The comparison of cytotoxicity of the anticancer drugs doxorubicin and ellipticine to human neuroblastoma cells
Ellipticine is an antineoplastic agent, whose mode of action is based mainly on DNA intercalation, inhibition of topoisomerase II and formation of covalent DNA adducts mediated by cytochromes P450 and peroxidases. Here, the cytotoxicity of ellipticine to human neuroblastoma derived cell lines IMR-32 and UKF-NB-4 was investigated. Treatment of neuroblastoma cells with ellipticine was compared with that of these cancer cells with doxorubicin. The toxicity of ellipticine was essentially the same as that of doxorubicin to UKF-NB-4 cells, but doxorubicin is much more effective to inhibit the growth of the IMR-32 cell line than ellipticine. Hypoxic conditions used for the cell cultivation resulted in a decrease in ellipticine and/or doxorubicin toxicity to IMR-32 and UKF-NB-4 neuroblastoma cells.
Auclair C (1987) Multimodal action of antitumor agents on DNA: The ellipticine series. Arch Biochem Biophys259: 1-14.
Bedrníček J, Vícha A, Jarošová M, Holzerová M, Činátl J Jr, Michaelis M, Činátl J, Eckschlager T (2005) Characterization of drug-resistant neuroblastoma cell lines by comparative genomic hybridization. Neoplasma52: 415-419.
Borek-Dohalská L, Frei E, Stiborová M (2004) DNA adduct formation by the anticancer drug ellipticine and its hydroxy derivatives in human breast adenocarcinoma MCF-7 cells. Collect Czech Chem Commun69: 603-615.
Brodeur GM (2003) Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer3: 203-216.
Frei E, Bieler CA, Arlt VM, Wiessler M, Stiborová M (2002) Covalent binding of the anticancer drug ellipticine to DNA in V79 cells transfected with human cytochrome P450 enzymes. Biochem Pharmacol64: 289-295.
Hardesty CT, Chaney NA, Mead JA (1972) The effect of route of administration on the distribution of ellipticine in mice. Cancer Res32: 1884-1889.
Kotchetkov R, Cinatl J, Blaheta R, Vogel JU, Karaskova J, Squire J, Hernáiz Driever P, Klingebiel T, Cinatl J Jr (2003) Development of resistance to vincristine and doxorubicin in neuroblastoma alters malignant properties and induces additional karyotype changes: a preclinical model. Int J Cancer104: 36-43.
Lesca P, Beaune P, Monsarrat B (1981) Ellipticines and human liver microsomes: spectral interaction with cytochrome P-450 and hydroxylation. Inhibition of arylhydrocarbon metabolism and mutagenicity. Chem-Biol Interact36: 299-309.
Maris JM, Mathay KK (1999) Molecular biology of neuroblastomas. J Clin Oncol17: 2264-2279.
Murray GI, Weaver RJ, Paterson PJ, Ewen SW, Melvin WT, Burke MD (1993) Expression of xenobiotic metabolizing enzymes in breast cancer. J Pathol169: 347-353.
Stiborová M, Bieler CA, Wiessler M, Frei E (2001) The anticancer agent ellipticine on activation by cytochrome P450 forms covalent DNA adducts. Biochem Pharmacol62: 1675-1684.
Stiborová M, Stiborová-Rupertová M, Bořek-Dohalská L, Wiessler M, Frei E (2003a) Rat microsomes activating the anticancer drug ellipticine to species covalently binding to deoxyguanosine in DNA are a suitable model mimicking ellipticine bioactivation in humans. Chem Res Toxicol16: 38-47.
Stiborová M, Breuer A, Aimová D, Stiborová-Rupertová M, Wiessler M, Frei E (2003b) DNA adduct formation by the anticancer drug ellipticine in rats determined by 32P-postlabeling. Int J Cancer107: 885-890.