Tyrosinase-induced free radical formation from VP-16,213: relationship to cytotoxicity.

Abstract

Tyrosinase-dependent activation of hydroxybenzenes forms reactive compounds, including catechols and o-quinones, and some of which show antitumor activity against pigmented melanomas. Since VP-16 is a phenoxy-containing antitumor drug, forms free radicals and reactive o-quinones during peroxidative activation, we evaluated the cytotoxicity of VP-16 to both tyrosinase-containing and non-tyrosinase-containing tumor cells. Our results show that VP-16 is significantly more cytotoxic to B-16/F-10 melanoma cells than human MCF-7 breast tumor cells. Phenylthiocarbamide, an inhibitor of tyrosinase activity, selectively decreased VP-16 toxicity only in melanoma cells. Furthermore, VP-16 was readily activated to its phenoxy free radical intermediate by purified tyrosinase, indicating tyrosinase may play a role in VP-16 toxicity in pigmented melanomas.

• Authors: N Usui, B K Sinha
• Journal: Free radical research communications (Free Radic Res Commun) Vol. 10 Issue 4-5 Pg. 287-93 ( 1990) ISSN: 8755-0199 [Print] Switzerland
• PMID: 1963166 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Free Radicals
• Phenylthiourea
• Etoposide
• Monophenol Monooxygenase

Topics

• Animals
• Breast Neoplasms (drug therapy, enzymology)
• Electron Spin Resonance Spectroscopy
• Etoposide (metabolism, therapeutic use)
• Free Radicals
• Humans
• Melanoma, Experimental (drug therapy, enzymology)
• Mice
• Monophenol Monooxygenase (antagonists & inhibitors, metabolism)
• Phenylthiourea (pharmacology)
• Tumor Cells, Cultured