Examination pf Potential Anti-Tumor Activity of N-Thiolated B-Lactam Antibiotics in Nude Mice Bearing Human Breast Tumors
Annual rept. 30 Jul 2004-29 Jul 2005
WAYNE STATE UNIV DETROIT MI
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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 b-lactams can damage DNA and induce apoptosis in human breast cancer cells in nude mice. In this summary report, we have first evaluated potencies of several novel synthetic beta-lactams to inhibit proliferation and induce apoptosis in human cancer cells. We then determined whether one of these b-lactams, HY14, could inhibit breast tumor growth in vivo. We have found that HY14 inhibited growth of implanted MDA-MB-231 breast tumors in a concentrationdependent manner, associated with its DNA-damaging activity. We are currently testing more novel beta-lactams in nude mice bearing human breast tumors. Our studies have provided strong support for proof-of-concept of the potential use of these Nthiolated beta-lactams in breast cancer prevention and treatment.
- Medicine and Medical Research