Abstract
Aim:
To investigate the effects of trans-cinnamaldehyde (TCA) on the human leukemia K562 cell line and the cytotoxicity of cytokine-induced killer (CIK) cells against K562 cells.
Methods:
Apoptosis, Fas expression, and mitochondrial transmembrane potential in K652 cells were analyzed using flow cytometry. K562 cells were labeled with CFSE. The cytotoxic effect of expanded CIK cells on CFSE-labeled K562 cells was determined by FACS flow cytometry.
Results:
Treatment with TCA 180 μmol/L for 9 h induced apoptosis in 8.9%±1.23% of K562 cells. Treatment with 120 or 180 μmol/L TCA for 24 h significantly increased the apoptotic cells to 18.63%±1.42 % and 38.98%±2.74%, respectively. TCA significantly upregulates Fas expression and decreases mitochondrial transmembrane potential in K562 cells. TCA treatment at 120 and 180 μmol/L for 9 h enhanced the percentage of lysis of K562 cells by expanded CIK cells from 34.84%±2.13% to 48.21%±2.22 % and 64.81%±3.22% at the E:F ratio of 25:1 and from 49.26%±3.22% to 57.81%±5.13% and 73.36%±5.98% at E:F ratio of 50:1.
Conclusion:
TCA exerts cytotoxic effects on human leukemia K562 cells by inducing apoptosis and synergizing the cytotoxicity of CIK cells against K562 cells. These properties of TCA are beneficial to the treatment of leukemia, even in the patients who have received hematopoietic stem cells transplantation (HSCT).
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References
Ringdén O . Immunotherapy by allogeneic stem cell transplantation. Adv Cancer Res 2007; 97: 25–60.
Nencioni A, Grünebach F, Patrone F, Ballestrero A, Brossart P . Proteasome: inhibitors antitumor effects and beyond. Leukemia 2007; 21: 30–6.
Ka H, Park HJ, Jung HJ, Choi JW, Cho KS, Ha J, et al. Cinnamaldehyde induces apoptosis by ROS-mediated mitochondrial permeability transition in human promyelocytic leukemia HL-60 cells. Cancer Lett 2003; 196: 143–52.
Lee CW, Lee SH, Lee JW, Ban JO, Lee SY, Yoo HS, et al. 2-hydroxy cinnamaldehyde inhibits SW620 colon cancer cell growth through AP-1 inactivation. J Pharmacol Sci 2007; 104: 19–28.
Koh WS, Yoon SY, Kwon BM, Jeong TC, Nam KS, Han MY . Cinnamaldehyde inhibits lymphocyte proliferation and modulates T-cell differentiation. Int J immunopharmacol 1998; 20: 643–60.
Baker J, Verneris MR, Ito M, Shizuru JA, Negrin RS . Expansion of cytolytic CD8(+) natural killer T cells with limited capacity for graft-versus-host disease induction due to interferon gamma production. Blood 2001; 97: 2923–31.
Introna M, Borleri G, Conti E, Franceschetti M, Barbui AM, Broady R, et al. Repeated infusions of donor-derived cytokine-induced killer cells in patients relapsing after allogeneic stem cell transplantation: a phase I study. Haematologica 2007; 92: 952–59.
Tam YK, Martinson JA, Doligosa K, Klingemann HG . Ex vivo expansion of the highly cytotoxic human natural killer-92 cell-line under current good manufacturing practice conditions for clinical adoptive cellular immunotherapy. Cytotherapy 2003; 5: 259–72.
Cholujová D, Jakubíková J, Kubes M, Arendacká B, Sapák M, Ihnatko R, et al. Comparative study of four fluorescent probes for evaluation of natural killer cell cytotoxicity assays. Immunobiology 2008; 213: 629–40.
Zamai L, Ahmad M, Bennett IM, Azzoni L, Alnemri ES, Perussia B . Natural killer (NK) cell-mediated cytotoxicity: differential use of TRAIL and Fas ligand by immature and mature primary human NK cells. J Exp Med 1998; 188: 2375–80.
Ueda S, Masutani H, Nakamura H, Tanaka T, Ueno M, Yodoi J . Redox control of cell death. Antioxid Redox Signal 2002; 4: 405–14.
Kägi D, Vignaux F, Ledermann B, Bürki K, Depraetere V, Nagata S, et al. Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity. Science 1994; 265: 528–30.
Lowin B, Hahne M, Mattmann C, Tschopp J . Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways. Nature 1994; 370: 650–52.
Verneris MR, Kornacker M, Mailänder V, Negrin RS . Resistance of ex vivo expanded CD3+CD56+ T cells to Fas-mediated apoptosis. Cancer Immunol Immunother 2000; 49: 335–45.
Li W, Wang S, Chen C, Zhuang G . Induction of tumor cell apoptosis via Fas/DR5. Cell Mol Immunol 2006; 3: 467–71.
Yu J, Ren X, Cao S, Zhang W, Hao X . Th1 polarization and apoptosis-inducing activity of CD4+ T-cells in cytokine-induced killers might favor the antitumor cytotoxicity of cytokine-induced killers in vivo. Cancer Biother Radiopharm 2006; 21: 276–84.
Leemhuis T, Wells S, Scheffold C, Edinger M, Negrin RS . A phase I trial of autologous cytokine-induced killer cells for the treatment of relapsed Hodgkin disease and non-Hodgkin lymphoma. Biol Blood Marrow Transplant 2005; 11: 181–7.
Linn YC, Hui KM . Cytokine-induced killer cells: NK-like T cells with cytotolytic specificity against leukemia. Leuk Lymphoma 2003; 44: 1457–62.
Shi M, Zhang B, Tang ZR, Lei ZY, Wang HF, Feng YY, et al. Autologous cytokine-induced killer cell therapy in clinical trial phase I is safe in patients with primary hepatocellular carcinoma. World J Gastroenterol 2004; 10: 1146–51.
Wang ZY, Chen Z . Acute promyelocytic leukemia: from highly fatal to highly curable. Blood 2008; 111: 2505–15.
Torelli GF, Guarini A, Maggio R, Alfieri C, Vitale A, Foà R . Expansion of natural killer cells with lytic activity against autologous blasts from adult and pediatric acute lymphoid leukemia patients in complete hematologic remission. Haematologica 2005; 90: 785–92.
Szczepański T . Why and how to quantify minimal residual disease in acute lymphoblastic leukemia? Leukemia 2007; 21: 622–26.
Acknowledgements
This project was supported by the National Outstanding Young Investigator Program of China (No 30225038).
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Zhang, Jh., Liu, Lq., He, Yl. et al. Cytotoxic effect of trans-cinnamaldehyde on human leukemia K562 cells. Acta Pharmacol Sin 31, 861–866 (2010). https://doi.org/10.1038/aps.2010.76
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DOI: https://doi.org/10.1038/aps.2010.76
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