Accession Number:
ADA463697
Title:
Examination of Potential Anti-Tumor Activity of N-Thiolated b-Lactam Antibiotics in Nude Mice Bearing Human Breast Tumors
Descriptive Note:
Final rept. 30 Jul 2004-29 Jul 2006
Corporate Author:
WAYNE STATE UNIV DETROIT MI
Personal Author(s):
Report Date:
2006-08-01
Pagination or Media Count:
136.0
Abstract:
Activation of the cellular apoptotic program is a current strategy for the prevention and treatment of human cancer including breast cancer. Because of the ease of synthesis and structural manipulation, small molecules with apoptosis-inducing ability have great potential to be developed into chemotherapeutic drugs. The beta-lactam antibiotics have for the past 60 years played an essential role in treating bacterial infections without causing toxic side effects in the host. We hypothesized that active N-thiolated beta-lactams can damage DNA and induce apoptosis in human breast cancer cells in nude mice. In this final report. we have first evaluated potencies of many novel synthetic beta-lactams to inhibit proliferation and induce apoptosis in human cancer cell. We then determined whether several of these beta-lactam, L1, HY2, HY14, HY15 and SC4, could damage breast tumor cell DNA and inhibit breast tumor growth in vivo. We have found that these beta-lactams inhibited growth of implanted MDA-MB-231 breast tumors in a concentration-dependent manner, associated with their DNA-damaging activities. Our studies have provided strong support for proof-of-concept of the potential use of these N-thiolated beta-lactams in breast cancer prevention and treatment.
Descriptors:
Subject Categories:
- Biochemistry
- Medicine and Medical Research
- Toxicology