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Mechanism of action [ edit ] Etoposide forms a ternary complex with DNA and the topoisomerase II enzyme, which is an enzyme that aids in relaxing negative or positive supercoils in DNA.
Etoposide, a semi-synthetic derivative of epipodophyllotoxin is commonly used to study this apoptotic mechanism and include: Etoposide; Teniposide; Both etoposide and teniposide are naturally occurring semi-synthetic derivatives of podophyllotoxins and are important anti-cancer drugs that function to inhibit TopII activity. [67]
Etoposide, an epipodophyllotoxin. Epipodophyllotoxins are substances naturally occurring in the root of American Mayapple plant (Podophyllum peltatum). Some epipodophyllotoxin derivatives are currently used in the treatment of cancer. These include etoposide and teniposide. They act as anti-cancer drugs by inhibiting topoisomerase II. [1]
This is by far the most-accepted mechanism to explain the action of anthracyclines as topoisomerase-II mediated toxicity is evident at clinically relevant drug concentrations. [19] [26] Topoisomerase-II is an enzyme that creates temporary double-stranded DNA (dsDNA) breaks and reseals them after managing torsion of DNA supercoils.
No systematic interaction studies are available. The enzyme inducers phenobarbital and phenytoin have been found to lower its blood plasma concentrations. [4] Theoretically possible interactions include increased plasma concentrations when combined with sodium salicylate, sulfamethizole or tolbutamide, which displace teniposide from plasma protein binding, at least in vitro.
Etoposide: a topoisomerase inhibitor from the group of epipodophyllotoxins; Prednisolone: a glucocorticoid hormone that can cause apoptosis and lysis of both normal and malignant lymphocytes; Oncovin, also known as vincristine: a vinca alkaloid that binds to the protein tubulin, thereby preventing the formation of microtubules and mitosis;
Inside cells, amifostine detoxifies reactive metabolites of platinum and alkylating agents, as well as scavenges free radicals. [1] [2] Other possible effects include accelerated DNA repair, [1] induction of cellular hypoxia, [1] inhibition of apoptosis, [2] alteration of gene expression [2] and modification of enzyme activity. [2]
An Hsp90 inhibitor is a substance that inhibits that activity of the Hsp90 heat shock protein.Since Hsp90 stabilizes a variety of proteins required for survival of cancer cells, these substances may have therapeutic benefit in the treatment of various types of malignancies. [2]
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