Colorectal cancer remains the most prevalent malignancy in humans. The impact of 
epigenetic alterations on the development of this complex disease is now being 
recognized. The dynamic and reversible nature of epigenetic modifications makes 
them a promising target in colorectal cancer chemoprevention and treatment. 
Curcumin (CUR), the major component in Curcuma longa, has been shown as a potent 
chemopreventive phytochemical that modulates various signaling pathways. Deleted 
in lung and esophageal cancer 1 (DLEC1) is a tumor suppressor gene with reduced 
transcriptional activity and promoter hypermethylation in various cancers, 
including colorectal cancer. In the present study, we aimed to investigate the 
inhibitory role of DLEC1 in anchorage-independent growth of the human colorectal 
adenocarcinoma HT29 cells and epigenetic regulation by CUR. Specifically, we 
found that CUR treatment inhibited colony formation of HT29 cells, whereas 
stable knockdown of DLEC1 using lentiviral short hairpin RNA vector increased 
cell proliferation and colony formation. Knockdown of DLEC1 in HT29 cells 
attenuated the ability of CUR to inhibit anchorage-independent growth. 
Methylation-specific polymerase chain reaction (MSP), bisulfite genomic 
sequencing, and methylated DNA immunoprecipitation revealed that CUR decreased 
CpG methylation of the DLEC1 promoter in HT29 cells after 5 days of treatment, 
corresponding to increased mRNA expression of DLEC1. Furthermore, CUR decreased 
the protein expression of DNA methyltransferases and subtypes of histone 
deacetylases (HDAC4, 5, 6, and 8). Taken together, our results suggest that the 
inhibitory effect of CUR on anchorage-independent growth of HT29 cells could, at 
least in part, involve the epigenetic demethylation and up-regulation of DLEC1.