Abstract
As one of the active compounds derived from Traditional Chinese Medicine, Celastrol (CSL) had cytotoxicity for human leukemia cancer cells K562 and its multidrug-resistant cell line K562/A02. Here, we introduced cysteamine-modified CdTe QDs as the labeling and drug carrier into CSL research and found that the self-assembly and conjugation of anticancer molecular CSL with the Cys-CdTe QDs could significantly increase the drug’s cytotoxicity for K562 cells. More important, these CSL-Cys-CdTe nanocomposites could overcome the multidrug resistance of K562/A02 cells and efficiently inhibit the cancer cell proliferation by realizing the pH-sensitive responsive release of CSL to cancer cells. The enhanced cytotoxicity was caused by the increase of the G2/M phase arrest for K562/A02 cells as well as for K562 cells. Cys-CdTe QDs can readily bind on the cell plasma membranes and be internalized into cancer cells to trace and detect human leukemia cancer cells in real time. In addition, these Cys-CdTe QDs can facilitate the inhibition of the multidrug resistance of K562/A02 cells and readily induce apoptosis. As a good photosensitizer for the therapy, labeling, and tracing of cancer cells, the combination of CSL with Cys-CdTe QDs can optimize the use of and a new potential therapy method for CSL and yield new tools to explore the mechanisms of active compounds from Traditional Chinese Medicine.
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References
Nam NH, Parang K. Current targets for anticancer drug discovery. Curr Drug Targets, 2003, 4: 159–179
Li YY, Zhang T, Schwartzb SJ, Sun D. New developments in Hsp90 inhibitors as anti-cancer therapeutics: mechanisms, clinical perspective and more potential. Drug Resist Updat, 2009, 12: 17–27
Litman T, Nielsen D, Skovsgaard T, Zeuthen T, Stein WD. ATPase activity of P-glycoprotein related to emergence of drug resistance in Ehrlich ascites tumor cell lines. Biochim Biophys Acta, 1997, 1361: 147–158
Li JY, Chen C, Wang XM, Gu ZZ, Chen BA. Novel strategy to fabricate PLA/Au nanocomposites as an efficient drug carrier for human leukemia cells in vitro. Nanoscale Res Lett, 2011, 6: 29
Wu W, Wieckowski S, Pastorin G, Benincasa M, Klumpp C, Briand J P, Gennaro R, Prato M, Bianco A. Targeted delivery of amphotericin B to cells by using functionalized carbon nanotubes. Angew Chem Int Edit, 2005, 44: 6358–6362
Cohen I, Tagliaferri M, Tripathy D. Traditional Chinese medicine in the treatment of breast cancer. Semin Oncol, 2002, 29: 563–574
Yang HJ, Chen D, Cui QC, Yuan X, Dou QP. Celastrol, a triterpene extracted from the Chinese “thunder of god vine,” is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice. Cancer Res, 2006, 66: 4578–4765
Tao X, Younger J, Fan FZ, Wang B, Lipsky PE. Benefit of an extract of tripterygium wilfordii Hook F in patients with rheumatoid arthritis: a double-blind, placebocontrolled study. Arthritis Rheum, 2002, 46: 735–743
Kang SW, Kim MS, Kim HS, Kim Y, Shin D, Park JH, Kang YH. Celastrol attenuates adipokine resistin-associated matrix interaction and migration of vascular smooth muscle cells. J cell biochem, 2013, 114: 398–408
Li H, Zhang YY, Huang XY, Sun YN, Jia YF, Li D. Beneficial effect of tripterine on systemic lupus erythematosus induced by active chromatin in BALB/c mice. Eur J Pharmacol, 2005, 512: 231–237
Kang H, Lee M, Jang SW. Celastrol inhibits TGF-beta 1-induced epithelial-mesenchymal transition by inhibiting Snail and regulating E-cadherin expression. Biochem Biophys Res Commun, 2013, 437: 550–556
Li GQ, Zhang Y, Liu D, Qian YY, Zhang H, Guo SY, Sunagawa M, Hisamitsu T, Liu YQ. Celastrol inhibits interleukin-17A-stimulated rheumatoid fibroblast-like synoviocyte migration and invasion through suppression of NF-kB-mediated matrix metalloproteinase-9 expression. Int immunopharmacol, 2012, 14: 422–431
