title: Curcumin induces apoptosis in human colorectal carcinoma (HCT-15) cells by regulating expression of Prp4 and p53.
abstract: Curcumin (diferuloylmethane), the yellow pigment of turmeric, is one of the most commonly used and extensively studied phytochemicals due to its pleiotropic effects in several human cancers. In the current study, the therapeutic efficacy of curcumin was investigated in human colorectal carcinoma HCT-15 cells. Curcumin inhibited HCT-15 cells proliferation and induced apoptosis in a dose- and time-dependent manner. Hoechst 33342 and DCFHDA staining revealed morphological and biochemical features of apoptosis as well as ROS generation in HCT-15 cells treated with 30 and 50 μM curcumin. Over-expression of pre-mRNA processing factor 4B (Prp4B) and p53 mutations have been reported as hallmarks of cancer cells. Western blot analysis revealed that curcumin treatment activated caspase-3 and decreased expression of p53 and Prp4B in a time-dependent manner. Transfection of HCT-15 cells with Prp4B clone perturbed the growth inhibition induced by 30 μM curcumin. Fractionation of cells revealed increased accumulation of Prp4B in the nucleus, following its translocation from the cytoplasm. To further evaluate the underlying mechanism and survival effect of Prp4B, we generated siRNA-Prp4B HCT15 clones. Knockdown of Prp4B with siRNA diminished the protective effects of Prp4B against curcumin-induced apoptosis. These results suggest a possible underlying molecular mechanism in which Prp4B over-expression and activity are closely associated with the survival and regulation of apoptotic events in human colon cancer HCT-15 cells.
authors.affiliation: School of Life Sciences, College of Natural Sciences, Kyungpook National University, Daegu 700-721, Korea.
authors.forename: Adeeb
authors.initials: A
authors.lastname: Shehzad
authors.forename: Jaetae
authors.initials: J
authors.lastname: Lee
authors.forename: Tae-Lin
authors.initials: TL
authors.lastname: Huh
authors.forename: Young Sup
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D048708:Cell Growth Processes / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D003474:Curcumin / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009154:Mutation / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D017414:Ribonucleoprotein, U4-U6 Small Nuclear / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D017414:Ribonucleoprotein, U4-U6 Small Nuclear; D016159:Tumor Suppressor Protein p53; C489984:PRPF4B protein, human; D017346:Protein Serine-Threonine Kinases; D053148:Caspase 3; D003474:Curcumin