title: C2-ceramide exhibits antiproliferative activity and potently induces apoptosis in endometrial carcinoma.
abstract: The purpose of the present study was to investigate the effects of an exogenously administered cell-permeable synthetic ceramide analogue, C(2)-ceramide (N-acetyl-sphingosine) on the growth, cell cycle, and death of Ishikawa human endometrial carcinoma cells. We investigated the effects of C(2)-ceramide on Ishikawa endometrial cancer cell lines in vitro. The cells were treated with C(2)-ceramide, and its effects on cell growth, cell cycle, apoptosis, and related measurements were investigated. MTT assays showed that C(2)-ceramide, a cell-permeable analogue of ceramide, significantly induced dose- and time-dependent death in human endometrial carcinoma Ishikawa cells. Cell-cycle analysis indicated that their exposure to C(2)-ceramide decreased the proportion of cells in S phase and increased the proportion in G0/G1 and/or G2/M phases of the cell cycle. Induction of apoptosis was confirmed by annexin V staining of externalized phosphatidylserine and loss of the transmembrane potential of mitochondria. This induction occurred in concert with the altered expression of genes related to cell growth, malignant phenotype, and apoptosis, including cleavage of poly-ADP ribose polymerase. Furthermore, we demonstrated that the amount of phosphorylated Akt was decreased by C(2)-ceramide. These results raise the possibility that C(2)-ceramide may prove particularly effective in the treatment of endometrial cancers.
authors.affiliation: Department of Obstetrics and Gynecology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593, Japan. takai@med.oita-u.ac.jp
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Takai
authors.forename: Tami
authors.initials: T
authors.lastname: Ueda
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawano
authors.forename: Masakazu
authors.initials: M
authors.lastname: Nishida
authors.forename: Kaei
authors.initials: K
authors.lastname: Nasu
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narahara
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D016889:Endometrial Neoplasms / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D010641:Phenotype; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; C064769:N-acetylsphingosine; D013110:Sphingosine