Accession Number : ADA485735


Title :   Synthetic Beta-Lactam Antibiotics as a Selective Breast Cancer Cell Apoptosis Inducer: Significance in Breast Cancer Prevention and Treatment


Descriptive Note : Annual summary rept. 01 Mar 2004-28 Feb 2008


Corporate Author : WAYNE STATE UNIV DETROIT MI


Personal Author(s) : Dou, Q P


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a485735.pdf


Report Date : Mar 2008


Pagination or Media Count : 83


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 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 protein(s) 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 N1 ring substituents, and evaluated their potencies to inhibit proliferation and induce apoptosis in human breast cancer cells. We have also studied the biochemical targets of these b-lactams by performing microarray assay. Our results supported by this IDEA 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.


Descriptors :   *BREAST CANCER , *ANTIBIOTICS , *APOPTOSIS , *PREVENTIVE MEDICINE , *INFECTIOUS DISEASES , *BACTERIAL DISEASES , *CELLS(BIOLOGY) , CHEMOTHERAPY , POTENCY , DRUGS , DEOXYRIBONUCLEIC ACIDS , NEOPLASMS , SYNTHESIS(CHEMISTRY) , BIOCHEMISTRY , DAMAGE , TOXICITY


Subject Categories : Biochemistry
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE