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.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
M. Rozencweig, D. D. Von Hoff, J. E. Henney, and F. M. Muggia, VM-26 and VP-16–213: a comparative analysis, Cancer 40: 334 (1977).
P.J. Dwyer, B. Leyland-Jones, M. T. Alonso, S. Marsoni, and R.E. Wittes, Etoposide (VP-16–213): current status of an active anticancer drug, N. Engl. J. Med., 312: 692 (1985).
A. J. Wojniac, and W. E. Ross, DNA damage as a basis for 4′-demethylepipodophyllotoxin-9-(4,6-O-ethylene-β-D-glucopyranoside (etoposide) cytotoxicity, Cancer Res., 43: 120 (1983) .
B. H. Long, S. T. Musial, and M. G. Brattain, Comparison of cytotoxicity and DNA breakage activity of congeners of podophyllotoxin including VP-16–213 and VM-26: a quantative structure-activity relationship, Biochemistry, 23: 1183 (1984).
J. D. Loike, and S. B. Horwitz, Effects of VP-16–213 on the intracellular degradation of DNA in HeLa cells, Biochemistry 15: 5443 (1976).
N. Haim, J. Nemec, J. Roman, and B. K. Sinha, In vitro metabolism of etoposide (VP-16–213) by liver microsomes and irreversible binding of reactive intermediates to microsomal proteins, Biochem. Pharmacol., 36: 527 (1987).
B. K. Sinha, and C. E. Myers, Irreversible binding of etoposide (VP-16–213) to deoxyribonucleic acid and proteins, Biochem. Pharmacol., 33 : 3725 (1984).
B. K. Sinha, M. A. Trush, and B. Kalayanaraman, Microsomal interactions and inhibition of lipid peroxidation by etoposide (VP-16–213): Implications for mode of action, Biochem. Pharmacol., 34: 2036 (1985).
B. K. Sinha, M. A. Trush, and B. Kalayanaraman, Free radical metabolism of VP-16 and inhibition of anthracycline-induced lipid peroxidation, Biochem. Pharmacol., 32: 3495 (1983).
N. Haim, J. Roman, J. Nemec, and B. K. Sinha, Peroxidative free radical formation and O-demethylation of etoposide (VP-16) and teniposide (VM-26), Biochem. Biophys. Res. Commun., 135: 215 (1986).
A. G. Katki, B. Kalayanaraman, and B. K. Sinha, Interactions of the antitumor drug, etoposide, with reduced thiols in vitro and in vivo, Chem. Biol. Interact., 62, 237 (1987).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1988 Plenum Press, New York
About this chapter
Cite this chapter
Sinha, B.K. (1988). Role of Free Radicals in Etoposide (Vp-16,213) Action. In: Simic, M.G., Taylor, K.A., Ward, J.F., von Sonntag, C. (eds) Oxygen Radicals in Biology and Medicine. Basic Life Sciences, vol 49. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5568-7_121
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5568-7_121
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5570-0
Online ISBN: 978-1-4684-5568-7
eBook Packages: Springer Book Archive