Korean J Hematol.  2005 Jun;40(2):75-81. 10.5045/kjh.2005.40.2.75.

Apoptosis Induction by Curcumin in Human Myelogenous Leukemia Cell Lines

• Cho YH
• Kim YJ
• Park JW
• Ahn KS
• Kim IH
• Bae EK
• Park SY
• Kim BK
• Yoon SS

• KMID: 2252341
• DOI: http://doi.org/10.5045/kjh.2005.40.2.75

Abstract

BACKGROUND
Curcumin, a naturally occurring biologically active compound extracted from rhizomes of Curcuma species, has been shown to possess potent anti-inflammatory, anti-tumor and anti-oxidative properties. The effects and possible mechanism of this agent were investigated on 2 human myelogenous leukemic cell lines.
METHODS
K562 and KG-1 cells were the two cell lines selected. The MTT assay and flow cytometry were used to assess the cytotoxicity and for cell cycle analysis, respectively. The protein expressions were analyzed by Western blotting; the caspase activity was also checked.
RESULTS
Both cell lines showed dose-dependent susceptibility to curcumin, and the cell cycle analysis showed an increased sub-G1 phase in the KG-1 cells. In the K562 cell, curcumin down regulated the expressions of PCNA (proliferating cell nuclear antigen) and cyclins D1 and B1. The expression of Akt was also down-regulated, but caspase-3 was activated to induce cleaved PARP (polyadenosine ribose polymerase) and apoptosis. However, the expression of phospho-Erk was unaffected. Co-treatment of cyclosporin A (CsA) with curcumin resulted in an attenuation of apoptosis in the K562 cells, implying curcumin-induced apoptosis is dependent on the release of cytochrome c from the mitochondria.
CONCLUSION
Curcumin induced cell cycle arrest and apoptosis in both human myelogenous leukemic cell lines, with the apoptosis appearing to be dependent on the release of cytochrome c from the mitochondria.

Keyword

Curcumin; Myelogenous leukemia; Apoptosis

MeSH Terms

Apoptosis*
Blotting, Western
Caspase 3
Cell Cycle
Cell Cycle Checkpoints
Cell Line*
Curcuma
Curcumin*
Cyclins
Cyclosporine
Cytochromes c
Flow Cytometry
Humans*
K562 Cells
Leukemia, Myeloid*
Mitochondria
Proliferating Cell Nuclear Antigen
Rhizome
Ribose
Caspase 3
Curcumin
Cyclins
Cyclosporine
Cytochromes c
Proliferating Cell Nuclear Antigen
Ribose

Figure

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  Fig. 1. Chemical structure of curcumin.

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  Fig. 2. Dose and time dependency of curcumin effect on the leukemic cell line K562 and KG-1. Curcumin was treated at various concentrations and times (A) and then its concentration was fixed at 25μM (B). C urcumin at 110～130μM concentration reduced cell viability by 45～50% and KG-1 showed more time-dependent pattern of cytotoxicity to curcumin.

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  Fig. 3. The effect of curcumin on the cell cycle progression. K562 and KG-1 were PI stained at 24hrs, 48hrs, 72hrs after treatment with curcumin 10μM. KG-1 cells in sub-G1 phase were increased at 24hrs, but K562 cells appeared not affected.

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  Fig. 4. Western blot results of cyclin D1, cdk4 at curcumin 10μM. The expressions of cdk4 and cyclin D1 were not decreased in K562 cells at this concentration.

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  Fig. 5. C urcumin effect on cell cycle and apoptosis. curcumin caused decreased expression of cyclin D1, B1, and PCNA but not cyclin A at after treatment of curcumin at 100 μM for 6hours in K562 cells. Apoptosis was induced by curcumin exposure of either 100μM for 6hours or 25μM for 24hrs.

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  Fig. 6. The expression of phospho-Erk Akt, bcl-2 after treatment with curcumin at 25μMAkt was decreased within an hour and bcl-2 was also reduced rapidly in KG-1 cell. However, phospho-Erk was not affected by curcumin.

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  Fig. 7. Activity of caspase 3 treated with various concentrations of curcumin, cyclosporin A (C sA), and cyclosporin A+ curcumin in K562 cell.

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