BIOCHEMICAL MECHANISMS OF ETOPOSIDE; UPSHOT OF CELL DEATH

Etoposide is an antineoplastic agent employed for healingvarious malignancies in human. It is a semi-synthetic derivative of podophyllotoxin and was introduced in 1971. The primary mode of action of etoposide is the inhibition of the function of the enzyme topoisomerase II. It stabilizes DNA-enzyme complex, and accumulation of this complex enhances the probability of double-stranded DNA breaks. However, etoposide can also causes DNA lesions in cancerous cells. This genotoxicity and antineoplastic activity of drug at the same time serve as the impetus for intensive research. Etoposide treatment causes permanent DNA breaks pertaining to its significant role in cell death and growth arrest in tumor cells. This review attempts to provide the deep knowledge of its possible biochemical pathways which are triggered in response to DNA breaks and leads to apoptosis and cell cycle arrest as well transcriptional activation of various death receptors. Molecular mechanism of drug efflux and activation of repairing proteins which can cause resistance in its action are also discussed. This current picture of known facts serve as a gateway to design more effective and efficient antitumor drugs, with new therapeutic strategies, combinations and modulation followed by the visualization of its biochemical mechanisms