Cytotoxic effect of trans-cinnamaldehyde on human leukemia K562 cells - PubMed (original) (raw)

Cytotoxic effect of trans-cinnamaldehyde on human leukemia K562 cells

Jia-hua Zhang et al. Acta Pharmacol Sin. 2010 Jul.

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 micromol/L for 9 h induced apoptosis in 8.9%+/-1.23% of K562 cells. Treatment with 120 or 180 micromol/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 micromol/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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Figures

Figure 1

Figure 1

Chemical structure of TCA.

Figure 2

Figure 2

TCA induced significant apoptosis in K562 cells in a dose-dependent manner at 24 h. A) Original flow cytometry data. Medium supplemented with 0 μmol/L TCA (Control); Medium supplemented with 120 μmol/L TCA (TCA 120); Medium supplemented with 180 μmol/L TCA (TCA 180). B) Percentage of apoptosis in K562 cells. n_=6. Mean±SD. b_P<0.05 vs Control. e_P_<0.05 vs 120 μmol/L TCA.

Figure 3

Figure 3

TCA upregulated expression of Fas/CD95 in K562 cells. A) Effect of TCA treatment for 4 h on expression of Fas/CD95 in K562 cells. B) Effect of TCA treatment for 9 h on expression of Fas/CD95 in K562 cells. C) Effect of TCA treatment for 24 h on expression of Fas/CD95 in K562 cells. n_=5. Mean±SD. b_P<0.05 vs Control. e_P_<0.05 vs 120 μmol/L TCA.

Figure 4

Figure 4

Lysis quantitation by the CFSE/PI assay. A) K562 cells are not distinct in the ungated FSC/SSC dot plot. B) Selection of K562 target cells (R1 gate) according to their CFSE-positivity on the SSC/CFSE dot plot. C) Quantitation of target cell lysis on the CFSE/PI dot plot. Dead K562 cells (R2 gate) are positive for both PI and CFSE.

Figure 5

Figure 5

TCA synergized the cytotoxicity of CIK cells to K562 cells. A) Effect of TCA on cytotoxic activity by CIK cells to K562 cells at the indicated effector:target ratio of 0:1. B) Effect of TCA on cytotoxic activity by CIK cells to K562 cells at the indicated effector: target ratio of 25:1. C) Effect of TCA on cytotoxic activity by CIK cells to K562 at the indicated effector: target ratio of 50:1. n_=5. Mean±SD. b_P<0.05 vs Control. e_P_<0.05 vs 120 μmol/L TCA treated continuously. TCA washout group: target cells were pretreated with TCA for 4 h and then washed out in the presence of CIK cells. TCA continuously treated group: target cells were pretreated with TCA for 4 h and then for another 5 h in the presence of CIK cells.

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