Abstract
Aim:
To investigate curcumin (diferuloylmethane) induced apoptosis and its molecular mechanism of action in B-NHL cell line Raji cells.
Methods:
Raji cells were cultured in RPMI-1640 medium and treated with curcumin in different concentrations. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium (MTT) assay was used to detect growth inhibition and Hoechst 33258 staining was used to detect apoptosis. Immunocytochemistry and Western blot were used to detect the expressions of histone deacetylase 1, 3, and 8 (HDAC1, HDAC3, and HDAC8) and acetylated histone H4 (Ac-histone H4) protein.
Results:
Curcumin inhibited the proliferation of B-NHL cell line Raji cells with a 36-h IC50 value of 24.1±2.0 μmol/L. Hoechst 33258 staining showed that curcumin could induce Raji cell apoptosis. The expression levels of HDAC1, HDAC3, and HDAC8 proteins were downregulated following curcumin treatment in Raji cells, whereas Ac-histone H4 protein expression was upregulated after treatment with curcumin.
Conclusion:
Curcumin, as a new member of the histone deacetylase inhibitors, can inhibit the expression of class I HDACs (HDAC1, HDAC3, and HDAC8), and can increase the expression of Ac-histone H4 in Raji cells. Curcumin plays an important role in regulating B-NHL cell line Raji cell proliferation and apoptosis.
Similar content being viewed by others
Article PDF
References
Secrist JP, Zhou X, Richon VM . HDAC inhibitors for the treatment of cancer. Curr Opin Invest Drugs 2003; 12: 1422–7.
Hu E, Dul E, Sung CM, Chen Z, Kirkpatrick R, Zhang GF, et al. Identification of novel isoform-selective inhibitors within class I histone deacetylases. J Pharmacol Exp Ther 2003; 307: 720–8.
Buggy JJ, Sideris ML, Mak P, Lorimer DD, McIntosh B, Clark JM . Cloning and characterization of a novel human histone deacetylase, HDAC8. Biochem J 2000; 350: 199–205.
Murata M, Towatari M, Kosugi H . Apoptotic cytotoxic effects of a histone deacetylase inhibitor, FK228, on malignant lymphoid cells. Jpn J Cancer Respondent 2000; 91: 1154–60.
Graessle S, Loidl P, Brosch G . Histone acetylation: plants and fungi as model systems for the investigation of histone deacetylases. Cell Mol Life Sci 2001; 58: 704–20.
Aggarwal BB, Kumar A, Bharti AC . Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Respondent 2003; 23: 363–98.
Leu TH, Maa MC . The molecular mechanisms for the antitumorigenic effect of curcumin. Curr Med Chem Anti-Cancer Agents 2002; 2: 357–70.
Ranjan D, Chen C, Johnston TD, Jeon H, Nagabhushan M . Curcumin inhibits mitogen stimulated lymphocyte proliferation, NFkappaB activation, and IL-2 signaling. J Surg Respondent 2004; 121: 171–7.
Wu L, Xu J, Wu G, Chen Y . Inhibitory effect of curcumin on proliferation of K562 cells involves down-regulation of p210bcr/abl-initiated Ras signal transduction pathway. Acta Pharmacol Sin 2003; 24: 1155–60.
Mariadason JM, Corner GA, Augenlicht LH . Genetic reprogramming in pathways of colonic cell maturation induced by short chain fatty acids: comparison with trichostatin A, sulindac, and curcumin and implications for chemoprevention of colon cancer. Cancer Respondent 2000; 60: 4561–72.
Chen W, Chen Y, Gu J, He J . Effects of curcumin on proliferation of K562 cells involves STAT5 signal transduction pathway. Chin J Hematol 2004; 25: 151–3.
Zhou N, Zhu X, Zhou J, Li M, Zhang X, Huang P, et al. 2-Methoxyestradiol induces cell cycle arrest and apoptosis of nasopharyngeal carcinoma cells. Acta Pharmacol Sin 2004; 25: 1515–20.
Balasubramanyam K, Varier RA, Altaf M, Swaminathan V, Siddappa NB, Ranga U, et al. Curcumin, a novel p300/CBP specific inhibitor of acetyltransferase, represses the acetylation of histones/nonhistone proteins and HAT dependent chromatin transcription. J Biol Chem 2004; 279: 51163–71.
Sullivan SA, Landsman D . Characterization of sequence variability in nucleosome core histone folds. Proteins 2003; 52: 454–65.
Hu E, Chen Z, Fredrickson T, Zhu Y, Kirkpatrick R, Zhang GF, et al. Cloning and characterization of a novel human class I histone deacetylase that functions as a transcription repressor. J Biol Chem 2000; 20: 15254–64.
Yamashita Y, Shimada M, Harimoto N, Rikimaru T, Shirabe K, Tanaka S, et al. Histone deacetylase inhibitor trichostatin A induces cell-cycle arrest/apoptosis and hepatocyte differentiation in human hepatoma cells. Int J Cancer 2003; 103: 572–6.
Author information
Authors and Affiliations
Corresponding author
Additional information
Project supported by the National Natural Science Foundation of China (No 30271672).
Rights and permissions
About this article
Cite this article
Liu, Hl., Chen, Y., Cui, Gh. et al. Curcumin, a potent anti-tumor reagent, is a novel histone deacetylase inhibitor regulating B-NHL cell line Raji proliferation. Acta Pharmacol Sin 26, 603–609 (2005). https://doi.org/10.1111/j.1745-7254.2005.00081.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2005.00081.x
Keywords
This article is cited by
-
Progress in discovery and development of natural inhibitors of histone deacetylases (HDACs) as anti-cancer agents
Naunyn-Schmiedeberg's Archives of Pharmacology (2024)
-
Investigation of in vitro HDAC 1 inhibitory activity of Curcuma longa L. extracts, isolated fractions and curcumin
European Food Research and Technology (2024)
-
Sonodynamic therapy of pancreatic cancer cells based on synergistic chemotherapeutic effects of selenium-PEG-curcumin nanoparticles and gemcitabine
Applied Physics A (2023)
-
Phenolic compounds as histone deacetylase inhibitors: binding propensity and interaction insights from molecular docking and dynamics simulations
Amino Acids (2023)
-
Polyphenols: a route from bioavailability to bioactivity addressing potential health benefits to tackle human chronic diseases
Archives of Toxicology (2023)