A New Class of Membrane Active Drugs for the Treatment of Breast Cancer Cells Transplanted into Athymic Mice.
Abstract
The main objective of this study was to determine the effect of preactivated merocyanine 540 (pM4C540) and merodantoin on the growth of established human MCF-7 breast cancer xenografts and study the toxicity, biodistribution and plasma clearance of merodantoin. Treatment of established tumors with pMC540 and merodantoin resulted in a 74% and 84% inhibition of tumor growth, respectively. Under the conditions of estradiol deprivation, this inhibition was reduced to 42% and 25%, respectively. Combined treatment with either pMC540 or merodantoin plus tamoxifen did not produce a significant enhancement of tumor growth inhibition. The LD50 and LD90 of merodantoin were determined to be 1042 mg/kg and 1250 mg/kg, respectively. The plasma half-life of merodantoin was 25 hours. Organ specific accumulation of medrodantoin was not observed and majority (>70%) of the drug was eliminated via urine and feces. Both pMC540 and merodantoin were found to mediate their cytotoxic effects via initial interaction with topoisomerase II. There is a correlation between DNA topoisomerase II activity and drug-sensitive (MCF-7) and -insensitive (MDA-MB-231) breast cancer cell lines. Breast cancer cells resistant to pMC540 and merodantoin were found to contain undetectable or very low levels of topoisomerase II.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 07, 1994
- Accession Number
- ADA292515
Entities
People
- Kirpal S. Gulliya