title: Antitumor Activity of 2,9-Di-Sec-Butyl-1,10-Phenanthroline.
abstract: The anti-tumor effect of a chelating phen-based ligand 2,9-di-sec-butyl-1,10-phenanthroline (dsBPT) and its combination with cisplatin were examined in both lung and head and neck cancer cell lines and xenograft animal models in this study. The effects of this agent on cell cycle and apoptosis were investigated. Protein markers relevant to these mechanisms were also assessed. We found that the inhibitory effect of dsBPT on lung and head and neck cancer cell growth (IC50 ranged between 0.1-0.2 μM) was 10 times greater than that on normal epithelial cells. dsBPT alone induced autophagy, G1 cell cycle arrest, and apoptosis. Our in vivo studies indicated that dsBPT inhibited tumor growth in a dose-dependent manner in a head and neck cancer xenograft mouse model. The combination of dsBPT with cisplatin synergistically inhibited cancer cell growth with a combination index of 0.3. Moreover, the combination significantly reduced tumor volume as compared with the untreated control (p = 0.0017) in a head and neck cancer xenograft model. No organ related toxicities were observed in treated animals. Our data suggest that dsBPT is a novel and potent antitumor drug that warrants further preclinical and clinical development either as a single agent or in combination with known chemotherapy drugs such as cisplatin.
authors.affiliation: Department of Hematology and Medicinal Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, United States of America.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Hematology and Medicinal Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, United States of America.
authors.forename: Shifang
authors.initials: S
authors.lastname: Peng
authors.affiliation: Department of Hematology and Medicinal Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, United States of America.
authors.forename: A R M Ruhul
authors.initials: AR
authors.lastname: Amin
authors.affiliation: Department of Hematology and Medicinal Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, United States of America.
authors.forename: Mohammad Aminur
authors.initials: MA
authors.lastname: Rahman
authors.affiliation: Department of Hematology and Medicinal Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, United States of America.
authors.forename: Sreenivas
authors.initials: S
authors.lastname: Nannapaneni
authors.affiliation: Department of Biostatistics and Bioinformatics, Biostatistics and Bioinformatics Shared Resource at WCI, NE, Atlanta, GA, United States of America.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Hematology and Medicinal Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, United States of America.
authors.forename: Dong M
authors.initials: DM
authors.lastname: Shin
authors.affiliation: Department of Hematology and Medicinal Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, United States of America.
authors.forename: Nabil F
authors.initials: NF
authors.lastname: Saba
authors.affiliation: Department of Chemistry, University of California-Riverside, Riverside, CA, United States of America.
authors.forename: Jack F
authors.initials: JF
authors.lastname: Eichler
authors.affiliation: Department of Hematology and Medicinal Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, United States of America.
authors.forename: Zhuo G
authors.initials: ZG
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004357:Drug Synergism; D006258:Head and Neck Neoplasms / Q000473:pathology; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D010618:Phenanthrolines / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: C000621264:2,9-di-sec-butyl-1,10-phenanthroline; D000970:Antineoplastic Agents; D010618:Phenanthrolines; D002945:Cisplatin; C025205:1,10-phenanthroline