[Cytotoxic mechanism and antineoplastic action of etoposide]

Etoposide differs from its parent podophyllotoxin--classical spindle poison; unlike this compound etoposide delays progression of the cell cycle through the late S or early G2 phase. Etoposide inhibits uptake and incorporation of nucleosides into tumour cells but at the concentrations higher than those which are cytotoxic. Single- and double-strand breaks caused by etoposide in cellular DNA are generally considered as the initial event which leads to cell death; the DNA strand breaks result from stabilization of the cleavable complex of topoisomerase II DNA with DNA by etoposide. On the other hand metabolites of etoposide are also likely to exert cytotoxic action. Finally, etoposide has been shown to induce apoptosis, active, energy-dependent process of cellular self-destruction, in human tumour cells.