Abstract
Citral, 3,7-dimethyl-2,6-octadienal, is a key component of the essential oils extracted from several lemon-scented herbal plants. Besides its antifungal activity, the anticancer effect of citral was studied in recent years. In this study, we investigated the effect of citral on the acute promyelocytic leukemia cell line NB4. Citral treatment had an antiproliferative effect in NB4 cells via the induction of apoptosis assessed by morphology, proliferation assay, DNA electrophoresis, Annexin V-FITC/PI staining and caspase-3 activation. And citral induced apoptosis of NB4 cells in a dose- and time-dependent manner. In addition, citral treatment induced decreased mitochondrial membrane potential, indicating that citral induced apoptosis via the mitochondrial pathway. Bax up-regulation and Bcl-2 down-regulation on mRNA level and NF-κB down-regulation on protein level was found in this study, suggesting that Bcl-2, Bax and NF-κB may be involved in the mechanism of the apoptotic effect of citral on NB4 cells. These data suggest that citral has a potential therapeutic effect on leukemia.
Similar content being viewed by others
References
Adams JM (2003) Ways of dying: multiple pathways to apoptosis. Genes Dev 17:2481–2495
Bargou RC, Emmerich F, Krappmann D, Bommert K, Mapara MY, Arnold W, Royer HD, Grinstein E, Greiner A, Scheidereit C, Dorken B (1997) Constitutive nuclear factor-kappaB-RelA activation is required for proliferation and survival of Hodgkin’s disease tumor cells. J Clin Investig 100:2961–2969
Chaouki W, Leger DY, Liagre B, Beneytout JL, Hmamouchi M (2009) Citral inhibits cell proliferation and induces apoptosis and cell cycle arrest in MCF-7 cells. Fundam Clin Pharmacol 23:549–556
Cohen JJ (1999) Apoptosis: mechanisms of life and death in the immune system. J Allergy Clin Immunol 103:548–554
Dudai N, Weinstein Y, Krup M, Rabinski T, Ofir R (2005) Citral is a new inducer of caspase-3 in tumor cell lines. Planta Med 71:484–488
Gilmore TD, Koedood M, Piffat KA, White DW (1996) Rel/NF-kappaB/IkappaB proteins and cancer. Oncogene 13:1367–1378
Indran IR, Tufo G, Pervaiz S (2011) Brenner C Recent advances in apoptosis, mitochondria and drug resistance in cancer cells. Biochim Biophys Acta 1807:735–745
Karin M, Greten FR (2005) NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev 5:749–759
Luo M, Jiang LK, Huang YX, Xiao M, Li B, Zou GL (2004) Effects of citral on Aspergillus flavus spores by quasi-elastic light scattering and multiplex microanalysis techniques. Acta Biochim Biophys Sin 36:277–283
McGill G, Fisher DE (1997) Apoptosis in tumorigenesis and cancer therapy. Front Biosci 2:d353–d379
McKeithan TW, Takimoto GS, Ohno H, Bjorling VS, Morgan R, Hecht BK, Dube I, Sandberg AA, Rowley JD (1997) BCL3 rearrangements and t (14;19) in chronic lymphocytic leukemia and other B-cell malignancies: a molecular and cytogenetic study. Genes Chromosomes Cancer 20:64–72
Mendonca Ade L, da Silva CE, de Mesquita FL, Campos Rda S, Do Nascimento RR, Ximenes EC, Sant’Ana AE (2009) Antimicrobial activities of components of the glandular secretions of leaf cutting ants of the genus Atta. Antonie Van Leeuwenhoek 95:295–303
Micheau O, Lens S, Gaide O, Alevizopoulos K, Tschopp J (2001) NF-kappaB signals induce the expression of c-FLIP. Mol Cell Biol 21:5299–5305
Rayet B, Gelinas C (1999) Aberrant rel/nfkb genes and activity in human cancer. Oncogene 18:6938–6947
Vallabhapurapu S, Karin M (2009) Regulation and function of NF-kappaB transcription factors in the immune system. Annu Rev Immunol 27:693–733
Wang CY, Mayo MW, Korneluk RG, Goeddel DV, Baldwin AS, Jr. (1998) NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 281:1680–1683
Zhu BS, Xing CG, Lin F, Fan XQ, Zhao K, Qin ZH (2011) Blocking NF-kappaB nuclear translocation leads to p53-related autophagy activation and cell apoptosis. World J Gastroenterol 17:478–487
Acknowledgments
We thank Dr Lixin Zhu for her help in English writing and technical supporting and Dr Saijuan Chen for her kindly supply of human tumor cell lines NB4. This experiment was supported by the national science foundation of PR China.
Author information
Authors and Affiliations
Corresponding author
Additional information
Hailong Xia, Wei Liang, and Qin Song contribute equally to this paper.
Rights and permissions
About this article
Cite this article
Xia, H., Liang, W., Song, Q. et al. The in vitro study of apoptosis in NB4 cell induced by citral. Cytotechnology 65, 49–57 (2013). https://doi.org/10.1007/s10616-012-9453-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10616-012-9453-2