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.