title: Inhibitory effects of cholesterol derivatives on DNA polymerase and topoisomerase activities, and human cancer cell growth.
abstract: This paper describes the inhibitory activities of cholesterol derivatives such as cholesterol, sodium cholesteryl sulfate, cholesteryl-5alpha, 6alpha-epoxide, cholesteryl chloride, cholesteryl bromide, and cholesteryl hemisuccinate (compounds 1-6, respectively) against DNA polymerase (pol), DNA topoisomerase (topo), and human cancer cell growth. Among the compounds tested, compounds 2 and 6 revealed themselves to be potent inhibitors of animal pols, and the IC50 values for pols were 0.84-11.6 and 2.9-148 microM, respectively. Compounds 2, 3 and 6 inhibited the activity of human topo II, with IC50 values of 5.0, 12.5 and 120 microM, respectively. Compounds 2, 3 and 6 also suppressed human cancer cell (promyelocytic leukemia cell line, HL-60) growth, and LD50 values were 8.8, 20.2 and 72.3 microM, respectively, suggesting that cell growth inhibition had the same tendency as the inhibition of topos rather than pols. Compounds 2 and 6 arrested the cells in S and G2/M phases, compound 3 arrested the cells in the G2/M phase, and these compounds also increased sub-G1 phase in the cell cycle. These results suggested that the effect of cell cycle arrest might be effective on both pols and topos activities. From these findings, the action mode of cholesterol derivatives as anti-cancer compounds is discussed.
authors.affiliation: Laboratory of Food & Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Kobe, Hyogo 651-2180, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Ishimaru
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yonezawa
authors.forename: Isoko
authors.initials: I
authors.lastname: Kuriyama
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nishida
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mizushina
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle; D049109:Cell Proliferation; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D026942:DNA Topoisomerases / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D019384:Nucleic Acid Synthesis Inhibitors; D059003:Topoisomerase Inhibitors
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D059003:Topoisomerase Inhibitors; D002784:Cholesterol; D004259:DNA-Directed DNA Polymerase; D026942:DNA Topoisomerases