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Evidence-Based Complementary and Alternative Medicine
Volume 2013, Article ID 818709, 11 pages
http://dx.doi.org/10.1155/2013/818709
Research Article

Integration of Different “-omics” Technologies Identifies Inhibition of the IGF1R-Akt-mTOR Signaling Cascade Involved in the Cytotoxic Effect of Shikonin against Leukemia Cells

1Institute of Pharmacy and Biochemistry, Department of Pharmaceutical Biology, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany
2Agricultural Biotechnology Research Center, Academia Sinica, 115 Taipei, Taiwan
3Cytometry Core Facility, Institute of Molecular Biology, Ackermannweg 4, 55128 Mainz, Germany
4HanseMerkur Center for Traditional Chinese Medicine at the University Medical Center Eppendorf, 20246 Hamburg, Germany

Received 18 March 2013; Accepted 7 May 2013

Academic Editor: Sookyung Lee

Copyright © 2013 Benjamin Wiench et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. B. J. Druker, S. Tamura, E. Buchdunger et al., “Effects of a selective inhibitor of the Ab1 tyrosine kinase on the growth of Bcr-Ab1 positive cells,” Nature Medicine, vol. 2, no. 5, pp. 561–566, 1996. View at Google Scholar · View at Scopus
  2. D. G. Maloney, A. J. Grillo-López, C. A. White et al., “IDEC-C2B8 (rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma,” Blood, vol. 90, no. 6, pp. 2188–2195, 1997. View at Google Scholar · View at Scopus
  3. F. Bertolini, “Lenalidomide for multiple myeloma,” The New England Journal of Medicine, vol. 367, pp. 573–575, 2012. View at Google Scholar
  4. W. J. Norde, W. Hobo, R. van der Voort, and H. Dolstra, “Coinhibitory molecules in hematologic malignancies: targets for therapeutic intervention,” Blood, vol. 120, pp. 728–736, 2012. View at Google Scholar
  5. A. M. Martelli, F. Chiarini, C. Evangelisti et al., “Targeting the liver kinase B1/AMP-activated protein kinase pathway as a therapeutic strategy for hematological malignancies,” Expert Opinion on Therapeutic Targets, vol. 16, pp. 729–742, 2012. View at Google Scholar
  6. X. Chen, L. Yang, J. J. Oppenheim, and M. Z. Howard, “Cellular pharmacology studies of shikonin derivatives,” Phytotherapy Research, vol. 16, pp. 199–209, 2002. View at Google Scholar
  7. B. Wiench, T. Eichhorn, M. Paulsen, and T. Efferth, “Shikonin directly targets mitochondria and causes mitochondrial dysfunction in cancer cells,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 726025, 15 pages, 2012. View at Publisher · View at Google Scholar
  8. T. G. Klenø, B. Kiehr, D. Baunsgaard, and U. G. Sidelmann, “Combination of &omics' data to investigate the mechanism(s) of hydrazine-induced hepatotoxicity in rats and to identify potential biomarkers,” Biomarkers, vol. 9, no. 2, pp. 116–138, 2004. View at Publisher · View at Google Scholar · View at Scopus
  9. S. Mizuarai, H. Irie, D. M. Schmatz, and H. Kotani, “Integrated genomic and pharmacological approaches to identify synthetic lethal genes as cancer therapeutic targets,” Current Molecular Medicine, vol. 8, no. 8, pp. 774–783, 2008. View at Publisher · View at Google Scholar · View at Scopus
  10. F. Meric-Bernstam and A. M. Gonzalez-Angulo, “Targeting the mTOR signaling network for cancer therapy,” Journal of Clinical Oncology, vol. 27, pp. 2278–2287, 2009. View at Google Scholar
  11. G. G. Chiang and R. T. Abraham, “Targeting the mTOR signaling network in cancer,” Trends in Molecular Medicine, vol. 13, pp. 433–442, 2007. View at Google Scholar
  12. C. G. Proud, “mTORC1 signalling and mRNA translation,” Biochemical Society Transactions, vol. 37, pp. 227–231, 2009. View at Google Scholar
  13. A. C. Hsieh, Y. Liu, M. P. Edlind et al., “The translational landscape of mTOR signalling steers cancer initiation and metastasis,” Nature, vol. 485, pp. 55–61, 2012. View at Google Scholar
  14. N. Chapuis, J. Tamburini, A. S. Green et al., “Perspectives on inhibiting mTOR as a future treatment strategy for hematological malignancies,” Leukemia, vol. 24, no. 10, pp. 1686–1699, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. B. Chabner and D. Longo, Cancer Chemotherapy and Biotherapy: Principles and Practice, Lippincott Williams and Wilkins.
  16. A. R. Tee, B. D. Manning, P. P. Roux, L. C. Cantley, and J. Blenis, “Tuberous sclerosis complex gene products, tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb,” Current Biology, vol. 13, no. 15, pp. 1259–1268, 2003. View at Publisher · View at Google Scholar · View at Scopus
  17. M. Laplante and D. M. Sabatini, “mTOR signaling in growth control and disease,” Cell, vol. 149, pp. 274–293, 2012. View at Google Scholar
  18. E. J. Brown, M. W. Albers, T. B. Shin et al., “A mammalian protein targeted by G1-arresting rapamycin-receptor complex,” Nature, vol. 369, pp. 756–758, 1994. View at Google Scholar
