A DNA-intercalating antitumor agent
Ellipticine is an alkaloid isolated from Apocyanaceae plants that exhibits antitumor activities by intercalating into DNA and/or inhibiting DNA topoisomerase II.1,2,3 It forms covalent adducts in DNA after being enzymatically activated with cytochrome P450 isoforms (e.g., CYP3A4, CYP1A1, or CYP1A2) or by peroxidases in target tissues.2,3 Ellipticine has been shown to inhibit the proliferation of human breast adenocarcinoma MCF-7 cells, leukemia HL-60 and CCRF-CEM cells, neuroblastoma IMR-32, UKF-NB-3, and UKF-NB-4 cells, and U87MG glioblastoma cells with IC50 values ranging from 0.27-4.7 ?M.2
1.Kohn, K.W., Waring, M.J., Glaubiger, D., et al.Intercalative binding of ellipticine to DNACancer Res.35(1)71-76(1975) 2.Stiborová, M., Poljakova, J., Martinkova, E., et al.Ellipticine cytotoxicity to cancer cell lines - a comparative studyInterdiscip. Toxicol.4(2)98-105(2011) 3.Aimová, D., Svobodová, L., Kotrbová, V., et al.The anticancer drug ellipticine is a potent inducer of rat cytochromes P450 1A1 and 1A2, thereby modulating its own metabolismDrug Metab. Dispos.35(10)1926-1934(2007)
Cell experiment: | The cytotoxicity of Ellipticine (NSC 71795) is determined by MTT test. Ellipticine (NSC 71795) is dissolved in DMSO (1 mM) and diluted in culture medium to final concentrations of 0, 0.1, 1, 5 or 10 μM. Cells in exponential growth are seeded at 1×104 per well in a 96-well microplate. After incubation the MTT solution is added, the microplates are incubated for 4 hours and cells lysed in 50% N,N-dimethylformamide containing 20% of sodium dodecyl sulfate (SDS), pH 4.5. The absorbance at 570 nm is measured. The mean absorbance of medium controls is subtracted as a background. The viability of control cells is taken as 100% and the values of treated cells are calculated as a percentage of control. The IC50 values are calculated using linear regression of the dose-log response curves[2]. |
参考文献: [1]. Stiborova M, et al. Molecular mechanisms of antineoplastic action of an anticancer drug ellipticine. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2006 Jul;150(1):13-23. | |
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