Allison AC, Cacabelos R, Lombardi VR, Alvarez XA, Vigo C. Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry, 2001, 25: 1341–1357
Nagase M, Oto J, Sugiyama S, Yube K, Takaishi Y, Sakato N. Apoptosis induction in HL-60 cells and inhibition of topoisomerase II by triterpene celastrol. Biosci Biotechnol Biochem, 2003, 67: 1883–1887
Lee JH, Koo TH, Yoon H, Jung HS, Jin HZ, Lee K, Hong YS, Lee JJ. Inhibition of NF-kB activation through targeting IkB kinase by celastrol, a quinone methide triterpenoid. Biochem Pharm, 2006, 72: 1311–1321
Sethi G, Ahn KS, Pandey MK, Aggarwal BB. Celastrol, a novel triterpene, potentiates TNF-induced apoptosis and suppresses invasion of tumor cells by inhibiting NF-kB-regulated gene products and TAK1-mediated NF-kB activation. Blood, 2007, 109: 2727–2735
Katz E, Willner I. Integrated nanoparticle-biomolecule hybrid systems: synthesis, properties, and applications. Angew Chem Int Ed, 2004, 43: 6042–6108
Kong RM, Chen Z, Ye M, Zhang XB, Tan WH. Cell-SELEX-based aptamer-conjugated nanomaterials for enhanced targeting of cancer cells. Sci China Chem, 2011, 54(8): 1218–1226
Wang SG, Li YX, Bai J, Yang QB, Song Y, Zhang CQ. Characterization and photoluminescence studies of CdTe nanoparticles before and after transfer from liquid phase to polystyrene. Bull Mater Sci, 2009, 32: 487–491
Li J, Hong X, Liu Y, Wang YW, Li JH, Bai YB, Li TJ. Highly photoluminescent CdTe/PNIPAM temperature sensitive gels. Adv Mater, 2005, 17: 163–166
Zhang H, Zhou Z, Liu K, Wang RB, Yang B. Controlled assembly of fluorescent multilayers from an aqueous solution of CdTe nanocrystals and nonionic carbazole-containing copolymers. J Mater Chem, 2003, 13: 1356–1361
Ji Y, Li BQ, Ge SR, Sokolov JC, Rafailovich MH. Structure and nanomechanical characterization of electrospun PS/clay nanocomposite fibers. Langmuir, 2006, 22: 1321–1328
Zhao L, Cao JT, Wu ZQ, Li JX, Zhu JJ. Lab-on-a-chip for anticancer drug screening using quantum dots probe based apoptosis assay. J Nanomed Nanotechnol, 2013, 9: 348–356
Michalet X, Pinaud FF, Bentolila LA, Tsay JM, Doose S, Li JJ, Sundaresan G, Wu AM, Gambhir SS, Weiss S. Quantum dots for live cells, in vivo imaging, and diagnostics. Science, 2005, 307: 538-544
Liu JB, Yang XH, He XX, Wang KM, Wang Q, Guo QP, Shi H, Huang J, Huo XQ. Fluorescent nanoparticles for chemical and biological sensing. Sci China Chem, 2011, 54: 1157–1176
Hoshino A, Hanaki K, Suzuki K, Yamamoto K. Applications of T-lymphoma labeled with fluorescent quantum dots to cell tracing markers in mouse body. Biochem Biophys Res Commun, 2004, 314: 46–53
Lovric J, Bazzi HS, Cuie Y, Fortin GA, Winnik FM, Maysinger D. Differences in subcellular distribution and toxicity of green and red emitting CdTe quantum dots. J Mol Med, 2005, 83: 377–385
Gaponik N, Talapin DV, Rogach AL, Hoppe K, Shevchenko EV, Kornowski A, Eychmüller A, Weller H. Thiol-capping of CdTe nanocrystals: an alternative to organometallic synthetic routes. J Phys Chem B, 2002, 106: 7177–7185
Li JY, Wu CY, Xu PP, Shi LX, Chen BA, Selke M, Jiang H, Wang XM. Multifunctional effects of Cys-CdTe QDs conjugated with gambogic acid for cancer cell tracing and inhibition. RSC Adv, 2013, 3: 6518–6525
Li JY, Wu CH, Gao F, Zhang RY, Lv G, Fu DG, Chen BA, Wang XM. In vitro study of drug accumulation in cancer cells via specific association with CdS nanoparticles. Bioorg Med Chem Lett, 2006, 16: 4808–4812
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Li, J., Shi, L., Shao, Y. et al. The cellular labeling and pH-sensitive responsive-drug release of celastrol in cancer cells based on Cys-CdTe QDs. Sci. China Chem. 57, 833–841 (2014). https://doi.org/10.1007/s11426-014-5092-0
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DOI: https://doi.org/10.1007/s11426-014-5092-0