Inhibitory effects of cholesterol derivatives on DNA polymerase and topoisomerase activities, and human cancer cell growth.

Lipids
Chisato IshimaruY Mizushina

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 actio...Continue Reading

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Citations

Jun 9, 2009·Bioscience, Biotechnology, and Biochemistry·Yoshiyuki Mizushina
Feb 19, 2009·Bioorganic & Medicinal Chemistry·Takuma KimuraYoshiyuki Mizushina
Oct 28, 2008·Bioorganic & Medicinal Chemistry·David Díaz-CarballoH Peter Reusch
May 23, 2012·Biochimie·Marc Poirot, Sandrine Silvente-Poirot
Apr 4, 2015·BioMed Research International·Jaleh VarshosazMahboobeh Rostami
Aug 25, 2012·Current Opinion in Pharmacology·Sandrine Silvente-Poirot, Marc Poirot
Feb 5, 2014·Saudi Pharmaceutical Journal : SPJ : the Official Publication of the Saudi Pharmaceutical Society·Awwad A Radwan, Fares K Alanazi
Nov 16, 2012·Natural Product Reports·Jorge A R SalvadorM Luisa Sá e Melo
Jan 30, 2019·Cancers·Fahim AhmadJayne M Stommel
May 5, 2011·International Journal of Molecular Sciences·Yoshiyuki MizushinaMasaru Yoshida
Jan 24, 2020·World Journal of Clinical Cases·Hao Liu, Shuai Huang
Oct 12, 2010·Journal of Medicinal Chemistry·João F S CarvalhoM Luisa Sá e Melo

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