title: Antitumor activity and induction of apoptosis by water-soluble derivatives of 7 beta-hydroxycholesterol in human colon carcinoma cell lines.
abstract: At present, cancer therapy of solid tumors, such as lung and colorectal cancer, is unsatisfactory. Recently, oxygenated sterols have shown selective cytotoxicity against tumor cells. In this study, the cytotoxicity of 7 beta-hydroxycholesterol (7 beta HC) and two water-soluble derivatives of 7 beta HC, i.e. 7 beta HC-bis-hemisuccinate [disodium salt] (7 beta HC-HS) and 7 beta HC-bis-hemisuccinate-diethanolaminoate (7 beta HC-EA), was determined in DLD-1, KM20L2, HCT-116, HT-29 and SW620 colon carcinoma cell lines using a cell count assay. IC50 values of the two water-soluble derivatives were, on the whole, comparable to 7 beta HC lying in the range of 3-10 microM. In addition, the water-soluble derivatives were able to induce apoptosis in the examined DLD-1 and KM20L2 colon carcinoma cell lines in contrast to the parent compound 7 beta HC, as shown by DNA fragmentation, by the cleavage of DNA repair enzyme poly(ADP) ribose polymerase (PARP), and by the proteolytic cleavage of caspase-3 (CPP32). Due to the improved water-solubility of 7 beta HC-HS and 7 beta HC-EA and their promising antitumor activity in vitro, animal studies in suitable tumor models are warranted.
authors.affiliation: Tumor Biology Center, Dept. of Medical Oncology, Freiburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Maier
authors.forename: G
authors.initials: G
authors.lastname: Bing
authors.forename: U
authors.initials: U
authors.lastname: Falken
authors.forename: E
authors.initials: E
authors.lastname: Wagner
authors.forename: C
authors.initials: C
authors.lastname: Unger
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D002458:Cell Fractionation; D003110:Colonic Neoplasms / Q000473:pathology*; D053938:DNA Fragmentation; D018922:HL-60 Cells; D006801:Humans; D006888:Hydroxycholesterols / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: C403964:7 beta-hydroxycholesterol-bis-hemisuccinate-diethanolaminoate; C041101:7-hydroxycholesterol-3,7-bis(hemisuccinate); D000970:Antineoplastic Agents; D006888:Hydroxycholesterols; C011724:cholest-5-en-3 beta,7 alpha-diol