  19. S. Vignot, S. Faivre, D. Aguirre, and E. Raymond, “mTOR-targeted therapy of cancer with rapamycin derivatives,” Annals of Oncology, vol. 16, pp. 525–537, 2005. View at Google Scholar
  20. K. E. O'Reilly, F. Rojo, Q. B. She et al., “mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt,” Cancer Research, vol. 66, no. 3, pp. 1500–1508, 2006. View at Publisher · View at Google Scholar · View at Scopus
  21. J. Tamburini, N. Chapuis, V. Bardet et al., “Mammalian target of rapamycin (mTOR) inhibition activates phosphatidylinositol 3-kinase/Akt by up-regulating insulin-like growth factor-1 receptor signaling in acute myeloid leukemia: rationale for therapeutic inhibition of both pathways,” Blood, vol. 111, no. 1, pp. 379–382, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. X. Wan, B. Harkavy, N. Shen, P. Grohar, and L. J. Helman, “Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism,” Oncogene, vol. 26, no. 13, pp. 1932–1940, 2007. View at Publisher · View at Google Scholar · View at Scopus
  23. O. Trott and A. J. Olson, “Software news and update AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading,” Journal of Computational Chemistry, vol. 31, no. 2, pp. 455–461, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. F. Singh, D. Gao, M. G. Lebwohl, and H. Wei, “Shikonin modulates cell proliferation by inhibiting epidermal growth factor receptor signaling in human epidermoid carcinoma cells,” Cancer Letters, vol. 200, no. 2, pp. 115–121, 2003. View at Publisher · View at Google Scholar · View at Scopus
  25. U. Rix and G. Superti-Furga, “Target profiling of small molecules by chemical proteomics,” Nature Chemical Biology, vol. 5, pp. 616–624, 2009. View at Google Scholar
  26. M. Pollak, “The insulin and insulin-like growth factor receptor family in neoplasia: an update,” Nature Reviews Cancer, vol. 12, pp. 159–169, 2012. View at Google Scholar
  27. A. M. Martelli, F. Chiarini, C. Evangelisti et al., “Two hits are better than one: targeting both phosphatidylinositol 3-kinase and mammalian target of rapamycin as a therapeutic strategy for acute leukemia treatment,” Oncotarget, vol. 3, pp. 371–394, 2012. View at Google Scholar
  28. S. Park, N. Chapuis, F. Saint Marcoux et al., “A phase Ib GOELAMS study of the mTOR inhibitor RAD001 in association with chemotherapy for AML patients in first relapse,” Leukemia, 2013. View at Publisher · View at Google Scholar
  29. A. M. Martelli, P. L. Tazzari, C. Evangelisti et al., “Targeting the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin module for acute myelogenous leukemia therapy: from bench to bedside,” Current Medicinal Chemistry, vol. 14, no. 19, pp. 2009–2023, 2007. View at Publisher · View at Google Scholar · View at Scopus
  30. D. Barrett, V. I. Brown, S. A. Grupp, and D. T. Teachey, “Targeting the PI3K/AKT/mTOR signaling axis in children with hematologic malignancies,” Pediatric Drugs, vol. 14, pp. 299–316, 2012. View at Google Scholar
  31. S. Amadori, R. Stasi, A. M. Martelli et al., “Temsirolimus, an mTOR inhibitor, in combination with lower-dose clofarabine as salvage therapy for older patients with acute myeloid leukaemia: results of a phase II GIMEMA study (AML-1107),” British Journal of Haematology, vol. 156, pp. 205–212, 2012. View at Google Scholar
  32. B. Li, S. Gao, F. Wei, A. C. Bellail, C. Hao, and T. Liu, “Simultaneous targeting of EGFR and mTOR inhibits the growth of colorectal carcinoma cells,” Oncology Reports, vol. 28, pp. 15–20, 2012. View at Google Scholar
  33. Y. Sanchez, G. P. Simon, E. Calvino, E. de Blas, and P. Aller, “Curcumin stimulates reactive oxygen species production and potentiates apoptosis induction by the antitumor drugs arsenic trioxide and lonidamine in human myeloid leukemia cell lines,” Journal of Pharmacology and Experimental Therapeutics, vol. 335, pp. 114–123, 2010. View at Google Scholar
  34. J. O'Brien, I. Wilson, T. Orton, and F. Pognan, “Investigation of the Alamar Blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity,” European Journal of Biochemistry, vol. 267, no. 17, pp. 5421–5426, 2000. View at Publisher · View at Google Scholar · View at Scopus
  35. J. Eberwine, H. Yeh, K. Miyashiro et al., “Analysis of gene expression in single live neurons,” Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 7, pp. 3010–3014, 1992. View at Google Scholar · View at Scopus
  36. C. J. Chen, M. C. Tseng, H. J. Lin, T. W. Lin, and Y. R. Chen, “Visual indicator for surfactant abundance in MS-based membrane and general proteomics applications,” Analytical Chemistry, vol. 82, pp. 8283–8290, 2010. View at Google Scholar
  37. W. H. Chang, C. Y. Lee, C. Y. Lin et al., “UniQua: a universal signal processor for MS-based qualitative and quantitative proteomics applications,” Analytical Chemistry, vol. 85, pp. 890–897, 2013. View at Google Scholar