Abstract
Etoposide (VP-16, Figure 1), a semisynthetic derivative of phodophyllotoxin, is clinically active as a single agent and in combination with other antitumor drugs, e.g. adriamycin and cis-platinum. VP-16 has shown promising activity in the treatment of small cell lung carcinoma, testicular tumors and malignant lymphomas1, 2. VP-16 has been shown to induce DNA strand breaks in tumor cells and it is believed that topoisomerase II is the likely intracellular target for this DNA damage3, 4. Although the DNA strand breaking activity of VP-16 has been implicated in its cytotoxicty, the molecular mechanism remains to be defined. For DNA damage and the biological activity, the presence of cellular components and the presence of free hydroxyl group in the C-4′ are essential5 suggesting other factors may also be important in the biochemical mechanism of the drug.
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