Ther. 2(1), 65-72 (2003).

    Article  CAS  Google Scholar 

  3. T. Tengchaisri, R. Chawengkirttikul, N. Rachaphaew, V. Reutrakul, R. Sangsuwan, S. Sirisinha, Antitumor activity of triptolide against cholangiocarcinoma growth in vitro and in hamsters, Cancer Lett. 133(2), 169-175 (1998).

    Article  PubMed  CAS  Google Scholar 

  4. Y. S. Wei, I. Adachi, Inhibitory effect of triptolide on colony formation of breast and stomach cancer cell lines, Chung Kuo. Yao. Li. Hsueh. Pao. 12(5), 406-410 (1991).

    PubMed  CAS  Google Scholar 

  5. X. Tao, P. E. Lipsky, The Chinese anti-inflammatory and immunosuppressive herbal remedy Tripterygium wilfordiiHook. f., Rheum. Dis. Clin. North Amer. 26, 29-50 (2000).

    Article  CAS  Google Scholar 

  6. X. Tao, J. J. Cush, M. Garret, P. E. Lipsky, A Phase I study of ethyl acetate extract of the Chinese antirheumatic herb Tripterygium wilfordiiHook. f. in rheumatoid arthritis. J. Rheumatol. 28, 2160-2167 (2001).

    PubMed  CAS  Google Scholar 

  7. X. C. Tao, V. Pinyopornpanit, J. Younger, J. J. Cai, Y. Mao, L. Ma, S. Chang, P. E. Lipsky, A Phase I/II double-blind, placebo-controlled trial of an extract of Tripterygium wilfordiiHook f. shows benefit in patients with rheumatoid arthritis. Abstract, American College of Rheumatology, 65th Ann. Mtg., San Francisco, CA., Nov. 11-17, 2001. Arthritis Rheum. 44(suppl.).

    Google Scholar 

  8. J. L. Faul, T. Nishimura, G. J. Berry, G. V. Benson, R. G. Pearl, P. N. Kao, Triptolide attenuates pulmonary arterial hypertension and neointimal formation in rats, Am. J. Respir. Crit. Care Med. 162(6), 2252-2258 (2000).

    PubMed  CAS  Google Scholar 

  9. G. Krishna, K. Liu, H. Shigemitsu, M. Gao, T. A. Raffin, G. D. Rosen, PG490-88, a derivative of triptolide, blocks bleomycin-induced lung fibrosis, Am. J. Pathol. 158(3), 997-1004 (2001).

    PubMed  CAS  Google Scholar 

  10. E. W. Chan, S. C. Cheng, F. W. Sin, Y. Xie, Triptolide induced cytotoxic effects on human promyelocytic leukemia, T cell lymphoma and human hepatocellular carcinoma cell lines, Toxicol. Lett. 122(1), 81-87 (2001).

    Article  PubMed  CAS  Google Scholar 

  11. H. Liu, Z. H. Liu, Z. H. Chen, J. W. Yang, L. S. Li, Triptolide: a potent inhibitor of NF-kappa B in T-lymphocytes. Acta Pharmacol. Sin. 21(9), 782-786 (2000).

    PubMed  CAS  Google Scholar 

  12. G. Zhao, L. T. Vaszar, D. Qiu, L. Shi, P. N. Kao, Anti-inflammatory effects of triptolide in human bronchial epithelial cells, Am. J. Physiol. Lung Cell Mol. Physiol. 279(5), L958-L966 (2000).

    CAS  Google Scholar 

  13. B. J. Chen, C. Liu, X. Cui, J. M. Fidler, N. J. Chao, Prevention of graft-versus-host disease by a novel immunosuppressant, PG490-88, through inhibition of alloreactive T cell expansion, Transplantation 70 (10), 1442-1447 (2000).

    Article  PubMed  CAS  Google Scholar 

  14. D. Qiu, G. Zhao, Y. Aoki, L. Shi, A. Uyei, S. Nazarian, J. C. Ng, P. N. Kao, 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. 274(19), 13443-13450 (1999).

    Article  PubMed  CAS  Google Scholar 

  15. N. Dias, C. Bailly, Drugs targeting mitochondrial functions to control tumor cell growth, Biochem. Pharmacol. 70(1), 1-12 (2005).

    Article  PubMed  CAS  Google Scholar 

  16. R. Kim, Recent advances in understanding the cell death pathways activated by anticancer therapy, Cancer 103(8), 1551-1560 (2005).

    Article  PubMed  CAS  Google Scholar 

  17. T. Asakura, K. Ohkawa, Chemotherapeutic agents that induce mitochondrial apoptosis, Curr. Cancer Drug Targets 4(7), 577-590 (2004).

    Article  PubMed  CAS  Google Scholar 

  18. T. Tengchaisri, R. Chawengkirttikul, N. Rachaphaew, V. Reutrakul, R. Sangsuwan, S. Sirisinha, Antitumor activity of triptolide against cholangiocarcinoma growth in vitro and in hamsters, Cancer Lett. 133(2), 169-175 (1998).

    Article  PubMed  CAS  Google Scholar 

  19. Y. S. Wei, I. Adachi, Inhibitory effect of triptolide on colony formation of breast and stomach cancer cell lines, Chung Kuo. Yao. Li. Hsueh. Pao. 12(5), 406-410 (1991).

    PubMed  CAS  Google Scholar 

  20. J. Y. Xu, J. Yang, L. Z. Li, Antitumor effect of Tripterygium wilfordii, Chung Kuo. Chung His. I. Chieh Ho. Tsa. Chih. 12(3), 161 (1992).

    CAS  Google Scholar 

  21. W. Z. Gu, S. R. Brandwein, Inhibition of type II collagen-induced arthritis in rats by triptolide, Int. J. Immunopharmacol. 20(8), 389-400 (1998).

    Article  PubMed  CAS  Google Scholar 

  22. The Invitrogen online catalog, accessed 6/18/05. http://probes.invitrogen.com/media/publications/508.pdf

    Google Scholar 

  23. V. Petronilli, G. Miotto, M. Canton, M. Brini, R. Colonna, P. Bernardi, F. Di Lisa, Transient and long-lasting openings of the mitochondrial permeability transition pore can be monitored directly in intact cells by changes in mitochondrial calcein fluorescence, Biophys. J. 76(2), 725-734 (1999).

    Article  PubMed  CAS  Google Scholar 

  24. V. Petronilli, G. Miotto, M. Canton, R. Colonna, P. Bernardi, F. Di Lisa, Imaging the mitochondrial permeability transition pore in intact cells, Biofactors 8(3-4), 263-272 (1998).

    PubMed  CAS  Google Scholar 

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Su, Y., Yang, S., Xiao, Z., Wang, W., Okunieff, P., Zhang, L. (2008). Triptolide Alters Mitochondrial Functions. In: Maguire, D.J., Bruley, D.F., Harrison, D.K. (eds) Oxygen Transport to Tissue XXVIII. Advances in Experimental Medicine and Biology, vol 599. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-71764-7_19

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