etoposide brands

Molecular formula: C29H32O13

Etoposide inhibits DNA topoisomerase II, thereby inhibiting DNA re-ligation. This causes critical errors in DNA synthesis at the premitotic stage of cell division and can lead to apoptosis of the cancer cell. Etoposide is cell cycle dependent and phase specific, affecting mainly the S and G2 phases of cell division. Inhibition of the topoisomerase II alpha isoform results in the anti-tumour activity of etoposide. The drug is also capable of inhibiting the beta isoform but inhibition of this target is not associated with the anti-tumour activity. It is instead associated with the carcinogenic effect. The drug appears to produce its cytotoxic effects by damaging DNA and thereby inhibiting or altering DNA synthesis. ... Etoposide appears to be cell-cycle dependent and cycle-phase specific, inducing G2 phase arrest and preferentially filling cells in the G2 and late S phases. Etoposide has been shown to arrest metaphase in chick fibroblasts, but its principal effect in mammalian cells appears to be in the G2 phase. At etoposide concentrations of 0.3-10 ug/ml in vitro, cells are inhibited from entering prophase; at concentrations of 10 ug/ml or higher, lysis of cells entering mitosis occurs. ... Etoposide does not inhibit microtubule assembly. Etoposide has been shown to induce single-stranded DNA breaks in HeLa cells and in murine leukemia L1210 cells in vitro; the drug also induces double-stranded DNA breaks and DNA-protein crosslinks in L1210 cells. Etoposide induced DNA damage appears to correlate well with the cytotoxicity of the drug. ... Etoposide appears to induce single-stranded DNA breaks indirectly, possibly through endonuclease activation, inhibition of intranuclear type II topoisomerase, or formation of a free-radical metabolite via an enzymatic reaction involving the hydroxyl group at the C-4' position of the E ring. Etoposide also reversibly inhibits the facilitated diffusion of nucleosides into HeLa cells in a concentration dependent manner in vitro. Etoposide may stabilize type II topoisomerase DNA complexes, preventing rejoining of single and double strand DNA breaks. Etoposide may also require cellular activation into intermediates, which then bind to DNA and disrupt cellular function.

Source: PubChem (NCBI) · compound 36462