New Drugs for Prevention of Breast Cancer Metastases
Abstract
This project has as its basis the discovery in my laboratory of a unique drug-responsive and growth-related hydroquinone (NADH) oxidase with protein disulfide-thiol interchange activity at the external cell surface. In metastasis models, tNOX inhibitors have slowed or prevented the invasive spread of cancer. The present project was to develop one or more lead drugs to reduce metastases in mice bearing transplanted mammary carcinomas. Glaucarubolone, a natural product tNOX inhibitor, both free and conjugated to polyethylene-glycol 5000, was prepared in quantities sufficient for animal testing. Free glaucarubolone supplied intra-tumorally was toxic and ineffective in the prevention of the formation of lung metastases. The conjugate was not toxic and a response was seen at the highest concentration tested of 5 mg/injection/mouse. In a collagen invasion assay, the glaucarubolone-PEG conjugate was effective at concentrations between 10(exp -8) and 10(exp -10) M. Green tea catechins were explored as potentially clinically useful redox potentiators of glaucarubolone anticancer activity. A relatively nontoxic mixture of glaucarubolone, epicatechin and epigallocatechin gallate was found to have excellent activity against 4T1 mouse mammary cancer cells and will be explored further as a new tNOX-based therapeutic strategy for management of breast cancer patients.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA376674
Entities
People
- D. J. Morre
Organizations
- Purdue Research Foundation