phenylthiourea and Breast-Neoplasms

Topics: Alkaptonuria; Arsenites; Blood Grouping and Crossmatching; Blood Transfusion; Breast Neoplasms; Classification; Cytochrome P-450 Enzyme System; Female; Genetic Testing; Genetic Therapy; Genetics; Genome, Human; Genotype; Greece; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; Human Genome Project; Humans; Medical History Taking; Medicine, Ayurvedic; Pharmacogenetics; Phenylthiourea; Potassium Compounds; Precision Medicine; Sequence Analysis, DNA; Taste; Warfarin

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.

Topics: Animals; Breast Neoplasms; Electron Spin Resonance Spectroscopy; Etoposide; Free Radicals; Humans; Melanoma, Experimental; Mice; Monophenol Monooxygenase; Phenylthiourea; Tumor Cells, Cultured