Cytotoxic Antiestrogens for Breast Cancer
Abstract
This project examined a new agent that combines a transition metal anticancer agent CDDP with an antiestrogen (tamoxifen analogs) in the breast and ovarian cancer cell lines. The tamoxifen portion of the conjugate would serve as a carrier to selectively accumulate CDDP portion in the nucleus of ER-positive cancer cells, while CDDP alone does not show any selectivity between normal and cancer cells. The combined agent would result in selective accumulation in estrogen receptor (ER) positive cancer cells and also produce a cytotoxic effect by the reaction of CDDP with DNA. Synergistic inhibition of human cancer cell growth by CDDP and tamoxifen on an intermolecular basis has been demonstrated in vivo. The uniqueness of the present proposal is the covalent linkage between tamoxifen and platinum, which could be cleaved either enzymatically or chemically. A number of conjugates have been synthesized and characterized. All conjugates show cytotoxicity. A conjugate with greater potency than carboplatin has been observed. However, the potency does not correlate with estrogen receptor binding affinity well. No synergistic effect among the fragments of conjugates has been observed.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2002
- Accession Number
- ADA405447
Entities
People
- Lislisheng Cai
Organizations
- University of Illinois at Chicago