title: Curcumin inhibits anchorage-independent growth of HT29 human colon cancer cells by targeting epigenetic restoration of the tumor suppressor gene DLEC1.
abstract: 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.
authors: Graduate Program in Pharmaceutical Sciences, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Room 228, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA.
authors: Yue
authors: Y
authors: Guo
authors: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Room 228, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA.
authors: Limin
authors: L
authors: Shu
authors: Graduate Program in Pharmaceutical Sciences, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Room 228, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA.
authors: Chengyue
authors: C
authors: Zhang
authors: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Room 228, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA.
authors: Zheng-Yuan
authors: ZY
authors: Su
authors: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Room 228, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA. Electronic address: kongt@pharmacy.rutgers.edu.
authors: Ah-Ng Tony
authors: AN
authors: Kong
mesh_terms: D001483:Base Sequence; D002448:Cell Adhesion / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D003474:Curcumin / Q000494:pharmacology*; D019175:DNA Methylation; D017931:DNA Primers; D016147:Genes, Tumor Suppressor; D019073:HT29 Cells; D006801:Humans; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C119064:DLEC1 protein, human; D017931:DNA Primers; D025521:Tumor Suppressor Proteins; D003474:Curcumin
keywords: Anchorage-independent growth; Colorectal cancer; Curcumin; DLEC1; Epigenetics
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