title: Ellagic acid inhibits proliferation and induced apoptosis via the Akt signaling pathway in HCT-15 colon adenocarcinoma cells.
abstract: Chemoprevention is regarded as one of the most promising and realistic approaches in the prevention of human cancer. Ellagic acid (EA) has been known for its chemopreventive activity against various cancers and numerous investigations have shown its apoptotic activity both in vivo and in vitro. The present study was focused to elucidate the anticancerous effect and the mode of action of EA against HCT-15 colon adenocarcinoma cells. Cell viability was assessed using trypan blue assay at different concentrations. EA also promoted cell cycle arrest substantially at G2/M phase in HCT-15 cells. The activities of alkaline phosphatase and lactate dehydrogenase were decreased upon EA treatment, which shows the antiproliferative and the cytotoxic effects, respectively. The production of reactive oxygen intermediates, which were examined by 2,7-dichlorodihydrofluorescein diacetate (H2DCF-DA), increased with time, after treatment with EA. In further studies, EA inhibited proliferation-associated markers proliferating cell nuclear antigen and cyclin D1. The induction of apoptosis was accompanied by a strong inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway by EA. The expression of PI3K and pAkt was down-regulated in EA-treated cells, compared to normal cells. Further, EA promoted the expression of Bax, caspase-3, and cytochrome c, and suppression of Bcl-2 activity in HCT-15 cells that was determined by western blot analysis. Increased annexin V apoptotic cells and DNA fragmentation also accompanied EA-induced apoptosis. In conclusion, EA increased the production of ROS, decreased cell proliferation, and induced apoptosis in HCT-15 cells, and thus can be used as an agent against colon cancer.
authors.affiliation: Department of Biochemistry, Cell Biology Unit, University of Madras, Maraimalai Campus (Guindy), Chennai, 600 025, Tamil Nadu, India, umesalmas@gmail.com.
authors.forename: Syed
authors.initials: S
authors.lastname: Umesalma
authors.forename: Ponnuraj
authors.initials: P
authors.lastname: Nagendraprabhu
authors.forename: Ganapasam
authors.initials: G
authors.lastname: Sudhandiran
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000469:Alkaline Phosphatase / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D048430:Cell Shape; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy; D019938:Cyclin D1 / Q000378:metabolism; D053938:DNA Fragmentation; D004354:Drug Screening Assays, Antitumor; D004610:Ellagic Acid / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; C530104:CCND1 protein, human; D018809:Proliferating Cell Nuclear Antigen; D019938:Cyclin D1; D004610:Ellagic Acid; D007770:L-Lactate Dehydrogenase; D051057:Proto-Oncogene Proteins c-akt; D000469:Alkaline Phosphatase