Original Contribution

European Journal of Nutrition

, Volume 51, Issue 1, pp 39-46

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 GhorbaniAffiliated withNational Institute and Faculty of Nutrition and Food Technology, Department of Basic Medical Sciences, Shahid Beheshti University of Medical Sciences
  • , Maryam NazariAffiliated withNational Institute and Faculty of Nutrition and Food Technology, Department of Basic Medical Sciences, Shahid Beheshti University of Medical Sciences
  • , Mahmood Jeddi-TehraniAffiliated withMonoclonal Antibody Research Center, Avicenna Research Institute, ACECR
  • , Hamid ZandAffiliated withNational Institute and Faculty of Nutrition and Food Technology, Department of Basic Medical Sciences, Shahid Beheshti University of Medical Sciences Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Background

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.

Aim

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords

Hesperidin PPAR-gamma p53 Ikappa B NF-kappaB