title: Anti-tumor activity of N-thiolated beta-lactam antibiotics.
abstract: An ongoing strategy for cancer treatment is selective induction of apoptosis in cancer over normal cells. N-thiolated beta-lactams were found to induce DNA damage, growth arrest and apoptosis in cultured human cancer cells. However, whether these compounds have a similar effect in vivo has not been studied. We report here that treatment with the beta-lactam L-1 caused a significant inhibition of tumor growth in a breast cancer xenograft mouse model, associated with induction of DNA damage and apoptosis in vivo. These results suggest that the synthetic antibiotic N-thiolated beta-lactams hold great potential to be developed as novel anti-cancer drugs.
authors.affiliation: The Prevention Program, Barbara Ann Karmanos Cancer Institute, Department of Pathology, School of Medicine, Wayne State University, 540.1 HWCRC, 4100 John R Road, Detroit, MI 48201, USA.
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Falsetti
authors.forename: Michael
authors.initials: M
authors.lastname: Frezza
authors.forename: Vesna
authors.initials: V
authors.lastname: Milacic
authors.forename: Aslamuzzaman
authors.initials: A
authors.lastname: Kazi
authors.forename: Qiuzhi Cindy
authors.initials: QC
authors.lastname: Cui
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Long
authors.forename: Edward
authors.initials: E
authors.lastname: Turos
authors.forename: Q Ping
authors.initials: QP
authors.lastname: Dou
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000943:Antigens, Differentiation / Q000378:metabolism; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy*; D004249:DNA Damage; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008819:Mice, Nude; D008997:Monobactams / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D000097642:GADD45 Proteins
chemical_list: D000900:Anti-Bacterial Agents; D000943:Antigens, Differentiation; D018840:HSP70 Heat-Shock Proteins; D008997:Monobactams; C086470:GADD45B protein, human; D000097642:GADD45 Proteins