Synthetic Beta-Lactam Antibiotics as a Selective Breast Cancer Cell Apoptosis Inducer: Significance in Breast Cancer Prevention and Treatment
Annual rept. 1 Mar 2006-28 Feb 2007
WAYNE STATE UNIV DETROIT MI
Pagination or Media Count:
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 b-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 target a tumor-specific proteins and selectively induce apoptosis in human breast cancer but not normal cells. In this report, we have designed and synthesized a number of beta-lactams with selected C3 and C4 ring substituents, and evaluated their potencies to inhibit proliferation and induce apoptosis in human breast cancer, but not normal cells. We have also studied the biochemical targets of these b-lactams by synthesizing and using labeled compounds as well as by performing microarray assay. Our results supported by this IDEA award and the Concept Award strongly support our hypothesis that beta-lactams cause tumor DNA damage, which is responsible for their anti-tumor activities. Our studies have provided strong support for proof-of-concept of the potential use of these b-lactams in breast cancer prevention and treatment.
- Medicine and Medical Research