Ellipticine

Ellipticine (NSC 71795) is a potent antineoplastic agent; inhibits DNA topoisomerase II activities. In Vitro: Ellipticine (NSC 71795) is a potent antineoplastic agent exhibiting the multimodal mechanism of its action. The mechanisms of Ellipticine (NSC 71795) antitumor, mutagenic and cytotoxic activities are suggested to be intercalation into DNA and inhibition of DNA topoisomerase II activity. Another mode of Ellipticine (NSC 71795) action is the formation of covalent DNA adducts mediated by its oxidation with cytochromes P450 (CYP) and peroxidases^[1]. Ellipticine (NSC 71795) can also act as an inhibitor or inducer of biotransformation enzymes, thereby modulating its own metabolism leading to its genotoxic and pharmacological effects. Treatment of cells with Ellipticine (NSC 71795) results in inhibition of cell growth and proliferation. This effect is associated with formation of two covalent Ellipticine (NSC 71795)-derived DNA adducts^[2]. In Vivo: Ellipticine (NSC 71795) treatment results in Ellipticine (NSC 71795)-derived DNA adduct generation in several healthy organs (liver, kidney, lung, spleen, breast, heart and brain) and in DNA of mammary adenocarcinoma. The levels of Ellipticine (NSC 71795)-derived DNA adducts generated in these adenocarcinomas are almost 2-fold higher than in normal healthy mammary tissue. The induced expression of cytochrome b₅ protein in liver of rats treated with Ellipticine (NSC 71795) suggests that cytochrome b₅ may modulate the CYP-mediated bioactivation and detoxification of Ellipticine (NSC 71795)^[3].