European Journal of Nutrition

, Volume 51, Issue 1, pp 39–46 | Cite as

The citrus flavonoid hesperidin induces p53 and inhibits NF-κB activation in order to trigger apoptosis in NALM-6 cells: involvement of PPARγ-dependent mechanism

  • Asghar Ghorbani
  • Maryam Nazari
  • Mahmood Jeddi-Tehrani
  • Hamid ZandEmail author
Original Contribution



Hesperidin, a flavanone present in citrus fruits, has been identified as a potent anticancer agent because of its proapoptotic and antiproliferative characteristics in some tumor cells. However, the precise mechanisms of action are not entirely understood.


The main purpose of this study is to investigate the involvement of peroxisome proliferator-activated receptor-gamma (PPARγ) in hesperidin’s anticancer actions in human pre-B NALM-6 cells, which expresses wild-type p53.


The effects of hesperidin on cell-cycle distribution, proliferation, and caspase-mediated apoptosis were examined in NALM-6 cells in the presence or absence of GW9662. The expression of peroxisome proliferator-activated receptor-gamma (PPARγ), p53, phospho-IκB, Bcl-2, Bax, and XIAP proteins were focused on using the immunoblotting assay. The transcriptional activities of PPARγ and nuclear factor-kappaB (NF-κB) were analyzed by the transcription factor assay kits. The expression of PPARγ and p53 was analyzed using the RT-PCR method.


Hesperidin induced the expression and transcriptional activity of PPARγ and promoted p53 accumulation and downregulated constitutive NF-κB activity in a PPARγ-dependent and PPARγ-independent manner. The growth-inhibitory effect of hesperidin was partially reduced when the cells preincubated with PPARγ antagonist prior to the exposure to hesperidin.


The findings of this study clearly demonstrate that hesperidin-mediated proapoptotic and antiproliferative actions are regulated via both PPARγ-dependent and PPARγ-independent pathways in NALM-6 cells. These data provide the first evidence that hesperidin could be developed as an agent against hematopoietic malignancies.


Hesperidin PPAR-gamma p53 Ikappa B NF-kappaB 



This article is based in part on a thesis made possible by Master research grants from National Institute of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Asghar Ghorbani
    • 1
  • Maryam Nazari
    • 1
  • Mahmood Jeddi-Tehrani
    • 2
  • Hamid Zand
    • 1
    Email author
  1. 1.National Institute and Faculty of Nutrition and Food Technology, Department of Basic Medical SciencesShahid Beheshti University of Medical SciencesTehranIran
  2. 2.Monoclonal Antibody Research Center, Avicenna Research Institute, ACECRTehranIran

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