Etoposide's binding prevents topoisomerase II from re-ligating the broken DNA strands, which causes the DNA breaks made by topoisomerase II to stay broken, and also prevents the topoisomerase II molecule from leaving the site and relieving tension elsewhere. This results in a double-strand break in the DNA that can have various deleterious effects on the cell, and depletion of topoisomerase II available to relieve further tension. Cancer cells rely on this enzyme more than healthy cells, since they divide more rapidly. Therefore, this causes errors in DNA synthesis and promotes apoptosis of the cancer cell. Chemistry Etoposide is a semisynthetic derivative of podophyllotoxin from the rhizome of the wild mandrake (Podophyllum peltatum). More specifically, it is a glycoside of podophyllotoxin with a D-glucose derivative. It is chemically similar to the anti-cancer drug teniposide, being distinguished only by a methyl group where teniposide has a thienyl. Both these compounds have been developed with the aim of creating less toxic derivatives of podophyllotoxin. The substance is a white to yellow-brown, crystalline powder. It is soluble in organic solvents. It is used in form of its salt etoposide phosphate. History Etoposide was first synthesized in 1966 and U.S. Food and Drug Administration approval was granted in 1983. The nickname VP-16 likely comes from a compounding of the last name of one of the chemists who performed early work on the drug (von Wartburg) and podophyllotoxin. Another scientist who was integral in the development of podophyllotoxin-based chemotherapeutics was the medical pharmacologist Hartmann F. Stähelin. References External links Benzodioxoles Cancer treatments Furonaphthodioxoles Hepatotoxins IARC Group 1 carcinogens Lactones Phenol ethers Topoisomerase inhibitors World Health Organization essential medicines Wikipedia medicine articles ready to translate