Curcumin-induced histone acetylation in malignant hematologic cells

Abstract

This study investigated the inhibitory effects of curcumin on proliferation of hematological malignant cells in vitro and the anti-tumor mechanism at histone acetylation/histone deacetylation levels. The effects of curcumin and histone deacetylase inhibitor trichostatin A (TSA) on the growth of Raji cells were tested by MTT assay. The expression of acetylated histone-3 (H₃) in Raji, HL60 and K562 cells, and peripheral blood mononuclear cells (PBMCs) treated with curcumin or TSA was detected by immunohistochemistry and FACS. The results showed curcumin inhibited proliferation of Raji cells significantly in a time- and dose-dependent fashion, while exhibited low toxicity in PBMCs. Curcumin induced up-regulation of the expression of acetylated H₃ dose-dependently in all malignant cell lines tested. In conclusion, curcumin inhibited proliferation of Raji cells selectively, enhanced the level of acetylated (H₃) in Raji, HL60, and K562 cells, which acted as a histone deacetylase inhibitor like TSA. Furthermore, up-regulation of H₃ acetylation may play an important role in regulating the proliferation of Raji cells.

Keywords

curcumin / histone acetylation / histone deacetylation

References

[1] DingZ.S., GaoC.X., ChenN.B., et al. . Effects of curcumin: antiangiogenesis and induction of SMMC-7721 cell apoptosis. Chin Pharmacol Bulletin (Chinese), 2003, 19(2): 171-173

[2] CressW.D., SetoE.. Histone deacetylase transcription control, and cancer. J Cell Physiol, 2000, 184: 1-16

[3] SasakawaY., NaoeY., InoueT., et al. . Effects of FK228, a novel histone deacetylase inhibitor, on human lymphoma U-937 cells in vitro and in vivo. Biochem Pharmacol, 2002, 64(7): 1079-1090

[4] PiekarzR.L., RobeyR., SandorV., et al. . Inhibitors of histone deacetylation, depsipeptide (FR901228), in the treatment of peripheral and cutaneous T-cell lymphoma: a case in report. Blood, 2001, 98: 2865-2868

[5] ChenW.J., ChenY., WuY.D., et al. . Effect of curcumin on expression of cell cycle related proteins in HL-60 cell line. J Clin Hematol (Chinese), 2001, 14(5): 215-217

[6] GuiC.Y., NgoL., XuW.S., et al. . Histone deacetylase (HDAC) inhibitor activation of p21WAF1 involves changes in promoter-associated proteins, including HDAC1. Proc Natl Acad Sci U S A, 2004, 101(5): 1241-1246

[7] HanS.S., ChungS.T., RobertsonD.A., et al. . Curcumin causes the growth arrest and apoptosis of B cell lymphoma by downregulation of egr-1, C-myc, Bcl-xl, NF-κB and P53. Clin Immunol, 1999, 93(2): 152-161

[8] AggarwalB.B., KumarA., BhartiA.C., et al. . Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res, 2003, 23(1A): 363-398

[9] FinninM.S., DonigianJ.R., CohenA., et al. . Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors. Nature, 1999, 401(6749): 188-193

[10] ZhouQ., MelkoumianZ.K., LucktongA.. Rapid induction of histone hyperacetylation and cellular differentiation in human breast tumor cell lines following degradation of histone deacetylase-1. J Biol Chem, 2000, 275(45): 35 256-35 263

[11] LiuH.L., ChenY., CuiG.H., et al. . Curcumin, a potent anti-tumor reagent, is a novel histone deacetylase inhibitor regulating B-NHL cell line Raji proliferation. Acta Pharmacol Sin, 2005, 26(5): 603-609